Positron Emission Tomography (PET) experienced accelerated development and has become an established method for medical research and clinical routine diagnostics on patient individualized basis. Development and availability of new radiopharmaceuticals specific for particular diseases is one of the driving forces of the expansion of clinical PET. The future development of the 68Ga-radiopharmaceuticals must be put in the context of several aspects such as role of PET in nuclear medicine, unmet medical needs, identification of new biomarkers, targets and corresponding ligands, production and availability of 68Ga, automation of the radiopharmaceutical production, progress of positron emission tomography technologies and image analysis methodologies for improved quantitation accuracy, PET radiopharmaceutical regulations as well as advances in radiopharmaceutical chemistry. The review presents the prospects of the 68Ga-based radiopharmaceutical development on the basis of the current status of these aspects as well as wide range and variety of imaging agents.

Abstract:The contribution of 68 Ga to the promotion and expansion of clinical research and routine positron emission tomography (PET) for earlier better diagnostics and individualized medicine is considerable. The potential applications of 68 Ga-comprising imaging agents include targeted, pre-targeted and non-targeted imaging. This review discusses the key aspects of the production of 68 Ga and 68 Ga-based radiopharmaceuticals in the light of the impact of regulatory requirements and endpoint pre-clinical and clinical applications.

Quantitative imaging and dosimetry are crucial for individualized treatment during peptide receptor radionuclide therapy (PRRT). 177 Lu-DOTATATE and 68 Ga-DOTATOC/ 68 Ga-DOTATATE are used, respectively, for PRRT and PET examinations targeting somatostatin receptors (SSTRs) in patients affected by neuroendocrine tumors. The aim of the study was to quantitatively and qualitatively compare the performance of 68 Ga-DOTATOC and 68 Ga-DOTATATE in the context of subsequent PRRT with 177 Lu-DOTATATE under standardized conditions in the same patient as well as to investigate the sufficiency of standardized uptake value (SUV) for estimation of SSTR expression. Methods: Ten patients with metastatic neuroendocrine tumors underwent one 45-min dynamic and 3 whole-body PET/CT examinations at 1, 2, and 3 h after injection with both tracers. The number of detected lesions, SUVs in lesions and normal tissue, total functional tumor volume, and SSTR volume (functional tumor volume multiplied by mean SUV) were investigated for each time point. Net uptake rate (K i ) was calculated according to the Patlak method for 3 tumors per patient. Results: There were no significant differences in lesion count, lesion SUV, K i , functional tumor volume, or SSTR volume between 68 Ga-DOTATOC and 68 Ga-DOTATATE at any time point. The detection rate was similar, although with differences for single lesions in occasional patients. For healthy organs, marginally higher uptake of 68 Ga-DOTATATE was observed in kidneys, bone marrow, and liver at 1 h. 68 Ga-DOTATOC uptake was higher in mediastinal blood pool at the 1-h time point (P 5 0.018). The tumor-toliver ratio was marginally higher for 68 Ga-DOTATOC at the 3-h time point (P 5 0.037). Blood clearance was fast and similar for both tracers. SUV did not correlate with K i linearly and achieved saturation for a K i of greater than 0.2 mL/cm 3 /min, corresponding to an SUV of more than 25. Conclusion: 68 Ga-DOTATOC and 68 Ga-DOTATATE are suited equally well for staging and patient selection for PRRT with 177 Lu-DOTATATE. However, the slight difference in the healthy organ distribution and excretion may render 68 Ga-DOTATATE preferable. SUV did not correlate linearly with K i and thus may not reflect the SSTR density accurately at its higher values, whereas K i might be the outcome measure of choice for quantification of SSTR density and assessment of treatment outcome.