Background: This review provides a comprehensive summary of the production of 177 Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of 177 Lu having the required quality for preparation of a variety of 177 Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of 177 Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. Methods: While both "direct" and "indirect" reactor production routes offer the possibility for sustainable 177 Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. Results: This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. Conclusion: A broad understanding and discussion of the issues associated with 177 Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of 177 Lu-labeled radiopharmaceuticals, but also help future developments.

Peptide receptor radionuclide therapy (PRRT) is a site-directed targeted therapeutic strategy that specifically uses radiolabeled peptides as biological targeting vectors designed to deliver cytotoxic levels of radiation dose to cancer cells, which overexpress specific receptors. Interest in PRRT has steadily grown because of the advantages of targeting cellular receptors in vivo with high sensitivity as well as specificity and treatment at the molecular level. Recent advances in molecular biology have not only stimulated advances in PRRT in a sustainable manner but have also pushed the field significantly forward to several unexplored possibilities. Recent decades have witnessed unprecedented endeavors for developing radiolabeled receptor-binding somatostatin analogs for the treatment of neuroendocrine tumors, which have played an important role in the evolution of PRRT and paved the way for the development of other receptor-targeting peptides. Several peptides targeting a variety of receptors have been identified, demonstrating their potential to catalyze breakthroughs in PRRT. In this review, the authors discuss several of these peptides and their analogs with regard to their applications and potential in radionuclide therapy. The advancement in the availability of combinatorial peptide libraries for peptide designing and screening provides the capability of regulating immunogenicity and chemical manipulability. Moreover, the availability of a wide range of bifunctional chelating agents opens up the scope of convenient radiolabeling. For these reasons, it would be possible to envision a future where the scope of PRRT can be tailored for patient-specific application. While PRRT lies at the interface between many disciplines, this technology is inextricably linked to the availability of the therapeutic radionuclides of required quality and activity levels and hence their production is also reviewed.

The availability of 99m Tc for single-photon imaging in diagnostic nuclear medicine is crucial, and current availability is based on the 99 Mo/ 99m Tc generator fabricated from fission-based molybdenum (F 99 Mo) produced using high enriched uranium (HEU) targets. Because of risks related to nuclear material proliferation, the use of HEU targets is being phased out and alternative strategies for production of both 99 Mo and 99m Tc are being evaluated intensely. There are evidently no plans for replacement of the limited number of reactors that have primarily provided most of the 99 Mo. The uninterrupted, dependable availability of 99m Tc is a crucial issue. For these reasons, new options being pursued include both reactor-and acceleratorbased strategies to sustain the continued availability of 99m Tc without the use of HEU. In this paper, the scientific and economic issues for transitioning from HEU to non-HEU are also discussed. In addition, the comparative advantages, disadvantages, technical challenges, present status, future prospects, security concerns, economic viability, and regulatory obstacles are reviewed. The international actions in progress toward evolving possible alternative strategies to produce 99 Mo or 99m Tc are analyzed as well. The breadth of technologies and new strategies under development to provide 99 Mo and 99m Tc reflects both the broad interest in and the importance of the pivotal role of 99m Tc in diagnostic nuclear medicine.Key Words: 99m Tc; 99 Mo production; reactor production; accelerator production; aqueous homogeneous reactor (AHR) J Nucl Med 2013; 54:313-323 DOI: 10.2967/jnumed.112.110338Obt ained from 99 Mo/ 99m Tc generators, 99m Tc is the most commonly used medical radioisotope, accounting for an estimated 30 million diagnostic procedures performed annually worldwide, with approximately 50% in the United States (1-3). Roughly twenty 99m Tc-labeled tracers are routinely used (4), and the demand for 99m Tc is estimated to increase at an annual rate of 3%-5% (5,6). A constant and reliable supply of 99m Tc is thus crucial to provide the diagnostic benefits of 99m Tc-based imaging. Reactor-produced 99 Mo (Fig. 1) has been the only source of 99m Tc, which is mainly made by irradiation of high enriched uranium (HEU) targets. Because a transition from using HEU to low enriched uranium (LEU) is being implemented to minimize potential proliferation issues (7), other 99 Mo and 99m Tc production strategies must become available. Evaluation of a variety of strategies reflects the great importance of continual availability of 99m Tc for nuclear medicine applications. Table 1 summarizes information concerning the designation of uranium with respect to fissile 235 U isotope content. Until 2011, more than 95% of the 99 Mo required for nuclear medicine applications had been primarily produced in 7 research reactors. With the exception of the new Opal Reactor in Australia, research reactors that have been major 99 Mo producers have used HEU targets (Table 2) (7,8). A few other reactors also pr...

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