A new technique to make 68Ga-labeled pharmaceuticals widely available for clinical use

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ABSTRACT Prostate cancer is the most common malignancy in men. In approximately one third of newly diagnosed prostate cancers, the disease is indolent and does not require specific treatment. In one third of the patients the disease can be cured by surgery or radiotherapy, but the remaining third of patients recurs after initial therapy and require additional treatment. Adequate treatment of prostate cancer is hampered by a lack of imaging techniques for characterizing the aggressiveness of prostate cancer, detecting metastatic disease, and monitoring tumor response to therapy. However, one new PET imaging agent, 68Ga-PSMA-DKFZ-11 (68Ga-PSMA), has recently shown enormous promise in clinical studies to date, particularly for its exceptional accuracy in localizing recurrent and metastatic prostate cancer. Gallium-68 (68Ga) is an ideal radioisotope for molecular imaging, given its short half-life and conjugation potential with a wide array of biological molecules. However, one major obstacle for its broader clinical implementation in diseases such as prostate cancer is the lack of a widely available and cost-effective source of 68Ga. NCM USA, LLC has developed a new technique to produce several Ci of 68Ga in a medical cyclotron using a (68Zn,p,n) process. In contrast, the current technique using the 68Ge/68Ge generator can produce 50 mCi of 68Ga at most. The purpose of the collaboration of MSK and NCM is to establish if 68Ga-PSMA can be radiolabeled with cyclotron-produced 68Ga in a cost-efficient way and shipped over several hours to clinical sites, similar to the current distribution model of 18F-fluorodeoxyglucose. Challenges that must be addressed for the commercialization of cyclotron-produced 68Ga are the optimization of the 68Zn target for mass production and the potential impact of loss of specific activity during transport on tumor uptake of 68Ga-PSMA. We therefore propose a three-pronged approach in which we will (i) determine the impact of specific activity on tumor uptake of 68Ga-PSMA, (ii) design and build an optimized 68Zn target and automated 68Ga-labeling system, and (iii) conduct a clinical trial comparing cyclotron-produced 68Ga-PSMA with generator-produced 68Ga. If successful, this proposal will not only pave the way for clinical use of 68Ga-PSMA, but also for other 68Ga-labeled radiopharmaceuticals, such as receptor ligands, as well as lung and myocardial perfusion agents.