BackgroundFor individual treatment planning in patients with metastatic castration resistant prostate cancer (mCRPC), molecular analyses are increasingly used. As most patients have bone only disease, bone biopsies are often the only source for tumour tissue. However, the success rate of computed tomography (CT)-guided bone biopsies for molecular analyses in mCRPC patients is only 36.5-44%. Positron emission tomography (PET) using 68Ga-PSMA is a promising tool to increase the success rate of bone biopsies for molecular analyses in mCRPC patients. MethodsIn this multicenter study, the success rate of 68Ga-PSMA guided bone biopsies for molecular diagnostics was retrospectively evaluated in a subset of mCRPC patients who underwent a bone biopsy for whole-genome DNA sequencing within the CPCT-02 study (NCT01855477). To evaluate whether biopsies were obtained from a 68Ga-PSMA positive lesion, rigid body image registration of 68Ga-PSMA PET/CT and interventional CT was performed. This technique provided volume of interest (VOI) based quantification of 68Ga-PSMA uptake at the exact biopsy site. In addition, the potential impact of molecular analyses on clinical decision making was evaluated. ResultsSixty-nine 68Ga-PSMA-guided biopsies were eligible for primary analysis. Based on tumor percentage ≥ 30%, 70% of 68Ga-PSMA-guided biopsies was eligible for molecular analyses. At biopsy sites with positive, inconclusive or negative 68Ga-PSMA uptake, tumour percentage was ≥ 30% in 73%, 55% and 36% of the biopsies, respectively (p=0.0850). At sites of biopsies with a tumour percentage ≥ 30%, standardized uptake value (SUV)max and SUVmean of 68Ga-PSMA were significantly higher (p=0.0260 and p=0.0129 respectively), whereas Hounsfield units (HU)mean and HUmax on CT were significantly lower (p=0.0189 and p=0.0494 respectively). Molecular analyses identified potentially targetable aberrations including PTEN loss, AR amplifications, and BRCA variants. Conclusions68Ga-PSMA PET/CT is a useful technique to improve the success rate of CT-guided bone biopsies for molecular analyses in mCRPC patients. Successful bone biopsies for molecular analyses can improve individual treatment planning by detecting targetable mutations. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureR. de Wit: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy: Clovis. N. Mehra: Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi Genzyme; Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Bayer. A.A.M. Van der Veldt: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: Pierre Fabre; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (institution), Advisory / Consultancy: Ipsen. M.P. Lolkema: Research grant / Funding (institution): JNJ; Research grant / Funding (institution): Astellas. All other authors have declared no conflicts of interest.