Threshold for defining PSMA-positivity prior to (177)Lu-PSMA therapy: a comparison of [(68)Ga]Ga-PSMA-11 and [(18)F]F-DCFPyL in metastatic prostate cancer

BACKGROUND: In 2022, the American Food and Drug Administration and the European Medicines Agency approved [(177)Lu]Lu-PSMA-617 (PLUVICTO™, Novartis AG, Basel, Switzerland) for radionuclide therapy with prostate-specific membrane antigen (PSMA) ligands in metastatic prostate cancer. Theranostics require appropriate patients to be identified by positron emission tomography (PET) prior to radionuclide therapy, usually employing [(68)Ga]Ga-PSMA-11. Alternatively, several (18)F-labelled PSMA-PET tracers are available and may increasingly replace (68)Ga-labelled compounds, with respect to their image quality, availability and other practical advantages. However, alternative tracers may differ in uptake behaviour, and their comparability with regard to patient selection for [(177)Lu]Lu-PSMA therapy has not yet been established. Here, we analysed whether tumour-to-background ratios determined by PET using the (18)F-labelled PSMA-specific radiopharmaceutical [(18)F]F-DCFPyL were comparable to those determined by PET using [(68)Ga]Ga-PSMA-11. RESULTS: No differences could be observed between [(68)Ga]Ga-PSMA-11-PET and [(18)F]F-DCFPyL-PET regarding tumour-to-liver ratios or tumour-to-mediastinum ratios (e. g. tumour-to-liver ratios using maximum SUV of the tumour lesion for ultra-high definition reconstructed PET images with a median of 2.5 (0.6–9.0) on [(68)Ga]Ga-PSMA-11-PET vs. 2,0 (0.6–11.4) on [(18)F]F-DCFPyL-PET). However, significant differences were observed in terms of contrast-to-noise ratios, thereby demonstrating the better image quality obtained with [(18)F]F-DCFPyL-PET. CONCLUSIONS: Our data showed that [(18)F]F-DCFPyl-PET and [(68)Ga]Ga-PSMA-11-PET provide comparable tumour-to-liver and tumour-to-mediastinum ratios. Therefore, a tumour uptake of [(18)F]F-DCFPyL above the liver background, like using [(68)Ga]Ga-PSMA-11, can be considered as equally suitable for defining PSMA-positivity by a semiquantitative assessment based on the liver background, e. g. prior to radioligand therapy with (177)Lu-labelled PSMA ligands. In addition, our data suggest a tending advantage of [(18)F]F-DCFPyL in terms of lesion detectability.