For individual treatment decisions in patients with metastatic prostate cancer (mPC), molecular diagnostics are increasingly used. Bone metastases are frequently the only source for obtaining metastatic tumor tissue. However, the success rate of computed tomography (CT)-guided bone biopsies for molecular analyses in mPC patients is only ~40%. Positron emission tomography (PET) using Gallium-68 prostate specific membrane antigen (68Ga-PSMA) is a promising tool to improve the harvest rate of bone biopsies for molecular analyses. Aim of this study was to determine the success rate of 68Ga-PSMA guided bone biopsies for molecular diagnostics in mPC patients. Methods: Within a prospective multicenter whole-genome sequencing trial (NCT01855477), 69 mPC patients underwent 68Ga-PSMA PET/CT prior to bone biopsy. Primary endpoint was success rate (tumor percentage ≥30%) of 68Ga-PSMA guided bone biopsies. At biopsy sites, 68Ga-PSMA uptake was quantified using rigid body image registration of 68Ga-PSMA PET/CT and interventional CT. Actionable somatic alterations were identified. Results: Success rate of 68Ga-PSMA guided biopsies for molecular analyses was 70%. At biopsy sites categorized as positive, inconclusive, or negative for 68Ga-PSMA uptake, 70%, 64%, and 36% of biopsies were tumor positive (≥30%), respectively (p=0.0610). In tumor positive biopsies, 68Ga-PSMA uptake was significantly higher (p=0.008), whereas radiodensity was significantly lower (p=0.006). With an area under the curve of 0.84 and 0.70, both 68Ga-PSMA uptake (maximum standardized uptake value) and radiodensity (mean Hounsfield Units) were strong predictors for a positive biopsy. Actionable somatic alterations were detected in 73% of the sequenced biopsies. Conclusion: In patients with mPC, 68Ga-PSMA PET/CT improves the success rate of CT-guided bone biopsies for Downloaded from jnm.snmjournals.org by on November 26, 2020. For personal use only. 4 molecular analyses, thereby identifying actionable somatic alterations in more patients. Therefore, 68Ga-PSMA PET/CT may be considered for guidance of bone biopsies in both clinical practice and clinical trials.

bone biopsy, 68Ga-PSMA-PET, molecular diagnostics, whole genome sequencing, prostate cancer.
dx.doi.org/10.2967/jnumed.119.241109, hdl.handle.net/1765/131610
The Journal of Nuclear Medicine
Department of Medical Oncology

de Jong, A.C., Smits, M, van Riet, J., Fütterer, J, Brabander, T., Hamberg, A.P, … van der Veldt, A.A.M. (2020). Ga-68-PSMA-Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer. The Journal of Nuclear Medicine, 61(11), 1607–1614. doi:10.2967/jnumed.119.241109