Immuno-PET in Pontine Glioma: More Than Meets the Eye?

Abstract

610 Objectives: The success of PET imaging with 68Ga-labeled somatostatin and PSMA ligands has created a markedly increased demand for 68Ga that is challenging to meet with existing 68Ge/68Ga generators. In addition, preparation of patient doses is relatively expensive, because only small batches of the ligands can be prepared that each need to undergo QC procedures. The objective of this study was therefore to investigate the cyclotron production of 68Ga from a solid 68Zn target and the feasibility of using cyclotron produced 68Ga for preparing 68Ga-PSMA-11. We also evaluated how a decrease of specific activity - as would occur during the shipment of larger batches of 68Ga-PSMA-11 - affects tumor and normal organ uptake of [asterisk]Ga-PSMA-11 in mouse models of prostate cancer. Methods: Enriched 68Zn foils were irradiated were irradiated with 11.5 MeV protons for 1-3 h at a beam current of 30-75 µA in a GET PETTRACE cyclotron. The irradiated foils were dissolved in 10 N HCl and the solution passed through a cation exchanging resin to trap 68Ga and 68Zn. 68Zn was then eluted from the column using HBr in 80% acetone. Finally, 68Ga was eluted with 3 N HCl and used to label 68Ga-PSMA-11. In order to study the impact of injected mass on tumor and normal organ of [asterisk]Ga-PSMA-11 we injected mice bearing PSMA expressing PC3-PIP or LNCaP tumors with 3.3 - 10000 pmol of total ligand (67Ga-PSMA-11 and PSMA-11) labeled with 100-200 µCi of (67Ga) and performed a biodistribution study 1 h post injection. We also injected tumor bearing with cyclotron produced and generator produced 68Ga-PSMA-11 and performed PET imaging studies 1h post injection. Results: Up to 4.2 Ci of 68Ga were produced from the 68Zn foil before purification and, 1.8 Ci after purification. The 67Ga content was less than 0.1%. Specific activity of the produced 68Ga-PSMA-11 was 2.2-7.0 mCi/µg and radiochemical purity > 99%. The 68Ga-PSMA-11 met all the usual criteria for PET radiopharmaceuticals (bubble, LAL, and sterility test). There was no significant change in tumor uptake of 67Ga-PSMA-11 up to an injected mass of 1000 pmol for PC3-PIP and LNCaP tumors (333-fold range). PET images of tumor bearing mice injected with 800 pmol of 68Ga-PSMA11 demonstrated identical biodistribution in normal organs and tumors. Conclusions: 68Ga can be produced in Ci amounts using a medical cyclotron. The cyclotron produced 68Ga product appears suitable for labeling PSMA11 for future clinical trials.The injected mass of PSMA-11 (on a per weight basis) had no significant impact on tumor uptake in mice up to a more than 300-fold higher mass than used for human PET/CT studies with 68Ga-PSMA11. This suggests that batches of cyclotron produced 68Ga-PSMA11 may be shipped for several hours after production.