Peripheral ganglia in healthy rats as target structures for the evaluation of PSMA imaging agents

The recent implementation of PET with prostate specific membrane antigen (PSMA)-specific radiotracers into the clinical practice has resulted in the significant improvement of accuracy in the detection of prostate carcinoma (PCa). PSMA-expression in ganglia has been regarded as an important pitfall in prostate carcinoma-PET diagnostics but has not found any practical use for diagnosis or therapy.

We explored this phenomenon and demonstrated the applicability of peripheral ganglia in healthy rats as surrogates for small PSMA positive lesions for the preclinical evaluation of diagnostic PCa PET probes. Healthy rats were measured with PET/CT using the tracers [¹⁸F]DCFPyL, [Al¹⁸F]PSMA-11 and [⁶⁸Ga]PSMA-11. Sections of ganglia were stained with an anti-PSMA antibody. [¹⁸F]DCFPyL uptake in ganglia was compared to that in LNCaP tumor xenografts in mice.

Whereas [¹⁸F]DCFPyL and [⁶⁸Ga]PSMA-11 were stable in vivo and accumulated in peripheral ganglia, [Al¹⁸F]PSMA-11 suffered from fast in vivo deflourination resulting in high bone uptake. Ganglionic PSMA expression was confirmed by immunohistochemistry. [¹⁸F]DCFPyL uptake and signal-to-noise ratio in the superior cervical ganglion was not significantly different from LNCaP xenografts.

Our results demonstrated the non-inferiority of the novel model compared to conventionally used tumor xenografts in immune compromised rodents with regard to reproducibility and stability of the PSMA signal. Furthermore, the model involves less expense and efforts while it is permanently available and avoids tumor-growth associated animal morbidity and distress. To the best of our knowledge, this is the first tumor-free model suitable for the in vivo evaluation of tumor imaging agents.