Abstract
Purpose: Ga-68 labelled PSMA is a highly sensitive agent for the diagnosis of prostate cancer. We have observed unusual gall bladder uptake of ⁶⁸Ga-DKFZ-PSMA-11 and therefore undertook this study to investigate the comparative biodistribution of Ga-68 labelled PSMA with GMP standard precursor DKFZ-PSMA-11 against that of non-GMP precursor to resolve the above observation.
Methods: Modular-Lab PharmTracer automated synthesis system was used for the routine production of ⁶⁸Ga-PSMA. Briefly, the generator was eluted with 0.1M HCl and ⁶⁸Ga was bound onto a resin and subsequently eluted in NaCl, which was then reacted with 20µg of DKFZ-PSMA-11 and 400µl of buffer and by heating at 80⁰C for 160 sec. Similarly 68Ga-labelling was performed with non-GMP PSMA precursor. The Radiochemical purity was analysed using radio-TLC and HPLC methods. All PET/CT images were acquired at 60min p.i of 150MBq of ⁶⁸Ga-PSMA synthesised using a non-GMP or GMP precursors.
Results: When non-GMP PSMA used as the precursor for preparing 68Ga-PSMA, there was significant distinct uptake of the agent by gall bladder. On the other hand, when the GMP precursor was used, there was no visible uptake of ⁶⁸Ga-PSMA by gall bladder. HPLC analysis of 68Ga-PSMA using either GMP or non-GMP precursor shows two identical peaks: peak 1 and 2 represent the thermodynamically more stable and less stable diastereomers respectively. There was significant increase in the third fraction and two smaller fractions appeared only when non-GMP precursor was used but not with the GMP standard precursor. This observation may explain the unusual uptake of the agent by gall bladder with non-GMP precursor.
Conclusion: Using GMP precursor (DKFZ-PSMA-11) for radiolabelling of ⁶⁸Ga-PSMA eliminates the unusual distinct uptake of the agent by gall bladder, which is associated with non-GMP precursor. There were no other differences in biodistribution in other organs, irrespective of the precursor used.