The use of positron emitter-labeled compounds for somatostatin receptor imaging (SRI) has become ... more The use of positron emitter-labeled compounds for somatostatin receptor imaging (SRI) has become attractive because of the prospect of improved spatial resolution, accelerated imaging procedures, and the ability to quantify tissue radioactivity concentrations. This paper provides results from first-in-humans use of 64 Cu-DOTATATE, an avidly binding somatostatin receptor ligand linked to a radioisotope with intermediate half-life and favorable positron energy (half-life, 12.7 h; maximum positron energy, 0.653 MeV). Methods: In a prospective setup, 14 patients with a history of neuroendocrine tumors underwent both PET/CT with 64 Cu-DOTATATE and SPECT/CT with our current routine imaging agent 111 In-diethylenetriaminepentaacetic acid-octreotide. After intravenous injection of 193-232 MBq of 64 Cu-DOTATATE, whole-body PET scans were acquired at 1 h (n 5 14), 3 h (n 5 12), and 24 h (n 5 5) after administration. Tissue radioactivity concentrations for normal organs and lesions were quantified, and standardized uptake values were calculated for the early (1 h) and delayed (3 h) scans. Using the data for 5 patients, we assessed the radiation dose with OLINDA/EXM software. Furthermore, the clinical performance of 64 Cu-DOTATATE with respect to lesion detection was compared with conventional SRI. Results: SRI with 64 Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3 h. Compared with conventional scintigraphy, 64 Cu-DOTATATE PET identified additional lesions in 6 of 14 patients (43%). In 5 patients, lesions were localized in organs and organ systems not previously known as metastatic sites, including the early-stage detection of a secondary neuroendocrine tumor in a patient with a known mutation in the multiple endocrine neoplasia type I gene. All major additional findings seen only on PET could be confirmed on the basis of a clinical follow-up interval of 18 mo. Calculated radiation dose estimates yielded an effective dose of 6.3 mSv for an injected activity of 200 MBq of 64 Cu-DOTATATE, with the liver being the organ with the highest absorbed radiation dose (0.16 mGy/MBq). Conclusion: This first-in-humans study supports the clinical use of 64 Cu-DOTATATE for SRI with excellent imaging quality, reduced radiation burden, and increased lesion detection rate when compared with 111 In-diethylenetriaminepentaacetic acid-octreotide.
Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to c... more Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with 111 In-diethylenetriaminepentaacetic acidoctreotide, scintigraphy with 123 I-metaiodobenzylguanidine (MIBG), and 18 F-FDG PET. Methods: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, 123 I-MIBG scintigraphy, and 18 F-FDG PET on average within 40 d. The functional images were fused with low-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. Results: The overall sensitivity of SRS, 123 I-MIBG scintigraphy, and 18 F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were 18 F-FDG PET-positive, of which 3 were also 123 I-MIBG scintigraphypositive, giving a combined overall sensitivity of 96%. SRS also exceeded 123 I-MIBG scintigraphy and 18 F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. 123 I-MIBG scintigraphy was superior to 18 F-FDG PET for ileal neuroendocrine tumors, and 18 F-FDG PET was superior to 123 I-MIBG scintigraphy for pancreaticoduodenal neuroendocrine tumors. The sensitivity of 18 F-FDG PET (92%) exceeded that of both SRS (69%) and 123 I-MIBG scintigraphy (46%) for tumors with a proliferation index above 15%. Conclusion: The overall sensitivity of 123 I-MIBG scintigraphy and 18 F-FDG PET was low compared with SRS. However, for tumors with a high proliferation rate, 18 F-FDG PET had the highest sensitivity. The results indicate that, although SRS should still be the routine method, 18 F-FDG PET provides complementary diagnostic information and is of value for neuroendocrine tumor patients with negative SRS findings or a high proliferation index.
Introduction: Lymph node yield (LNY) in neck dissection has been identified as a prognostic facto... more Introduction: Lymph node yield (LNY) in neck dissection has been identified as a prognostic factor in oral cavity cancer. The purpose of this study was to investigate the impact of additional use of optical imaging on LNY in therapeutic ND in oral cancer. Methods: Consecutive patients with oral squamous cell carcinoma with clinical neck metastasis planned for primary tumor resection were randomized to conventional neck dissection or near-infrared fluorescence (NIRF)-guided neck dissection, respectively. In the intervention group, patients were injected with ICG-Nanocoll prior to surgery. Intraoperatively, an optical hand-held camera system was used for lymph node identification. Also, NIRF imaging of the neck specimen was performed, and optical signals were pinned with needle markings to guide the pathological examination. The endpoint of the study was LNY per neck side in levels Ib-III. Results: 31 patients were included with 18 neck sides in the control group and 18 neck sides in the intervention group for evaluation. During NIRF-guided ND, individual lymph nodes could be identified by a bright fluorescent signal and individual tumor-related drainage patterns could be observed in the neck. The LNY in the intervention group was significantly higher compared to the control group (p ¼ 0.032) with a mean of 24 LN (range: 12e33 LN in levels Ib-III compared to 18 LN (range: 10e36 LN) in the control group, respectively. Conclusions: NIRF-guided ND significantly improved the nodal yield compared to the control group. Intraoperative real-time optical imaging enabled direct visualization of tumor-related drainage patterns within the neck lymphatics.
The authors describe the diagnostic use of I-123 MIBG scintigraphy in a 61-year-old man who was t... more The authors describe the diagnostic use of I-123 MIBG scintigraphy in a 61-year-old man who was thought to have a recurrence 25 years after a left adrenalectomy for a pheochromocytoma. Preoperative I-123 MIBG scintigraphy was performed twice along with intraoperative gamma probe localization of the lesions. The preoperative MIBG scintigraphy revealed three pathologic processes in the upper left abdomen, whereas computed tomographic scanning identified only one site of involvement. All three metastatic lesions were removed successfully with the aid of a gamma probe. Preoperative I-123 MIBG scintigraphy, combined with intraoperative gamma probe identification of I-123 MIBG foci, is feasible and a valuable tool to detect malignant masses possibly overlooked by other imaging techniques.
International Journal of Cardiovascular Imaging, Jan 3, 2017
Background: The extra-cardiac work-up in infective endocarditis (IE) is comprises a search for bo... more Background: The extra-cardiac work-up in infective endocarditis (IE) is comprises a search for both primary and secondary infective foci. Whether 18F-FDG PET/CT (PET/CT) or 99mTc-HMPAO white blood cell SPECT/CT (SPECT/CT) is superior in detection of extra-cardiac manifestations in IE is unexplored. The purposes of the study were: (1) to identify the numbers of positive findings detected by each imaging modality, (2) to evaluate the clinical utility of these findings and (3) to define the reproducibility of PET/CT and SPECT/CT for extracardiac foci in patients diagnosed with Duke Definite IE. Methods: Each imaging modality was evaluated for numbers and location of positive extra-cardiac foci in patients with Duke definite IE. A team of 2x2 cardiologists carefully evaluated each positive finding to determine clinical utility for each individual patient. Clinical utility was determined by 4 criteria converted into an ordinal scale with values from 0 to 4; (1) Findings identified were not found by traditional imaging modalities; (2) Findings implicated treatment choice or duration of treatment; (3) Findings prompted further investigation with novel clinical findings or (4) foci found were silent lesions. Using the focus with highest clinical utility rating in each patient, the clinical impact of the two imaging modalities was expressed in a clinical utility score. Further, to evaluate reproducibility for SPECT/CT and PET/CT, an imaging core laboratory reviewed the findings of each imaging modality. Results: In 55 IE patients, 91 pathological foci were found by PET/CT and 37 foci were identified by SPECT/CT (p<0.001). The clinical utility of PET/CT was significantly higher than that of SPECT/CT when comparing the clinical utility score (1.71 vs. 0.89, p<0.01). In assessment of extra-cardiac diagnostics in IE, inter-observer reproducibility was substantial for SPECT/CT with a weighted kappa of 0.69 (95%CI 0.49-0.89) and substantial to excellent for PET/CT with a weighted kappa of 0.79 (95%CI 0.61-0.98). Conclusions: PET/CT has a significantly higher clinical utility score than SPECT/CT and is potentially advantageous to SPECT/CT in detection of extra-cardiac pathology in patients with IE.
The aim of this study was to investigate the prognostic value of the quantitative assessment of s... more The aim of this study was to investigate the prognostic value of the quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index [BSI]) in patients who have advanced metastatic castration-resistant prostate cancer (mCRPC) and are receiving 223 RaCl 2. We hypothesized that the BSI can serve as a prognostic biomarker of overall survival (OS) and hematologic toxicity and as a tool for response assessment in patients with mCRPC treated with 223 RaCl 2. Methods: This study was a retrospective investigation of a Danish cohort of mCRPC patients who received 223 RaCl 2 therapy between March 2014 and October 2015 and for whom baseline bone scintigraphy was available. Bone scintigraphy studies were reviewed and graded according to the extent of disease. Furthermore, an automated BSI (EXINI Bone BSI) was obtained for baseline scintigraphy studies and follow-up scans after 3 cycles as well as at the end of therapy. Clinical outcomes were OS and occurrence of hematologic toxicity of grades 2-5. Associations between the BSI and clinical outcomes were investigated in multivariate regression models including the visual assessment of bone scintigraphy and other relevant covariates. Results: A total of 88 patients were included. The median number of completed 223 RaCl 2 cycles was 4, and 27 patients (31%) completed 6 cycles. The BSI was significantly associated with OS in the multivariate analysis; the median OS for patients with a BSI of greater than 5 was 8.2 mo, and the median OS for patients with a BSI of less than or equal to 5 was 15.0 mo (hazard ratio, 2.65 [95% confidence interval, 1.5-4.71]; P 5 0.001). Likewise, the baseline BSI was prognostic for the occurrence of hematologic toxicity; patients with a BSI of greater than 5 had an odds ratio of 3.02 (95% confidence interval, 1.2-7.8; P 5 0.02) for toxicity. The BSI declined during therapy in 44% of the patients who completed 3 cycles of 223 RaCl 2 (n 5 52) and in 84% of the patients after the end of therapy (n 5 32). There was no significant association between a change in the BSI during therapy and OS. Conclusion: The BSI is a promising biomarker for prognostication of OS and hematologic toxicity in late-stage mCRPC patients receiving 223 RaCl 2. Further prospective studies are needed to evaluate the potential of the BSI for response assessment in 223 RaCl 2 therapy.
American Journal of Respiratory and Critical Care Medicine, Mar 1, 2016
Rationale: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been foll... more Rationale: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. Objectives: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. Methods: A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). Measurements and Main Results: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P , 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P , 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P , 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. Conclusions: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).
Hyperthermic isolated limb perfusion (HILP) is an effective method in the treatment of recurrent ... more Hyperthermic isolated limb perfusion (HILP) is an effective method in the treatment of recurrent melanomas and soft tissue sarcomas. To avoid systemic toxicity, leakage from the limb perfusate into the systemic circulation is real-time monitored by administration of a radioactive agent to the limb circuit. This has made HILP safe for the patient. However, the radiation exposure to the surgical staff has never been measured and could be a limiting factor for the use of HILP. The purpose of the present study was to measure and evaluate the radiation exposure to the surgical staff performing HILP with (99m)Technetium labeled red blood cells. Thirteen patients had HILP performed in 11 lower limbs and two upper limbs at our inpatient clinic between October 2006 and February 2007. The surgeon and nurse had thermoluminescence dosimetry (TLD) chips attached to the finger pulp and to the ring area of the left fourth finger, as well as an electronic dosimeter attached to the anterior lining of the trousers. The anesthesiologist and perfusion technologist also carried electronic dosimeters. The surgeon had the highest radioactive exposure with an average dose per procedure to the finger pulp of 16.2 microSv, to the ring area of 8.5 microSv, and to the abdominal wall of 4.2 +/- 0.6 microSv. HILP with (99m)technetium-labeled red blood cells does not constitute a safety risk to the operating team with respect to radioactive exposure. Routine dose monitoring of the staff or special precautions for fertile women are not necessary.
Accurate grading of patients with neuroendocrine neoplasms (NENs) is essential for risk stratific... more Accurate grading of patients with neuroendocrine neoplasms (NENs) is essential for risk stratification and optimal choice of therapy. Currently, grading is based on histologically assessed degree of tumor proliferation. The aim of the present study was to assess the long-term prognostic value of 18 F-FDG PET imaging for risk stratification of NENs and compare it with tumor grading (World Health Organization 2010 classification). Methods: We conducted a prospective cohort study evaluating the prognostic value of 18 F-FDG PET imaging and compared it with histologic grading. Enrolled were 166 patients of all grades and with histologically confirmed NENs of gastroenteropancreatic origin. The primary endpoint was overall survival (OS). Progression-free survival (PFS) was a secondary endpoint. In addition, OS in relation to peptide receptor radionuclide therapy (PRRT) was analyzed as an exploratory endpoint. The median follow-up time was 9.8 y. Results: Analysis of the whole cohort revealed that a positive 18 F-FDG PET scan was associated with a shorter OS than a negative 18 F-FDG PET scan (hazard ratio: 3.8; 95% CI: 2.4-5.9; P , 0.001). In G1 and G2 patients (n 5 140), a positive 18 F-FDG PET scan was the only identifier of high risk for death (hazard ratio: 3.6; 95% CI, 2.2-5.9; P , 0.001).
Clinical Physiology and Functional Imaging, Mar 11, 2012
To investigate the development of lung function in HIV-infected patients. In a prospective cohort... more To investigate the development of lung function in HIV-infected patients. In a prospective cohort study, 88 HIV-infected patients had a lung function test performed and 63 patients (72%) had their LFT repeated with a median follow-up period of 4.4 years. Forty-eight per cent were smokers, and at the re-examination, 97% were on combination antiretroviral therapy. Carbon monoxide diffusion capacity was reduced and decreased over time in both smokers and non-smokers. Alveolar volume decreased and forced vital capacity increased similarly in both smokers and non-smokers. No changes were observed in forced expiratory volume or peak flow, but smokers had reduced values compared with those of the non-smokers at both examinations. FEV1/FVC was reduced especially in smokers and declined in both smokers and non-smokers. Carbon monoxide diffusion capacity is reduced in HIV-infected patients and seems to decline over time. Additionally, signs of obstructive lung disease are present in HIV-infected patients and seem to increase over time, although only modestly.
Background: Indeterminate lung nodules detected during lung cancer screening with low dose comput... more Background: Indeterminate lung nodules detected during lung cancer screening with low dose computed tomography (CT) present a challenge in distinguishing between malignant and benign disease. Our aim for this study is to compare the sensitivity and specificity of flourdeoxy-glucose positron emission tomography (FDG-PET), volume doubling time (VDT) and a combination of both in the diagnostic workup of indeterminate lung nodules in lung cancer screening. Method: The Danish Lung Cancer Screening Trial (DLCST) is a randomized controlled trial with heavy smokers between 50-70 years of age. The screening group underwent 5 annual rounds with low dose CT scan of the thorax. When a lung nodule was detected, participants could either be referred to diagnostic workup, 3-month follow-up or continue with the screening program. We included participants who had a 3-month followup scan. Before the follow-up scan was conducted, the participants received a FDG-PET scan. Nodules that were resected or stable for at least 2 years were included. FDG-uptake was categorized from most likely benign (uptake less than background uptake in the mediastinum) to most likely malignant (uptake as mediastinum or higher). VDT was calculated from nodule volume measurements from two time points closest to the FDG-PET scan date. We used a commercially available and validated semi-automated nodule evaluation software. Based on VDT the nodules were divided into three groups. Regressing nodules (VDT<0), slow growing nodules (VDT >365 days-less likely malignant) and fastgrowing nodules (VDT <365 days e most likely malignant). Finally, we divided combined outcome into three groups: 1. Both tests suggest benignancy, 2. One of the tests suggest malignancy and 3. Both tests suggest malignancy. We used receiver operating characteristic (ROC) curves to compare sensitivity and specificity for the ability to predict a malignant or benign nodule. Result: A total of 87 lung nodules in 76 individuals were included. 68/87 (78%) were solid nodules. 41.5% were malignant. Nodule size ranged between 5 mm e 20 mm in largest diameter. The sensitivity and specificity of VDT alone were 61% and 90% respectively. For FDG-PET the sensitivity was 62% and specificity was 90%. Combined use of both tests showed an improvement in test sensitivity to 82% and a specificity of 79%. Conclusion: Combined use of FDG-PET and VDT is recommended in the diagnostic workup of indeterminate lung nodules in lung cancer screening.
Journal of the American College of Cardiology, Apr 1, 2016
Background: The extra-cardiac work-up in infective endocarditis (IE) is comprises a search for bo... more Background: The extra-cardiac work-up in infective endocarditis (IE) is comprises a search for both primary and secondary infective foci. Whether 18F-FDG PET/CT (PET/CT) or 99mTc-HMPAO white blood cell SPECT/CT (SPECT/CT) is superior in detection of extra-cardiac manifestations in IE is unexplored. The purposes of the study were: (1) to identify the numbers of positive findings detected by each imaging modality, (2) to evaluate the clinical utility of these findings and (3) to define the reproducibility of PET/CT and SPECT/CT for extracardiac foci in patients diagnosed with Duke Definite IE. Methods: Each imaging modality was evaluated for numbers and location of positive extra-cardiac foci in patients with Duke definite IE. A team of 2x2 cardiologists carefully evaluated each positive finding to determine clinical utility for each individual patient. Clinical utility was determined by 4 criteria converted into an ordinal scale with values from 0 to 4; (1) Findings identified were not found by traditional imaging modalities; (2) Findings implicated treatment choice or duration of treatment; (3) Findings prompted further investigation with novel clinical findings or (4) foci found were silent lesions. Using the focus with highest clinical utility rating in each patient, the clinical impact of the two imaging modalities was expressed in a clinical utility score. Further, to evaluate reproducibility for SPECT/CT and PET/CT, an imaging core laboratory reviewed the findings of each imaging modality. Results: In 55 IE patients, 91 pathological foci were found by PET/CT and 37 foci were identified by SPECT/CT (p<0.001). The clinical utility of PET/CT was significantly higher than that of SPECT/CT when comparing the clinical utility score (1.71 vs. 0.89, p<0.01). In assessment of extra-cardiac diagnostics in IE, inter-observer reproducibility was substantial for SPECT/CT with a weighted kappa of 0.69 (95%CI 0.49-0.89) and substantial to excellent for PET/CT with a weighted kappa of 0.79 (95%CI 0.61-0.98). Conclusions: PET/CT has a significantly higher clinical utility score than SPECT/CT and is potentially advantageous to SPECT/CT in detection of extra-cardiac pathology in patients with IE.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Purpose The purpose was to investigate the diagnostic performance of bimodal optical and radio-gu... more Purpose The purpose was to investigate the diagnostic performance of bimodal optical and radio-guided sentinel node biopsy (SNB) for oral squamous cell carcinoma (OSCC) sub-sites in the anterior oral cavity. Methods Prospective study of 50 consecutive patients with cN0 OSCC scheduled for SNB was injected with the tracer complex Tc99m:ICG:Nacocoll. A near-infrared camera was applied for optical SN detection. Endpoints were modality for intraoperative SN detection and false omission rate at follow-up. Results In all patients, a SN could be detected. In 12/50 (24%) of cases, the SPECT/CT showed no focus in level 1, but intraoperatively a SN in level 1 was optically detected. In 22/50 cases (44%), an additional SN was identified only due to the optical imaging. At follow-up, the false omission rate was 0%. Conclusion Optical imaging appears to be an effective tool to allow real-time SN identification comprising level 1 unaffected by possible interference of radiation site from the injec...
The use of positron emitter-labeled compounds for somatostatin receptor imaging (SRI) has become ... more The use of positron emitter-labeled compounds for somatostatin receptor imaging (SRI) has become attractive because of the prospect of improved spatial resolution, accelerated imaging procedures, and the ability to quantify tissue radioactivity concentrations. This paper provides results from first-in-humans use of 64 Cu-DOTATATE, an avidly binding somatostatin receptor ligand linked to a radioisotope with intermediate half-life and favorable positron energy (half-life, 12.7 h; maximum positron energy, 0.653 MeV). Methods: In a prospective setup, 14 patients with a history of neuroendocrine tumors underwent both PET/CT with 64 Cu-DOTATATE and SPECT/CT with our current routine imaging agent 111 In-diethylenetriaminepentaacetic acid-octreotide. After intravenous injection of 193-232 MBq of 64 Cu-DOTATATE, whole-body PET scans were acquired at 1 h (n 5 14), 3 h (n 5 12), and 24 h (n 5 5) after administration. Tissue radioactivity concentrations for normal organs and lesions were quantified, and standardized uptake values were calculated for the early (1 h) and delayed (3 h) scans. Using the data for 5 patients, we assessed the radiation dose with OLINDA/EXM software. Furthermore, the clinical performance of 64 Cu-DOTATATE with respect to lesion detection was compared with conventional SRI. Results: SRI with 64 Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3 h. Compared with conventional scintigraphy, 64 Cu-DOTATATE PET identified additional lesions in 6 of 14 patients (43%). In 5 patients, lesions were localized in organs and organ systems not previously known as metastatic sites, including the early-stage detection of a secondary neuroendocrine tumor in a patient with a known mutation in the multiple endocrine neoplasia type I gene. All major additional findings seen only on PET could be confirmed on the basis of a clinical follow-up interval of 18 mo. Calculated radiation dose estimates yielded an effective dose of 6.3 mSv for an injected activity of 200 MBq of 64 Cu-DOTATATE, with the liver being the organ with the highest absorbed radiation dose (0.16 mGy/MBq). Conclusion: This first-in-humans study supports the clinical use of 64 Cu-DOTATATE for SRI with excellent imaging quality, reduced radiation burden, and increased lesion detection rate when compared with 111 In-diethylenetriaminepentaacetic acid-octreotide.
Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to c... more Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with 111 In-diethylenetriaminepentaacetic acidoctreotide, scintigraphy with 123 I-metaiodobenzylguanidine (MIBG), and 18 F-FDG PET. Methods: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, 123 I-MIBG scintigraphy, and 18 F-FDG PET on average within 40 d. The functional images were fused with low-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. Results: The overall sensitivity of SRS, 123 I-MIBG scintigraphy, and 18 F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were 18 F-FDG PET-positive, of which 3 were also 123 I-MIBG scintigraphypositive, giving a combined overall sensitivity of 96%. SRS also exceeded 123 I-MIBG scintigraphy and 18 F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. 123 I-MIBG scintigraphy was superior to 18 F-FDG PET for ileal neuroendocrine tumors, and 18 F-FDG PET was superior to 123 I-MIBG scintigraphy for pancreaticoduodenal neuroendocrine tumors. The sensitivity of 18 F-FDG PET (92%) exceeded that of both SRS (69%) and 123 I-MIBG scintigraphy (46%) for tumors with a proliferation index above 15%. Conclusion: The overall sensitivity of 123 I-MIBG scintigraphy and 18 F-FDG PET was low compared with SRS. However, for tumors with a high proliferation rate, 18 F-FDG PET had the highest sensitivity. The results indicate that, although SRS should still be the routine method, 18 F-FDG PET provides complementary diagnostic information and is of value for neuroendocrine tumor patients with negative SRS findings or a high proliferation index.
Introduction: Lymph node yield (LNY) in neck dissection has been identified as a prognostic facto... more Introduction: Lymph node yield (LNY) in neck dissection has been identified as a prognostic factor in oral cavity cancer. The purpose of this study was to investigate the impact of additional use of optical imaging on LNY in therapeutic ND in oral cancer. Methods: Consecutive patients with oral squamous cell carcinoma with clinical neck metastasis planned for primary tumor resection were randomized to conventional neck dissection or near-infrared fluorescence (NIRF)-guided neck dissection, respectively. In the intervention group, patients were injected with ICG-Nanocoll prior to surgery. Intraoperatively, an optical hand-held camera system was used for lymph node identification. Also, NIRF imaging of the neck specimen was performed, and optical signals were pinned with needle markings to guide the pathological examination. The endpoint of the study was LNY per neck side in levels Ib-III. Results: 31 patients were included with 18 neck sides in the control group and 18 neck sides in the intervention group for evaluation. During NIRF-guided ND, individual lymph nodes could be identified by a bright fluorescent signal and individual tumor-related drainage patterns could be observed in the neck. The LNY in the intervention group was significantly higher compared to the control group (p ¼ 0.032) with a mean of 24 LN (range: 12e33 LN in levels Ib-III compared to 18 LN (range: 10e36 LN) in the control group, respectively. Conclusions: NIRF-guided ND significantly improved the nodal yield compared to the control group. Intraoperative real-time optical imaging enabled direct visualization of tumor-related drainage patterns within the neck lymphatics.
The authors describe the diagnostic use of I-123 MIBG scintigraphy in a 61-year-old man who was t... more The authors describe the diagnostic use of I-123 MIBG scintigraphy in a 61-year-old man who was thought to have a recurrence 25 years after a left adrenalectomy for a pheochromocytoma. Preoperative I-123 MIBG scintigraphy was performed twice along with intraoperative gamma probe localization of the lesions. The preoperative MIBG scintigraphy revealed three pathologic processes in the upper left abdomen, whereas computed tomographic scanning identified only one site of involvement. All three metastatic lesions were removed successfully with the aid of a gamma probe. Preoperative I-123 MIBG scintigraphy, combined with intraoperative gamma probe identification of I-123 MIBG foci, is feasible and a valuable tool to detect malignant masses possibly overlooked by other imaging techniques.
International Journal of Cardiovascular Imaging, Jan 3, 2017
Background: The extra-cardiac work-up in infective endocarditis (IE) is comprises a search for bo... more Background: The extra-cardiac work-up in infective endocarditis (IE) is comprises a search for both primary and secondary infective foci. Whether 18F-FDG PET/CT (PET/CT) or 99mTc-HMPAO white blood cell SPECT/CT (SPECT/CT) is superior in detection of extra-cardiac manifestations in IE is unexplored. The purposes of the study were: (1) to identify the numbers of positive findings detected by each imaging modality, (2) to evaluate the clinical utility of these findings and (3) to define the reproducibility of PET/CT and SPECT/CT for extracardiac foci in patients diagnosed with Duke Definite IE. Methods: Each imaging modality was evaluated for numbers and location of positive extra-cardiac foci in patients with Duke definite IE. A team of 2x2 cardiologists carefully evaluated each positive finding to determine clinical utility for each individual patient. Clinical utility was determined by 4 criteria converted into an ordinal scale with values from 0 to 4; (1) Findings identified were not found by traditional imaging modalities; (2) Findings implicated treatment choice or duration of treatment; (3) Findings prompted further investigation with novel clinical findings or (4) foci found were silent lesions. Using the focus with highest clinical utility rating in each patient, the clinical impact of the two imaging modalities was expressed in a clinical utility score. Further, to evaluate reproducibility for SPECT/CT and PET/CT, an imaging core laboratory reviewed the findings of each imaging modality. Results: In 55 IE patients, 91 pathological foci were found by PET/CT and 37 foci were identified by SPECT/CT (p<0.001). The clinical utility of PET/CT was significantly higher than that of SPECT/CT when comparing the clinical utility score (1.71 vs. 0.89, p<0.01). In assessment of extra-cardiac diagnostics in IE, inter-observer reproducibility was substantial for SPECT/CT with a weighted kappa of 0.69 (95%CI 0.49-0.89) and substantial to excellent for PET/CT with a weighted kappa of 0.79 (95%CI 0.61-0.98). Conclusions: PET/CT has a significantly higher clinical utility score than SPECT/CT and is potentially advantageous to SPECT/CT in detection of extra-cardiac pathology in patients with IE.
The aim of this study was to investigate the prognostic value of the quantitative assessment of s... more The aim of this study was to investigate the prognostic value of the quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index [BSI]) in patients who have advanced metastatic castration-resistant prostate cancer (mCRPC) and are receiving 223 RaCl 2. We hypothesized that the BSI can serve as a prognostic biomarker of overall survival (OS) and hematologic toxicity and as a tool for response assessment in patients with mCRPC treated with 223 RaCl 2. Methods: This study was a retrospective investigation of a Danish cohort of mCRPC patients who received 223 RaCl 2 therapy between March 2014 and October 2015 and for whom baseline bone scintigraphy was available. Bone scintigraphy studies were reviewed and graded according to the extent of disease. Furthermore, an automated BSI (EXINI Bone BSI) was obtained for baseline scintigraphy studies and follow-up scans after 3 cycles as well as at the end of therapy. Clinical outcomes were OS and occurrence of hematologic toxicity of grades 2-5. Associations between the BSI and clinical outcomes were investigated in multivariate regression models including the visual assessment of bone scintigraphy and other relevant covariates. Results: A total of 88 patients were included. The median number of completed 223 RaCl 2 cycles was 4, and 27 patients (31%) completed 6 cycles. The BSI was significantly associated with OS in the multivariate analysis; the median OS for patients with a BSI of greater than 5 was 8.2 mo, and the median OS for patients with a BSI of less than or equal to 5 was 15.0 mo (hazard ratio, 2.65 [95% confidence interval, 1.5-4.71]; P 5 0.001). Likewise, the baseline BSI was prognostic for the occurrence of hematologic toxicity; patients with a BSI of greater than 5 had an odds ratio of 3.02 (95% confidence interval, 1.2-7.8; P 5 0.02) for toxicity. The BSI declined during therapy in 44% of the patients who completed 3 cycles of 223 RaCl 2 (n 5 52) and in 84% of the patients after the end of therapy (n 5 32). There was no significant association between a change in the BSI during therapy and OS. Conclusion: The BSI is a promising biomarker for prognostication of OS and hematologic toxicity in late-stage mCRPC patients receiving 223 RaCl 2. Further prospective studies are needed to evaluate the potential of the BSI for response assessment in 223 RaCl 2 therapy.
American Journal of Respiratory and Critical Care Medicine, Mar 1, 2016
Rationale: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been foll... more Rationale: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. Objectives: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. Methods: A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). Measurements and Main Results: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P , 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P , 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P , 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. Conclusions: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).
Hyperthermic isolated limb perfusion (HILP) is an effective method in the treatment of recurrent ... more Hyperthermic isolated limb perfusion (HILP) is an effective method in the treatment of recurrent melanomas and soft tissue sarcomas. To avoid systemic toxicity, leakage from the limb perfusate into the systemic circulation is real-time monitored by administration of a radioactive agent to the limb circuit. This has made HILP safe for the patient. However, the radiation exposure to the surgical staff has never been measured and could be a limiting factor for the use of HILP. The purpose of the present study was to measure and evaluate the radiation exposure to the surgical staff performing HILP with (99m)Technetium labeled red blood cells. Thirteen patients had HILP performed in 11 lower limbs and two upper limbs at our inpatient clinic between October 2006 and February 2007. The surgeon and nurse had thermoluminescence dosimetry (TLD) chips attached to the finger pulp and to the ring area of the left fourth finger, as well as an electronic dosimeter attached to the anterior lining of the trousers. The anesthesiologist and perfusion technologist also carried electronic dosimeters. The surgeon had the highest radioactive exposure with an average dose per procedure to the finger pulp of 16.2 microSv, to the ring area of 8.5 microSv, and to the abdominal wall of 4.2 +/- 0.6 microSv. HILP with (99m)technetium-labeled red blood cells does not constitute a safety risk to the operating team with respect to radioactive exposure. Routine dose monitoring of the staff or special precautions for fertile women are not necessary.
Accurate grading of patients with neuroendocrine neoplasms (NENs) is essential for risk stratific... more Accurate grading of patients with neuroendocrine neoplasms (NENs) is essential for risk stratification and optimal choice of therapy. Currently, grading is based on histologically assessed degree of tumor proliferation. The aim of the present study was to assess the long-term prognostic value of 18 F-FDG PET imaging for risk stratification of NENs and compare it with tumor grading (World Health Organization 2010 classification). Methods: We conducted a prospective cohort study evaluating the prognostic value of 18 F-FDG PET imaging and compared it with histologic grading. Enrolled were 166 patients of all grades and with histologically confirmed NENs of gastroenteropancreatic origin. The primary endpoint was overall survival (OS). Progression-free survival (PFS) was a secondary endpoint. In addition, OS in relation to peptide receptor radionuclide therapy (PRRT) was analyzed as an exploratory endpoint. The median follow-up time was 9.8 y. Results: Analysis of the whole cohort revealed that a positive 18 F-FDG PET scan was associated with a shorter OS than a negative 18 F-FDG PET scan (hazard ratio: 3.8; 95% CI: 2.4-5.9; P , 0.001). In G1 and G2 patients (n 5 140), a positive 18 F-FDG PET scan was the only identifier of high risk for death (hazard ratio: 3.6; 95% CI, 2.2-5.9; P , 0.001).
Clinical Physiology and Functional Imaging, Mar 11, 2012
To investigate the development of lung function in HIV-infected patients. In a prospective cohort... more To investigate the development of lung function in HIV-infected patients. In a prospective cohort study, 88 HIV-infected patients had a lung function test performed and 63 patients (72%) had their LFT repeated with a median follow-up period of 4.4 years. Forty-eight per cent were smokers, and at the re-examination, 97% were on combination antiretroviral therapy. Carbon monoxide diffusion capacity was reduced and decreased over time in both smokers and non-smokers. Alveolar volume decreased and forced vital capacity increased similarly in both smokers and non-smokers. No changes were observed in forced expiratory volume or peak flow, but smokers had reduced values compared with those of the non-smokers at both examinations. FEV1/FVC was reduced especially in smokers and declined in both smokers and non-smokers. Carbon monoxide diffusion capacity is reduced in HIV-infected patients and seems to decline over time. Additionally, signs of obstructive lung disease are present in HIV-infected patients and seem to increase over time, although only modestly.
Background: Indeterminate lung nodules detected during lung cancer screening with low dose comput... more Background: Indeterminate lung nodules detected during lung cancer screening with low dose computed tomography (CT) present a challenge in distinguishing between malignant and benign disease. Our aim for this study is to compare the sensitivity and specificity of flourdeoxy-glucose positron emission tomography (FDG-PET), volume doubling time (VDT) and a combination of both in the diagnostic workup of indeterminate lung nodules in lung cancer screening. Method: The Danish Lung Cancer Screening Trial (DLCST) is a randomized controlled trial with heavy smokers between 50-70 years of age. The screening group underwent 5 annual rounds with low dose CT scan of the thorax. When a lung nodule was detected, participants could either be referred to diagnostic workup, 3-month follow-up or continue with the screening program. We included participants who had a 3-month followup scan. Before the follow-up scan was conducted, the participants received a FDG-PET scan. Nodules that were resected or stable for at least 2 years were included. FDG-uptake was categorized from most likely benign (uptake less than background uptake in the mediastinum) to most likely malignant (uptake as mediastinum or higher). VDT was calculated from nodule volume measurements from two time points closest to the FDG-PET scan date. We used a commercially available and validated semi-automated nodule evaluation software. Based on VDT the nodules were divided into three groups. Regressing nodules (VDT<0), slow growing nodules (VDT >365 days-less likely malignant) and fastgrowing nodules (VDT <365 days e most likely malignant). Finally, we divided combined outcome into three groups: 1. Both tests suggest benignancy, 2. One of the tests suggest malignancy and 3. Both tests suggest malignancy. We used receiver operating characteristic (ROC) curves to compare sensitivity and specificity for the ability to predict a malignant or benign nodule. Result: A total of 87 lung nodules in 76 individuals were included. 68/87 (78%) were solid nodules. 41.5% were malignant. Nodule size ranged between 5 mm e 20 mm in largest diameter. The sensitivity and specificity of VDT alone were 61% and 90% respectively. For FDG-PET the sensitivity was 62% and specificity was 90%. Combined use of both tests showed an improvement in test sensitivity to 82% and a specificity of 79%. Conclusion: Combined use of FDG-PET and VDT is recommended in the diagnostic workup of indeterminate lung nodules in lung cancer screening.
Journal of the American College of Cardiology, Apr 1, 2016
Background: The extra-cardiac work-up in infective endocarditis (IE) is comprises a search for bo... more Background: The extra-cardiac work-up in infective endocarditis (IE) is comprises a search for both primary and secondary infective foci. Whether 18F-FDG PET/CT (PET/CT) or 99mTc-HMPAO white blood cell SPECT/CT (SPECT/CT) is superior in detection of extra-cardiac manifestations in IE is unexplored. The purposes of the study were: (1) to identify the numbers of positive findings detected by each imaging modality, (2) to evaluate the clinical utility of these findings and (3) to define the reproducibility of PET/CT and SPECT/CT for extracardiac foci in patients diagnosed with Duke Definite IE. Methods: Each imaging modality was evaluated for numbers and location of positive extra-cardiac foci in patients with Duke definite IE. A team of 2x2 cardiologists carefully evaluated each positive finding to determine clinical utility for each individual patient. Clinical utility was determined by 4 criteria converted into an ordinal scale with values from 0 to 4; (1) Findings identified were not found by traditional imaging modalities; (2) Findings implicated treatment choice or duration of treatment; (3) Findings prompted further investigation with novel clinical findings or (4) foci found were silent lesions. Using the focus with highest clinical utility rating in each patient, the clinical impact of the two imaging modalities was expressed in a clinical utility score. Further, to evaluate reproducibility for SPECT/CT and PET/CT, an imaging core laboratory reviewed the findings of each imaging modality. Results: In 55 IE patients, 91 pathological foci were found by PET/CT and 37 foci were identified by SPECT/CT (p<0.001). The clinical utility of PET/CT was significantly higher than that of SPECT/CT when comparing the clinical utility score (1.71 vs. 0.89, p<0.01). In assessment of extra-cardiac diagnostics in IE, inter-observer reproducibility was substantial for SPECT/CT with a weighted kappa of 0.69 (95%CI 0.49-0.89) and substantial to excellent for PET/CT with a weighted kappa of 0.79 (95%CI 0.61-0.98). Conclusions: PET/CT has a significantly higher clinical utility score than SPECT/CT and is potentially advantageous to SPECT/CT in detection of extra-cardiac pathology in patients with IE.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Purpose The purpose was to investigate the diagnostic performance of bimodal optical and radio-gu... more Purpose The purpose was to investigate the diagnostic performance of bimodal optical and radio-guided sentinel node biopsy (SNB) for oral squamous cell carcinoma (OSCC) sub-sites in the anterior oral cavity. Methods Prospective study of 50 consecutive patients with cN0 OSCC scheduled for SNB was injected with the tracer complex Tc99m:ICG:Nacocoll. A near-infrared camera was applied for optical SN detection. Endpoints were modality for intraoperative SN detection and false omission rate at follow-up. Results In all patients, a SN could be detected. In 12/50 (24%) of cases, the SPECT/CT showed no focus in level 1, but intraoperatively a SN in level 1 was optically detected. In 22/50 cases (44%), an additional SN was identified only due to the optical imaging. At follow-up, the false omission rate was 0%. Conclusion Optical imaging appears to be an effective tool to allow real-time SN identification comprising level 1 unaffected by possible interference of radiation site from the injec...
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