Lymphoscintigraphy in the Time of COVID-19: Effect of Molybdenum-99 Shortage on Feasibility of Sentinel Node Mapping.

Background: In the current study, we reported our experience on sentinel node mapping of breast cancer patients during the extreme shortage of Mo99-Tc99m generators using Tc-99m phytate. Methods and Results: During the period from March 7, 2019, to April 18, 2020, due to disruption of molybdenum supply chain, we used low specific activity Tc-99m pertechnetate elute (0.5-2 mCi of 99mTcO4 in 5 mL) for each kit preparation. Two or three intradermal periareolar injections were done for each patient (0.02-0.1 mCi/0.2 mL for each injection). Immediately following injection, dynamic lymphoscintigraphy was done. Surgery was done the same day of injection and the axillary sentinel node was sought using a gamma probe. Overall, 35 patients were included in the study. The specific activity of the Tc-99m elute (in 5 mL) used for kit preparation was 2 mCi/10 mg in four, 1.5 mCi/10 mg in eight, 1.25 mCi/10 mg in eight, 1 mCi/10 mg in three, 0.75 mCi/10 mg in five, and 0.5 mCi/10 mg of 99mTc-Phytate in seven patients. For the first four groups of patients, we used two 0.2 mL injections, while in the latter two groups, three 0.2 mL injections were used. At least one sentinel node was detected in all patients but three in whom axilla was involved. Conclusion: Sentinel node biopsy can be achieved with low specific activity of Tc-99m elute at the time of Mo99-Tc-99m generator shortage. If special personal protection is used, sentinel node mapping can be done in nuclear medicine departments with excellent results despite the COVID-19 pandemic and disruption of generator shipment.

Supply and Clinical Application of Actinium-225 and Bismuth-213.

The recent development of 225Ac-PSMA617 for therapy of prostate cancer has strikingly demonstrated the clinical potential of targeted alpha therapy. Further promising applications of the alpha emitters 225Actinium and its daughter nuclide 213Bismuth include the therapy of brain tumors, bladder cancer, neuroendocrine tumors, and leukemia. This paper will provide a brief overview on the current status of the clinical development of compounds labelled with 225Ac or 213Bi and describe the various production routes that are in place or are under development to meet the increasing demand for these radionuclides.

Potential Ways to Address Shortage Situations of 99Mo/99mTc.

99mTc, the most common radioisotope used in nuclear medicine, is produced in a nuclear reactor from the decay of 99Mo. There are only a few aging nuclear reactors around the world that produce 99Mo, and one of the major contributors, the National Research Universal (Canada), ceased production on October 31, 2016. The National Research Universal produced approximately 40% of the world's 99Mo supply, so with its shut down, shortages of 99Mo/99mTc are expected. Methods: Nuclear pharmacies and nuclear medicine departments throughout the United States were contacted and asked to provide their strategies for coping with a shortage of 99Mo/99mTc. Each of these strategies was evaluated on the basis of its effectiveness for conserving 99mTc while still meeting the needs of the patients. Results: From the responses, the following 6 categories of strategies, in order of importance, were compiled: contractual agreements with commercial nuclear pharmacies, alternative imaging protocols, changes in imaging schedules, software use, generator management, and reduction of ordered doses or elimination of backup doses. Conclusion: The supply chain of 99Mo/99mTc is quite fragile; therefore, being aware of the most appropriate coping strategies is crucial. It is essential to build a strong collaboration between the nuclear pharmacy and nuclear medicine department during a shortage situation. With both nuclear medicine departments and nuclear pharmacies implementing viable strategies, such as the ones proposed, the amount of 99mTc available during a shortage situation can be maximized.

Production and Clinical Applications of Radiopharmaceuticals and Medical Radioisotopes in Iran.

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 hospital-based 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 high-scale 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 are going to open exciting horizons in the field of nuclear medicine therapy. Given the available manpower, local infrastructure of SPECT imaging, and rapidly growing population, the production of Tc-99m generators and cold kit would continue to flourish in Iran.

Assessment of Using 99Mo and 99mTc Isotopes in Kuwait Medical Sector.

The Ministry of Health (MOH) in the state of Kuwait currently depends on importing the radioisotope molybdenum (Mo) in its isotopic form (Mo) to fulfill its demands. The present study was conducted on all nuclear medicine departments in the state of Kuwait. Daily, weekly, and monthly data were analyzed to statistically determine the current and future demands for the isotope Tc. This analysis was performed by collecting and analyzing data on MOH consumption of Tc for different diagnostic applications. The overall results indicate a partial decrease of 1.012% in the overall total demand for Tc up to the year 2018 for the state of Kuwait.

Feasibility studies towards future self-sufficient supply of the (99)Mo-(99m)Tc isotopes with Japanese accelerators.

In order to establish a self-sufficient supply of (99m)Tc, we studied feasibilities to produce its parent nucleus, (99)Mo, using Japanese accelerators. The daughter nucleus, (99m)Tc, is indispensable for medical diagnosis. (99)Mo has so far been imported from abroad, which is separated from fission products generated in nuclear reactors using enriched (235)U fuel. We investigated (99m)Tc production possibilities based on the following three scenarios: (1) (99)Mo production by the (n, 2n) reaction by spallation neutrons at the J-PARC injector, LINAC; (2) (99)Mo production by the (p, pn) reaction at Ep = 50-80 MeV proton at the RCNP cyclotron; (3) (99m)Tc direct production with a 20 MeV proton beam from the PET cyclotron. Among these three scenarios, scenario (1) is for a scheme on a global scale, scenario (2) works in a local area, and both cases take a long time for negotiations. Scenario (3) is attractive because we can use nearly 50 PET cyclotrons in Japan for (99m)Tc production. We here consider both the advantages and disadvantages among the three scenarios by taking account of the Japanese accelerator situation.

The medical isotope crisis: how we got here and where we are going.

(99m)Tc is the most widely used radionuclide in nuclear medicine. The reactor stoppages that occurred in recent years illustrated the vulnerability of the availability of radiotracers for imaging. With many of the reactors due for shutdown over the next 5-10 y, alternative routes to producing the (99)Mo/(99m)Tc pair are being explored. This brief review examines how we have reached this situation and what the near and distant future holds for securing the availability of these radioisotopes.

["Technetium crisis" -  causes, possible solutions and consequences for planar scintigraphy and SPECT diagnostics]. / "Techneciová krize" -  príciny, mozná resení a dopad na dia-gnostiku planární scintigrafií a SPECT.

Nuclear medicine is an important field of nuclear medicine, especially thanks to its role in in vivo imaging of important processes in human organism. An overwhelming majority of nuclear medicine examinations comprises of planar scintigraphy and single photon emission computed tomography, for decades relying on the labeling by metastable technetium nuclide (99mTc), used with a great diversity of ligands for various applications. Nuclear medicine departments utilize commercially available molybdenum technetium generators, being able to elute the nuclide at any time and prepare the radiopharmaceutical. The mother nuclide, molybdenum-99 (99Mo), is produced in just a handful of places around the world. The production places are without exception research nuclear reactors working far past their life expectancy. A concurrent temporary shutdown of two of them in the year 2009 caused a critical worldwide shortage of 99mTc. An unavoidable permanent shutdown of part of these capacities in the second decade of the 21st century will cause the second, and this time rather permanent "technetium crisis". The article focuses on history, present, potential future and possible solutions in regard to SPECT diagnostics.

Lessons from the Tc-99m shortage: implications of substituting Tl-201 for Tc-99m single-photon emission computed tomography.

BACKGROUND: In 2009, the Chalk River nuclear reactor closed for repairs that led to a critical shortage of technetium-99m (Tc-99m). Several centers used thallium-201 (Tl-201) as an alternative radiotracer for myocardial perfusion imaging. Because Tl-201 is considered by many as a suboptimal radiotracer, we sought to understand the impact of using Tl-201 (during the Tc-99m shortage) on downstream resource utilization. METHODS AND RESULTS: We performed a retrospective study at the Ottawa Heart Institute of 7402 patients (60% men; mean age, 62.6 ± 11.8 years), patients were referred for myocardial perfusion imaging between May 2008 and January 2011 (PRE_Tc-99m [2938 patients]), during (DURING_Tl-201 [2959 patients]), and after (POST_Tc-99m [1505 patients]) the Tc-99m shortage. Patients were followed for 6 months after their index myocardial perfusion imaging to determine subsequent rates of cardiac catheterization or noninvasive imaging. More downstream testing was seen in the Tl-201 cohort (639 [21.4%] patients) than the Tc-99m cohort (537 [12.1%] patients; P<0.001). After adjustment using propensity scores, differences in downstream referral rates were maintained. The downstream investigations resulted in an estimated increase in per-patient costs ($165.22; 95% confidence interval, 153.00-177.42) in the DURING_Tl-201 cohort compared with the Tc-99m cohort ($90.97; 95% confidence interval, 83.42-98.90; P<0.001). As well, the mean effective radiation dose per-patient was higher in DURING_Tl-201 (23.57 mSv; 95% confidence interval, 23.16-23.96) than in Tc-99m (12.92 mSv; 95% confidence interval, 12.55-13.40; P<0.001). CONCLUSIONS: In this single-center study, the use of Tl-201 during the Tc-99m shortage was associated with an increase in downstream testing, cost, and patient radiation exposure, but these findings may not be generalizable to other centers. Although Tl-201 provided a short-term solution to the unexpected Tc-99m shortage, long-term cost-effective solutions should be areas of future study.