The Application of Unconventional PET Tracers in Nuclear Medicine

2008

Introduction: Molecular imaging (MI) is based on the selective and specific interaction of a molecular probe with a biological target which is visualized through nuclear, magnetic resonance, near infrared or other methods (1). PET (positron emitting tomography), a nuclear medical imaging modality, is ideally suited to produce three-dimensional images of various targets or processes and it enables us to obtain in vivo biological information quantitatively and noninvasively with a wide variety of PET radiopharmaceuticals. The rapidly increasing demand for highly selective probes for MI strongly pushes the development of new PET tracers and PET chemistry (1,2).

European Journal of Nuclear Medicine and Molecular Imaging, 2007

EJNMMI Radiopharmacy and Chemistry, 2016

EJNMMI Radiopharmacy and Chemistry 2016, 1(Suppl 1):OP03

American journal of nuclear medicine and molecular imaging, 2019

Targeted molecular imaging with positron emission tomography (PET) constitutes a successful technique for detecting and diagnosing disease conditions promptly and accurately, and for effectively prognosticating outcomes and treating patients with a tailored and more individualized intervention. In order to expand the success of PET in nuclear medicine, it is important to assure access to radiotracers of desired quantities and qualities. In this context, the benefit of accessing PET radiotracers through a radionuclide generator (RNG) cannot be overstated, as generators offer the potential of enriching the PET radiotracer arsenal at the medical centers both with and without onsite cyclotrons. While RNG technology to avail PET tracers is in its infancy, their use is expected to revitalize current PET practices and seems poised to broaden the palette of PET in nuclear medicine in the foreseeable future. In this review, we discuss the principles of RNGs, assess major parent/daughter pair...

Seminars in Nuclear Medicine, 2016

During past 3 decades, nuclear medicine has flourished as vibrant and independent medical specialty in Iran. Since that time, more than 200 nuclear physicians have been trained and now practicing in nearly 158 centers throughout the country. In the same period, Tc-99m generators and variety of cold kits for conventional nuclear medicine were locally produced for the first time. Local production has continued to mature in robust manner while fulfilling international standards. To meet the ever-growing demand at the national level and with international achievements in mind, work for production of other Tc-99m-based peptides such as ubiquicidin, bombesin, octreotide, and more recently a kit formulation for Tc-99m TRODAT-1 for clinical use was introduced. Other than the Tehran Research Reactor, the oldest facility active in production of medical radioisotopes, there is one commercial and three hospitalbased cyclotrons currently operational in the country. I-131 has been one of the oldest radioisotope produced in Iran and traditionally used for treatment of thyrotoxicosis and differentiated thyroid carcinoma. Since 2009, 131 I-meta-iodobenzylguanidine has been locally available for diagnostic applications. Gallium-67 citrate, thallium-201 thallous chloride, and Indium-111 in the form of DTPA and Oxine are among the early cyclotron-produced tracers available in Iran for about 2 decades. Rb-81/Kr-81m generator has been available for pulmonary ventilation studies since 1996. Experimental production of PET radiopharmaceuticals began in 1998. This work has culminated with development and optimization of the highscale production line of 18 F-FDG shortly after installation of PET/CT scanner in 2012. In the field of therapy, other than the use of old timers such as I-131 and different forms of P-32, there has been quite a significant advancement in production and application of therapeutic radiopharmaceuticals in recent years. Application of 131 I-meta-iodobenzylguanidine for treatment of neuroblastoma, pheochromocytoma, and other neuroendocrine tumors has been steadily increasing in major academic university hospitals. Also 153 Sm-EDTMP, 177 Lu-EDTMP, 90 Y-citrate, 90 Y-hydroxyapatite colloid, 188/186 Re-sulfur colloid, and 188/186 Re-HEDP have been locally developed and now routinely available for bone pain palliation and radiosynovectomy. Cu-64 has been available to the nuclear medicine community for some time. With recent reports in diagnostic and therapeutic applications of this agent especially in the field of oncology, we anticipate an expansion in production and availability. The initiation of the production line for gallium-68 generator is one of the latest exciting developments. We are proud that Iran would be joining the club of few nations with production lines for this type of generator. There are also quite a number of SPECT and PET tracers at research and preclinical stage of development preliminarily introduced for possible future clinical applications. Availability of fluorine-18 tracers and gallium-68 generators would no doubt allow rapid dissemination of PET/CT practices in various parts of our large country even far from a cyclotron facility. Also, local production and availability of therapeutic radiopharmaceuticals 340

European Journal of Nuclear Medicine and Molecular Imaging, 2008

Purpose This study was aimed at establishing a list of radionuclides of interest for nuclear medicine that can be produced in a high-intensity and high-energy cyclotron. Methods We have considered both therapeutic and positron emission tomography radionuclides that can be produced using a high-energy and a high-intensity cyclotron such as ARRONAX, which will be operating in Nantes (France) by the end of 2008. Novel radionuclides or radionuclides of current limited availability have been selected according to the following criteria: emission of positrons, low-energy beta or alpha particles, stable or short half-life daughters, half-life between 3 h and 10 days or generator-produced, favourable dosimetry, production from stable isotopes with reasonable cross sections. Results Three radionuclides appear well suited to targeted radionuclide therapy using beta ( 67 Cu, 47 Sc) or alpha ( 211 At) particles. Positron emitters allowing dosimetry studies prior to radionuclide therapy ( 64 Cu, 124 I, 44 Sc), or that can be generator-produced ( 82 Rb, 68 Ga) or providing the opportunity of a new imaging modality ( 44 Sc) are considered to have a great interest at short term whereas 86 Y, 52 Fe, 55 Co, 76 Br or 89 Zr are considered to have a potential interest at middle term. Conclusions Several radionuclides not currently used in routine nuclear medicine or not available in sufficient amount for clinical research have been selected for future production. High-energy, high-intensity cyclotrons are necessary to produce some of the selected radionuclides and make possible future clinical developments in nuclear medicine. Associated with appropriate carriers, these radionuclides will respond to a maximum of unmet clinical needs.

A. Introduction 1. The use of specific radiotracers called radiopharmaceuticals for imaging organ function and disease states is a unique capability of nuclear medicine. Unlike other imaging modalities such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Ultrasonography (US), nuclear medicine procedures are capable of mapping physiological function and metabolic activity and thereby giving more specific information about the organ function and dysfunction (1). The mapping of the radiopharmaceutical distribution in vivo provides images of functional morphology of organs in a non-invasive manner and plays an important role in the diagnosis of many common diseases associated with the malfunctioning of organs in the body as well as in the detection of certain type of cancers. The widespread utilization and growing demands for these techniques are directly attributable to the development and availability of a vast range of specific radiopharmaceuticals. B. Radioisotopes for Radiopharmaceuticals: History and Growth 2. Radiopharmaceuticals are medicinal formulations containing radioisotopes which are safe for administration in humans for diagnosis or for therapy. Although radiotracers were tried as a therapeutic medicine immediately after the discovery of radioactivity, the first significant applications came much later with the availability of cyclotrons for acceleration of particles to produce radioisotopes. Subsequently, nuclear reactors realised the ability to prepare larger quantities of radioisotopes. Radioiodine (iodine-131), for example, was first introduced in 1946 for the treatment of thyroid cancer, and remains the most efficacious method for the treatment of hyperthyroidism and thyroid cancer. 3. One of the major goals for setting up nuclear research reactors was for the preparation of radioisotopes. Among the several applications of radioisotopes, medical applications were considered to be of the highest priority. Most of the medium flux and high flux research reactors now are routinely used to produce radioisotopes for medical, and also industrial, applications. The most commonly used reactor produced isotopes in medical applications are molybdenum-99 (for production of technetium-99m), iodine-131, phosphorus-32, chromium-51, strontium-89, samarium-153, rhenium-186 and lutetium-177 (2). 4. The early use of cyclotron in radiopharmaceuticals field was for the production of long lived radioisotopes that can be used to prepare tracers for diagnostic imaging. For this, medium to high energy (20-70 MeV) cyclotrons with high beam currents were needed. Isotopes such as thallium-201, iodine-123 and indium-111 were prepared for use with single photon emission computed tomography (SPECT). With the advent of positron emission tomography (PET), there has been a surge in the production of low energy cyclotrons (9-19 MeV) exclusively for the production of short lived PET radionuclides such as fluorine-18, carbon-11, nitrogen-13 and oxygen-15. Figure 1 shows such a machine. The majority of the cyclotrons (~350) worldwide are now used for the preparation of fluorine-18 for making radiolabelled glucose for medical imaging (3).

EJNMMI Radiopharmacy and Chemistry

Background In the US, EU and elsewhere, basic clinical research studies with positron emission tomography (PET) radiotracers that are generally recognized as safe and effective (GRASE) can often be conducted under institutional approval. For example, in the United States, such research is conducted under the oversight of a Radioactive Drug Research Committee (RDRC) as long as certain requirements are met. Firstly, the research must be for basic science and cannot be intended for immediate therapeutic or diagnostic purposes, or to determine the safety and effectiveness of the PET radiotracer. Secondly, the PET radiotracer must be generally recognized as safe and effective. Specifically, the mass dose to be administered must not cause any clinically detectable pharmacological effect in humans, and the radiation dose to be administered must be the smallest dose practical to perform the study and not exceed regulatory dose limits within a 1-year period. In our experience, the main barri...

1996

2007

In this paper are presented the production methods for very "high specific activity" radionuclides (HSARNs) of vanadium (V), manganese (Mn) and thallium (Tl), which have been developed in our laboratories for labeling different chemical forms of these elements present in the echo-systems in ultra-trace amounts, for metallo-toxicological and bio-kinetic studies. Use was made of both cyclotron and thermal nuclear reactor. If the nuclear reaction and/or decay product has atomic number different from irradiated target, it is possible separating the radioactive nuclide from irradiated target, without intentional addition of isotopic carrier. These kinds of radionuclides are named No Carrier Added, NCA, and their specific activity is very high and can reach values close to the theoretical Carrier Free one, CF.