Papers by L. Melendez-Alafort
Hotel GLI DEI …, 2010
... A Accardo 60 Aime 19, 20, 21, 23 Alessio 15 Alinovi 39 Antonucci 42, 44 Arcovito 18 Ardiccion... more ... A Accardo 60 Aime 19, 20, 21, 23 Alessio 15 Alinovi 39 Antonucci 42, 44 Arcovito 18 Ardiccioni 18 Arena 28 Arnesano 30 Ascenzi 32 B ... 28, 29 Borghi 35 Brun 64 Brunori 18 Burini 38, 55, 57 Buschini 39 C Caccioppola 26 Cai 56 Calò 30 Cantisani 14 Capobianco 44 Carrisi 44 ...
Revista De Investigacion Clinica, 2001
AIP Conference Proceedings, 2003
Recently, antimicrobial peptides have been proposed as new agents to distinguish between bacteria... more Recently, antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. Based on these considerations, Ubiquicidin peptide 29-41 (UBI) has been labeled with 99mTc using a new direct method showing a radiochemical purity > 97 %, high stability in human serum, and low protein binding. In addition 99mTc-UBI showed a specific in vitro
Nuclear Medicine and Biology, 2015
About 90% of insulinomas are benign and 5%-15% are malignant. Benign insulinomas express the gluc... more About 90% of insulinomas are benign and 5%-15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R) and low levels of somatostatin receptors (SSTR), while malignant insulinomas over-express SSTR or GLP-1R in low levels. A kit for the preparation of Lys(27)((99m)Tc-EDDA/HYNIC)-Exendin(9-39)/(99m)Tc-EDDA/HYNIC-Tyr(3)Octreotide was formulated to detect 100% of insulinomas. The formulation showed radiochemical purity of 97±1%, high stability in human serum, and GLP-1R and SSTR affinity. The biodistribution and imaging studies demonstrated properties suitable for its use as a target-specific agent for the simultaneous molecular imaging of GRP-1R- and/or SSTR-positive tumors.
The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), 2003
Radiolabelled peptides have significant potential as radiopharmaceuticals for the diagnosis and t... more Radiolabelled peptides have significant potential as radiopharmaceuticals for the diagnosis and therapy of receptor-expressing diseases. Methods have been developed for labelling peptides with a variety of radionuclides having a broad range of chemical and physical properties. These methods include both direct (where the radionuclide is bound directly to one or more atoms of the peptide structure) and indirect techniques in which bifunctional coupling agents are employed. Although most commonly applied to date in the field of oncology, a significant number of applications in non-oncological diseases have also been proposed and these can be expected to expand as the technology progresses. An overview is presented of some peptide-receptor systems in radiopharmaceutical development and the techniques which have been employed to radiolabel these peptides with isotopes of iodine, yttrium, indium, gallium, copper and technetium. While many of the examples employed are derived from cancer ...
International journal of pharmaceutics, Jan 21, 2002
Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardia... more Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contra...
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
In nuclear medicine radiation absorbed doses are important in the patient's risk/benefit eval... more In nuclear medicine radiation absorbed doses are important in the patient's risk/benefit evaluation and are estimated by means of biological and complex mathematical models. The biological model includes radiopharmacokinetic data obtained through blood and urine samples taken at given intervals. A useful mathematical model is the MIRD model and with the value for the time of residence tau the MIRDOSE3 computer program uses several anatomic models and calculates radiation absorbed dose for 25 organs. At the Radiopharmacy Unit of the Nuclear Medicine Department at INCMNSZ two new bone seeking radiopharmaceuticals, 99mTc-ABP and 188Re-ABP, have been designed, characterized and animal-tested. Radiopharmaceutical parameters and sequential scanning were obtained for diagnostic 99mTc-ABP in 10 normal subjects and the aim was to use % 24 hour urine elimination and % bone uptake to calculate radiation absorbed dose and extrapolate the values to 188Re-ABP as the basis for a therapeutic tr...
![Research paper thumbnail of 99mTc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-receptor-positive tumors: preclinical evaluation and comparison with 111In-octreotide](https://attachments.academia-assets.com/46761162/thumbnails/1.jpg)
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2000
In this paper we describe the preclinical evaluation of 99mTc-hydrazinonicotinyl-Tyr3-octreotide ... more In this paper we describe the preclinical evaluation of 99mTc-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) using different coligands for radiolabeling and a comparison of their in vitro and in vivo properties with 111In-diethylenetriaminepentaacetic acid (DTPA)-octreotide. HYNIC-TOC was radiolabeled at high specific activities using tricine, ethylenediaminediacetic acid (EDDA), and tricine-nicotinic acid as coligand systems. Receptor binding was tested using AR42J rat pancreatic tumor cell membranes. Internalization and protein binding studies were performed, and biodistribution and tumor uptake were determined in AR42J tumor-bearing nude mice. All 99mTc-labeled HYNIC peptides showed retained somatostatin-receptor binding affinities (Kd < 2.65 nM). Protein binding and internalization rates were dependent on the coligand used. Specific tumor uptake between 5.8 and 9.6 percentage injected dose per gram (%ID/g) was found for the 99mTc-labeled peptides, compared with 4.3 %ID/g for ...
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
To compare the quality of bone scans obtained with 99mTc-ABP, a new radiopharmaceutical, and 99mT... more To compare the quality of bone scans obtained with 99mTc-ABP, a new radiopharmaceutical, and 99mTc-MDP. A comparative study within subjects was done in nine healthy volunteers, 5 female and 4 male, aged 23 to 39 years. The dose for both radiopharmaceuticals was 740 MBq; radiopharmacokinetic parameters were determined and a whole body bone scan was taken with a MultiSpect 2 gamma camera two hours post administration with a wash-out period of 72 hours between preparations. The images were independently evaluated by three nuclear medicine physicians by drawing of regions of interest (ROIs) on vertebrae, ribs, femur, sternum, joints and skull. Ratios bone/soft tissue were obtained drawing ROIs on several bones. The kappa test and the Wilcoxon rank test were used for statistical comparisons. The agreement on the quality of the images with Tc-ABP and Tc-MDP was fair (kappa 0.4). The femur/soft tissue ratio had a normal distribution and the Wilcoxon test showed no statistical difference be...
Archives of medical research, 1996
The purpose of this paper is to report the preparation of a new technetium-99m-radiopharmaceutica... more The purpose of this paper is to report the preparation of a new technetium-99m-radiopharmaceutical for bone scanning. The chelating agent for 99mTc is a new bisphosphonate, alendronate, 4-amino-1-hydroxy-butylidene-1, 1-bisphosphonate (ABP) used as a treatment for osteoporosis. ABP, because of its amino group, seems to be better suited to form a strong and stable complex with technetium-99m and therefore might be better than 99mTc-etidronate (HEDP) or 99mTc-medronate (MDP) for bone scanning. A sterile dry kit containing APB, a reducing agent and a stabilizer was prepared. The parameters studied were molar concentrations, pH, shelf life, labeling efficiency and radiochemical purity. The oven dried sterile kit was formulated with 5 mg ABP, 0.25 mg stannous fluoride and 0.025 mg gentisic acid at pH 2.5-3.5. The labeling efficiency with 20-1500 MBq of pertechnetate (99mTcO4-) was over 95% at room temperature and was stable for 5 h. Technetium-99m-alendronate was tested in two rabbits an...
188 Re radiation towards hepatocellular carcinoma (HCC) cells in mice are reported. Until now onl... more 188 Re radiation towards hepatocellular carcinoma (HCC) cells in mice are reported. Until now only 131 I-lipiodol treatment showed up to be the most effective in experiments with HCC-bearing rats, since this is the only method that leads to a prolonged improvement of the survival(2). It is predictable that Rhenium-188, owing to better physical and chemical properties, such as higher-energy
Nuclear Medicine and Biology, 2004
Nuclear Medicine and Biology, 2014
International Journal of Pharmaceutics, 2003
The aim of this work was to synthesize [166Dy]Dy/166Ho-DTPA-Biotin to evaluate its potential as a... more The aim of this work was to synthesize [166Dy]Dy/166Ho-DTPA-Biotin to evaluate its potential as a new radiopharmaceutical for targeted radiotherapy. Dysprosium-166 (166Dy) was obtained by neutron irradiation of enriched 164Dy(2)O(3) in a Triga Mark III reactor. The labeling was carried out in aqueous media at pH 8.0 by addition of [166Dy]DyCl(3) to diethylenetriaminepentaacetic-alpha,omega-bis(biocytinamide) (DTPA-Biotin). Radiochemical purity was determined by high-performance liquid chromatography (HPLC) and TLC. The biological integrity of labeled biotin was studied evaluating its avidity for avidin in an agarose column and by size-exclusion HPLC analysis of the radiolabeled DTPA-Biotin with and without the addition of avidin. Stability studies against dilution were carried out by diluting the radiocomplex solution with saline solution and with human serum at 37 degrees C for 24 h. The [166Dy]Dy/166Ho-labeled biotin was obtained with a 99.1+/-0.6% radiochemical purity. In vitro studies demonstrated that [166Dy]Dy/166Ho-DTPA-Biotin is stable after dilution in saline and in human serum and no translocation of the daughter nucleus occurs subsequent to beta(-) decay of 166Dy that could produce release of 166Ho(3+). Avidity of labeled biotin for avidin was not affected by the labeling procedure. Biodistribution studies in normal mice showed that the [166Dy]Dy/166Ho-DTPA-Biotin has a high renal clearance. In conclusion, the radiolabeled biotin prepared in this investigation has adequate properties to work as a stable in vivo generator system for targeted radiotherapy.
International Journal of Pharmaceutics, 2002
Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardia... more Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.
International Journal of Pharmaceutics, 1999
A direct labeling technique via EHDP for the preparation of 188 Re-somatostatin analogue peptide ... more A direct labeling technique via EHDP for the preparation of 188 Re-somatostatin analogue peptide b-(2-naphthyl)-D-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-amide complex was developed. The influence of reaction conditions such as pH, temperature, weak ligand concentration and stannous chloride concentration were investigated. Methods of analysis were also established permitting identification of radiochemical impurities which may be present in the radiopharmaceutical solution. Results showed that under the procedure reported herein 188 Re -peptide complex can be prepared with a radiochemical purity of 90% and a specific activity up to 1.8 GBq mg − 1 without radiolytic degradation of the product. : S 0 3 7 8 -5 1 7 3 ( 9 9 ) 0 0 0 5 4 -X
Organometallics, 2012
ABSTRACT The transmetalation reaction between zinc dithiocarbamates and rhenium carbonyls has bee... more ABSTRACT The transmetalation reaction between zinc dithiocarbamates and rhenium carbonyls has been used as a new strategy to link biomolecules to transition metals. The zinc(II) dithiocarbamate of isonipecotic acid (1) and the succinimidyl ester derivative (2) were prepared by straightforward procedures and were fully characterized by spectroscopic and X-ray diffraction methods, showing in both cases the presence of dinuclear complexes. Complex 2 reacted with all the primary and secondary amines studied (glycine methyl ester, β-alanine methyl ester, 1-(2-methoxyphenyl)piperazine, and d-(+)-glucosamine) through the activated succinimidyl ester group, linking the metallic fragment with the biomolecule by the formation of a peptidic bond and leading to the respective bioconjugated zinc complexes 3–6. In all cases, these zinc complexes could be isolated from the reaction medium by simple precipitation. These results evidence the potential of complex 2 to be used as a synthon to link the zinc dithiocarbamate fragment to biomolecules that contain an amine group. Complexes 3–6 were characterized by the usual spectroscopic methods, and all data agree with the proposed structures, which do not contain significant interactions between the zinc fragment and the functional groups of these biomolecules. The transmetalation reaction between the zinc complexes 3–6 and the rhenium carbonyl [ReBr3(CO)3]2– led to the expected rhenium dithiocarbamates 7–10 with no change in the organic dithiocarbamate fragments, confirming the viability of this reaction as a tool for linking biomolecules to transition elements. All complexes were characterized by spectroscopic methods, and the crystal structure of 8 was studied by X-ray diffraction analysis. All data demonstrated that the biomolecule is positioned far away from the fac-{Re(CO)3} fragment, and the octahedral coordination around the metal is completed by the functionalized dithiocarbamate and a phosphine ligand. Finally, analysis by ESI-MS spectrometry of the reaction between the zinc complex 4 and a water solution of [Re(H2O)3(CO)3]+ at a very low concentration (10 ppm) showed that the transmetalation reaction took place, even though the solubility of the zinc complex in water medium was as low as 0.66 ppm. This preliminary result supports the viability of this approach for the preparation of rhenium and technetium target-specific radiopharmaceuticals, since the preparations of these compounds are always performed in water medium.
Nuclear Physics B - Proceedings Supplements, 2007
Re is a beta and gamma emitter used in metabolic radiotherapy. SCINTIRAD is a multidisciplinary c... more Re is a beta and gamma emitter used in metabolic radiotherapy. SCINTIRAD is a multidisciplinary collaboration that aims at determining the radio-response of 188 Re in cells "in vitro" and the biodistribution in different organs of mice "in vivo", and studying the therapeutic effect on liver and other tumours induced in mice. Several tumour cell lines have been treated "in vitro" with a 188 Re solution. The dosimetry of 188 Re used to target the different lines of cancer cells has been evaluated using GEANT4, and preliminary results are presented. Studies to optimize the imaging of 188 Re "in vivo" have also continued, including the characterization of H8500 Flat Panel PMT and of LaBr3 crystals, and the development of dedicated electronics.
Nuclear Medicine Communications, 2002
The clinical potential of 111 In and 90 Y labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraa... more The clinical potential of 111 In and 90 Y labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated Tyr 3 -octreotide (DOTA-TOC) have been reported in a number of publications, and Phase II clinical trials of 90 Y-DOTA-TOC are currently in progress. However, to date, only a summary of the largescale preparation of these radiopharmaceuticals has been published. This publication aims to describe our experience of the small-scale synthesis of DOTA-TOC in the hope that this will assist others in the preparation of this and other similar radioconjugates. DOTA in the form of the tri-t-butyl ester was coupled to the Lys 5 (BOC) protected Tyr 3 -octreotide in N,N-dimethylformamide or N-methyl-2-pyrolidinone, in a three-step reaction involving conjugation, using O-(7-azabenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and diisopropylethyamine (DIPEA) as coupling reagents, deprotection with trifluoroacetic acid and HPLC purification of the conjugates. The product was obtained in final yields of 60+5%. The purified product was characterized by mass spectroscopy, showing a molecular weight of 1421.55+0.08. In somatostatin receptor binding assays, the unlabelled DOTA-TOC showed an effective displacement of 99m Tc labelled HYNIC-TOC (where HYNIC is hydrazinonicotinamide) (IC 50 = 0.31+0.07 nm), confirming the retention of receptor-binding affinity. The conjugate could be efficiently labelled with 111 In by addition of 111 InCl 3 and ammonium acetate buffer pH5 and heating (958C, 20 min).
Nuclear Medicine and Biology, 1997
Technetium-99m-labeled alendronate is a new radiopharmaceutical for bone scanning developed under... more Technetium-99m-labeled alendronate is a new radiopharmaceutical for bone scanning developed under strict quality control at the INNSZ. The purpose of this work was to compare the radiopharmacokinetic data and the dosimetry of 99mTc-ABP and 99mTc-MDP in 10 volunteers, after it was tested in laboratory animals. 99"Tc-ABP has shorter mean residence time (MRT) and t'lz p; is less protein bound; has a higher renal clearance; smaller Vdss, and similar bone uptake at 1 and 2 h. 99"Tc-ABP gives less radiation exposure to the patient with a 740 MBq dose, and the quality of the bone scan is excellent. 99"Tc-ABP is a better radiopharmaceutical than 99"Tc-MDP for bone scanning. Copyighr 0 19%' Elsevier Science Inc. NUCL MEL) BIOL 24;1:27-33, 1997.
Uploads
Papers by L. Melendez-Alafort