Current Radiopharmaceuticals - Volume 12, Issue 3, 2019

Objective: Myocardial Perfusion Imaging (MPI) with radiotracers is an integral component in evaluation of the patients with known or suspected coronary artery diseases (CAD). 99mTc-Sestamibi and 99mTc-Tetrofosmin are commercial radiopharmaceuticals for MPI by single photon-emission computed tomography (SPECT). Despite their widespread clinical applications, they do not meet the requirements of an ideal perfusion imaging agent due to their inability to linearly track the regional myocardial blood flow rate at >2.5 mL/min/g. With tremendous development of CZT-based SPECT cameras over the past several years, the nuclear cardiology community has been calling for better perfusion radiotracers with improved extraction and biodistribution properties. Methods: This review will summarize recent research efforts on new cationic and neutral 99mTc radiotracers for SPECT MPI. The goal of these efforts is to develop a 99mTc radiotracer that can be used to detect perfusion defects at rest or under stress, determine the regional myocardial blood flow, and measure the perfusion and left ventricular function. Results: The advantage of cationic radiotracers (e.g. 99mTc-Sestamibi) is their long myocardial retention because of the positive molecular charge and fast liver clearance kinetics. 99mTc-Teboroxime derivatives have a high initial heart uptake (high first-pass extraction fraction) due to their neutrality. 99mTc- 3SPboroxime is the most promising radiotracer for future clinical translation considering its initial heart uptake, myocardial retention time, liver clearance kinetics, heart/liver ratios and SPECT image quality. Conclusion: 99mTc-3SPboroximine is an excellent example of perfusion radiotracers, the heart uptake of which is largely relies on the regional blood flow. It is possible to use 99mTc-3SPboroximine for detection of perfusion defect(s), accurate quantification and determination of regional blood flow rate. Development of such a 99mTc radiotracer is of great clinical benefit for accurate diagnosis of CAD and assessing the risk of future hard events (e.g. heart attack and sudden death) in cardiac patients.

Background: A significant number of developing countries have no facilities to produce medical radioisotopes and radiopharmaceuticals. Objective: In this paper we show that access to life-saving radioisotopes and radiopharmaceuticals and the geographical distribution of corresponding infrastructure is highly unbalanced worldwide. Methods: We discuss the main issues which need to be addressed in order to establish the production of radioisotopes and radiopharmaceuticals, which are especially important for developing countries as newcomers in the field. The data was gathered from several sources, including databases maintained by the International Atomic Energy Agency (IAEA), World Health Organization (WHO), and other international organizations; personal interactions with representatives in the nuclear medicine field from different regions of the world; and relevant literature. Results: Developing radioisotope and radiopharmaceutical production program and installing corresponding infrastructure requires significant investments, both man-power and financial. Support already exists to help developing countries establish their medical radioisotope production installations from several organizations, such as IAEA. Conclusion: This work clearly shows that access to life-saving radioisotopes and the geographical distribution of corresponding infrastructure is highly unbalanced. Technology transfer is important as it not only immediately benefits patients, but also provides employment, economic activity and general prosperity in the region to where the technology transfer is implemented.

In recent years, PET using radiolabelled amino acids has gained considerable interest as an additional tool besides MRI to improve the diagnosis of cerebral gliomas and brain metastases. A very successful tracer in this field is O-(2-[18F]fluoroethyl)-L-tyrosine (FET) which in recent years has replaced short-lived tracers such as [11C]-methyl-L-methionine in many neuro-oncological centers in Western Europe. FET can be produced with high efficiency and distributed in a satellite concept like 2- [18F]fluoro-2-deoxy-D-glucose. Many clinical studies have demonstrated that FET PET provides important diagnostic information regarding the delineation of cerebral gliomas for therapy planning, an improved differentiation of tumor recurrence from treatment-related changes and sensitive treatment monitoring. In parallel, a considerable number of experimental studies have investigated the uptake mechanisms of FET on the cellular level and the behavior of the tracer in various benign lesions in order to clarify the specificity of FET uptake for tumor tissue. Further studies have explored the effects of treatment related tissue alterations on tracer uptake such as surgery, radiation and drug therapy. Finally, the role of blood-brain barrier integrity for FET uptake which presents an important aspect for PET tracers targeting neoplastic lesions in the brain has been investigated in several studies. Based on a literature research regarding experimental FET studies and corresponding clinical applications this article summarizes the knowledge on the uptake behavior of FET, which has been collected in more than 30 experimental studies during the last two decades and discusses the role of these results in the clinical context.

Background: Nephrotoxicity is a prevalent consequence of cancer treatment using radiotherapy and chemotherapy or their combination. There are two methods; histological and biochemical, to assess the kidney damage caused by toxic agents in animal studies. Although these methods are used for the try-out of renoprotective factors, these methods are invasive and time-consuming, and also, lack the necessary sensitivity for primary diagnosis. Quantitative renal 99mTc-DMSA scintigraphy is a noninvasive, precise and sensitive radionuclide technique which is used to assess the extent of kidney damage, so that the extent of injury to the kidney will be indicated by the renal uptake rate of 99mTc-DMSA in the kidney. In addition, this scintigraphy evaluates the effect of the toxic agents by quantifying the alterations in the biodistribution of the radiopharmaceutical. Conclusion: In this review, the recent findings about the renoprotective agents were evaluated and screened with respect to the use of 99mTc-DMSA , which is preclinically and clinically used for animal cases and cancer patients under the treatment by radiotherapy and chemotherapy.

Purposes: The aims of the present study were to: 1- critically assess the utility of L-3,4- dihydroxy-6-18Ffluoro-phenyl-alanine (18F-DOPA) and O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) Positron Emission Tomography (PET)/Computed Tomography (CT) in patients with high grade glioma (HGG) and 2- describe the results of 18F-DOPA and 18F-FET PET/CT in a case series of patients with recurrent HGG. Methods: We searched for studies using the following databases: PubMed, Web of Science and Scopus. The search terms were: glioma OR brain neoplasm and DOPA OR DOPA PET OR DOPA PET/CT and FET OR FET PET OR FET PET/CT. From a mono-institutional database, we retrospectively analyzed the 18F-DOPA and 18F-FET PET/CT of 29 patients (age: 56 ± 12 years) with suspicious for recurrent HGG. All patients underwent 18F-DOPA or 18F-FET PET/CT for a multidisciplinary decision. The final definition of recurrence was made by magnetic resonance imaging (MRI) and/or multidisciplinary decision, mainly based on the clinical data. Results: Fifty-one articles were found, of which 49 were discarded, therefore 2 studies were finally selected. In both the studies, 18F-DOPA and 18F-FET as exchangeable in clinical practice particularly for HGG patients. From our institutional experience, in 29 patients, we found that sensitivity, specificity and accuracy of 18F-DOPA PET/CT in HGG were 100% (95% confidence interval- 95%CI - 81-100%), 63% (95%CI: 39-82%) and 62% (95%CI: 39-81%), respectively. 18F-FET PET/CT was true positive in 4 and true negative in 4 patients. Sensitivity, specificity and accuracy for 18F-FET PET/CT in HGG were 100%. Conclusion: 18F-DOPA and 18F-FET PET/CT have a similar diagnostic accuracy in patients with recurrent HGG. However, 18F-DOPA PET/CT could be affected by inflammation conditions (false positive) that can alter the final results. Large comparative trials are warranted in order to better understand the utility of 18F-DOPA or 18F-FET PET/CT in patients with HGG.

Objectives: Recent gallium-68 labeled peptides are of increasing interest in PET imaging in nuclear medicine. Somakit TOC® is a radiopharmaceutical kit registered in the European Union for the preparation of [68Ga]Ga-DOTA-TOC used for the diagnosis of neuroendocrine tumors. Development of a labeling process using a synthesizer is particularly interesting for the quality and reproducibility of the final product although only manual processes are described in the Summary of Product (SmPC) of the registered product. The aim of the present study was therefore to evaluate the feasibility and value of using an automated synthesizer for the preparation of [68Ga]Ga-DOTA-TOC according to the SmPC of the Somakit TOC®. Methods: Three methods of preparation were compared; each followed the SmPC of the Somakit TOC®. Over time, overheads, and overexposure were evaluated for each method. Results: Mean±SD preparation time was 26.2±0.3 minutes for the manual method, 28±0.5 minutes for the semi-automated, and 40.3±0.2 minutes for the automated method. Overcost of the semi-automated method is 0.25€ per preparation for consumables and from 0.58€ to 0.92€ for personnel costs according to the operator (respectively, technician or pharmacist). For the automated method, overcost is 70€ for consumables and from 4.06€ to 6.44€ for personnel. For the manual method, extremity exposure was 0.425mSv for the right finger, and 0.350mSv for the left finger; for both the semi-automated and automated method extremity exposure were below the limit of quantification. Conclusion: The present study reports for the first time both the feasibility of using a [68Ga]- radiopharmaceutical kit with a synthesizer and the limits for the development of a fully automated process.

Background: 68Ga-PSMA is a widely useful PET/CT tracer for prostate cancer imaging. Being a transmembrane protein acting as a glutamate carboxypeptidase enzyme, PSMA is highly expressed in prostate cancer cells. PSMA can also be labeled with 64Cu, offering a longer half-life and different resolution imaging. Several studies documented bio-distribution and pitfalls of 68Ga-PSMA as well as of 64Cu- PSMA. No data are reported on differences between these two variants of PSMA. Our aim was to evaluate physiological distribution of these two tracers and to analyze false positive cases. Methods: We examined tracer bio-distribution in prostate cancer patients with negative 68Ga-PSMA PET/CT (n=20) and negative 64Ga-PSMA PET/CT (n=10). A diagnostic pitfall for each tracer was documented. Result: Bio-distribution of both tracers was similar, with some differences due to renal excretion of 68Ga- PSMA and biliary excretion of 64Cu-PSMA. 68Ga-PSMA uptake was observed in sarcoidosis while 64Cu- PSMA uptake was recorded in pneumonitis. Discussion: Both tracers may present similar bio-distribution in the human body, with similar uptake in exocrine glands and high intestinal uptake. Similarly to other tracers, false positive cases cannot be excluded in clinical practice. Conclusion: The knowledge of difference in bio-distribution between two tracers may help in interpretation of PET data. Diagnostic pitfalls can be documented, due to the possibility of PSMA uptake in inflammation. Our results are preliminary to future studies comparing diagnostic accuracies of 68Ga-PSMA and 64Cu-PSMA.

Background: Radiotherapy (RT) is a treatment method for cancer using ionizing radiation (IR). The interaction between IR with tissues produces free radicals that cause biological damages.As the largest organ in the human body, the skeletal muscles may be affected by detrimental effects of ionizing radiation. To eliminate these side effects, we used melatonin, a major product secreted by the pineal gland in mammals, as a radioprotective agent. Materials and Methods: For this study, a total of sixty male Wistar rats were used. They were allotted to 4 groups: control (C), melatonin (M), radiation (R) and melatonin + radiation (MR). Rats’ right hind legs were irradiated with 30 Gy single dose of gamma radiation, while 100 mg/kg of melatonin was given to them 30 minutes before irradiation and 5 mg/ kg once daily afternoon for 30 days. Five rats in each group were sacrificed 4, 12 and 20 weeks after irradiation for histological and biochemical examinations. Results: Our results showed radiation-induced biochemical, histological and electrophysiological changes in normal rats’ gastrocnemius muscle tissues. Biochemical analysis showed that malondialdehyde (MDA) levels significantly elevated in R group (P<0.001) and reduced significantly in M and MR groups after 4, 12, and 20 weeks (P<0.001), However, the activity of catalase (CAT) and superoxide dismutase(SOD)decreased in the R group and increased in M and MR groups for the same periods of time compared with the C group (P<0.001), while melatonin administration inverted these effects( P<0.001).Histopathological examination showed significant differences between R group for different parameters compared with other groups (P<0.001). However, the administration of melatonin prevented these effects(P<0.001). Electromyography (EMG) examination showed that the compound action potential (CMAP) value in the R group was significantly reduced compared to the effects in the C and M groups after 12 and 20 weeks (P<0.001). The administration of melatonin also reversed these effects (P<0.001). Conclusion: Melatonin can improve biochemical, electrophysiological and morphological features of irradiated gastrocnemius muscle tissues.Our recommendation is that melatonin should be administered in optimal dose. For effective protection of muscle tissues, and increased therapeutic ratio of radiation therapy, this should be done within a long period of time.