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

Abstract

Abstract Background In 2022, the American Food and Drug Administration and the European Medicines Agency approved [177Lu]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 [68Ga]Ga-PSMA-11. Alternatively, several 18F-labelled PSMA-PET tracers are available and may increasingly replace 68Ga-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 [177Lu]Lu-PSMA therapy has not yet been established. Here, we analysed whether tumour-to-background ratios determined by PET using the 18F-labelled PSMA-specific radiopharmaceutical [18F]F-DCFPyL were comparable to those determined by PET using [68Ga]Ga-PSMA-11. Results No differences could be observed between [68Ga]Ga-PSMA-11-PET and [18F]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 [68Ga]Ga-PSMA-11-PET vs. 2,0 (0.6–11.4) on [18F]F-DCFPyL-PET). However, significant differences were observed in terms of contrast-to-noise ratios, thereby demonstrating the better image quality obtained with [18F]F-DCFPyL-PET. Conclusions Our data showed that [18F]F-DCFPyl-PET and [68Ga]Ga-PSMA-11-PET provide comparable tumour-to-liver and tumour-to-mediastinum ratios. Therefore, a tumour uptake of [18F]F-DCFPyL above the liver background, like using [68Ga]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 177Lu-labelled PSMA ligands. In addition, our data suggest a tending advantage of [18F]F-DCFPyL in terms of lesion detectability.