A cost effective method for the preparation of sodium fluoride [18F]NaF for PET-CT imaging by using an in-house designed module.

We report the development of a manual module for the preparation of [18F]NaF for metastatic bone cancer imaging. By using this simple module, [18F]NaF production can be carried out inexpensively without using commercially available kits. The module can be used for making [18F]NaF from freshly irradiated H218O water or with left over activity in the target after [18F]FDG production. The product meets all quality control parameters.

Preparation of Patient Doses of [177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA-617 with Carrier Added (CA) and No Carrier Added (NCA) 177Lu.

Purpose: [177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA-617 used for targeted radionuclide therapy are very often prepared in the hospital radiopharmacy. The preparation parameters vary depending upon the specific activity of the 177Lu used. The aim of this study was to develop optimized protocols to be used in the nuclear medicine department for the preparation of patient doses of the above radiopharmaceuticals. Method: 177Lu (CA and NCA) were used for radiolabeling DOTATATE and PSMA-617. Parameters studied are 177Lu of different specific activity and different peptide concentrations and two different buffer systems. Paper and thin layer chromatography systems were used for estimating the radiochemical yield as well as radiochemical purity. Solid-phase extraction was used for the purification of the labeled tracers. Results: [177Lu]Lu-DOTATATE was prepared with CA 177Lu (n = 13) and NCA177Lu (n = 6). Four batches each of [177Lu]Lu-PSMA-617 were prepared using CA and NCA 177Lu. Radiochemical yields > 80% and final product with less than < 1% radiochemical impurity could be obtained in all batches which were used for therapy. Conclusion: Robust protocols for the preparation of clinical doses of [177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA-617 were developed and used for the preparation of clinical doses. The quality of the SPECT images of both the tracers are consistent with the expected uptake in respective diseases.

Experience of 6-l-[18F]FDOPA Production Using Commercial Disposable Cassettes and an Automated Module.

Purpose: The clinical demand of 6-l-[ 18F] FDOPA is gaining rapidly for imaging neurodegenerative diseases by using positron emission tomography. Hence, large-scale production of 6-l-[18F] FDOPA is necessary. This paper describes our experience on the production of 6-l-[18F]FDOPA via nucleophilic synthesis using NEPTIS module and a commercially available cassette based chemistry. Method: 6-l-[18F]FDOPA production could be completed in three synthetic steps by using ABX nitro precursor. The precursor is first labeled with18F by replacing a -NO2 leaving group followed by purification using a solid phase cartridge. In the subsequent step, the radiolabeled precursor is oxidized using meta chloroperoxy benzoic acid hydrolyzed to remove the four different protecting groups. The product is finally purified in a series of solid phase cartridges to yield radiochemically pure 6-l-[18F]FDOPA. Results: Total 36 batches of 6-l-[18F]FDOPA were produced. The decay uncorrected yield were 5.5 ± 1.5% (n = 33) which corresponds to a decay corrected yield of 11.8 ± 3.2% (n = 33). The radiochemical purity of the product obtained is always > 95%. Conclusion: The yields obtained are low and hence there is a need to improve synthetic chemistry. In order to understand the efficiency of each step, a detailed analysis using the radioactive traces obtained from the automated module was carried out. The radiolabeling yield of precursor is only about 50% and there is subsequent reduction in activity in the oxidation as well as hydrolysis steps. Despite the low radiochemical yields, the product obtained was suitable for imaging.

Utility of 68Ga-PSMA-11 PET/CT in Imaging of Glioma-A Pilot Study.

BACKGROUND: Imaging of gliomas remains challenging. The aim of the study was to assess the feasibility of using Ga-PSMA-11 PET/CT for imaging gliomas. METHODS: Fifteen patients with glioma from 2 centers were included in the study. Ten patients were treated cases of glioblastoma with suspected recurrence. Two patients were sent for assessing the nature (primary lesion/metastasis) of space-occupying lesion in the brain; 3 patients were imaged immediately after surgery and before radiotherapy. Target-to-background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background. RESULTS: Among the 10 cases with suspected recurrence, scan was positive in 9, subsequent surgery was done, and histopathology proved it to be true recurrence. In the scan-negative case on follow-up, no evidence of disease could be made clinically or radiologically. Among the other cases the presence or absence of disease could be unequivocally identified on the Ga-PSMA-11 brain scan and correlated with the histopathology or other imaging. Apart from the visual assessment quantitative assessment of the lesions with TBR also showed a significantly high TBR value for those with true disease compared with those with no disease. CONCLUSIONS: In the evaluation of gliomas, Ga-PSMA-11 PET/CT brain imaging is a potentially useful imaging tool. The use of Ga-PSMA-11 brain PET/CT in evaluation of recurrent glioma seems promising. Absence of physiological uptake of Ga-PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of glioma lesions.

Radiolabeled enzyme inhibitors and binding agents targeting PSMA: Effective theranostic tools for imaging and therapy of prostate cancer.

Because of the broad incidence, morbidity and mortality associated with prostate-derived cancer, the development of more effective new technologies continues to be an important goal for the accurate detection and treatment of localized prostate cancer, lymphatic involvement and metastases. Prostate-specific membrane antigen (PSMA; Glycoprotein II) is expressed in high levels on prostate-derived cells and is an important target for visualization and treatment of prostate cancer. Radiolabeled peptide targeting technologies have rapidly evolved over the last decade and have focused on the successful development of radiolabeled small molecules that act as inhibitors to the binding of the N-acetyl-l-aspartyl-l-glutamate (NAAG) substrate to the PSMA molecule. A number of radiolabeled PSMA inhibitors have been described in the literature and labeled with SPECT, PET and therapeutic radionuclides. Clinical studies with these agents have demonstrated the improved potential of PSMA-targeted PET imaging agents to detect metastatic prostate cancer in comparison with conventional imaging technologies. Although many of these agents have been evaluated in humans, by far the most extensive clinical literature has described use of the 68Ga and 177Lu agents. This review describes the design and development of these agents, with a focus on the broad clinical introduction of PSMA targeting motifs labeled with 68Ga for PET-CT imaging and 177Lu for therapy. In particular, because of availability from the long-lived 68Ge (T1/2=270days)/68Ga (T1/2=68min) generator system and increasing availability of PET-CT, the 68Ga-labeled PSMA targeted agent is receiving widespread interest and is one of the fastest growing radiopharmaceuticals for PET-CT imaging.

Production of (177)Lu for Targeted Radionuclide Therapy: Available Options.

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: an overview.

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.

Sustained availability of 99mTc: possible paths forward.

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 accelerator-based 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.