Abstract 3671: Phenotypic heterogeneity within prostate cancer bone metastases measured by 18F-DCFBC PET/CT and 18F-NaF PET/CT
Authors: Harmon Stephanie A. , Mena Esther , Shih Joanna , Bergvall Ethan , Adler Stephen , Mehralivand Sherif , Madan Ravi A. , Gulley James L. , Dahut William L. , Turkbey Baris , Choyke Peter L. , Lindenberg M Liza 
Published: August 2018

Abstract
Purpose: The purpose of this study was to compare the spatial colocalization of prostate-specific membrane antigen (PSMA) targeting agent 18F-DCFBC PET/CT, a marker which demonstrates correlation with tumor aggressiveness, and 18F-NaF PET/CT, a marker of osteoblastic activity, within bone lesions of patients with metastatic prostate cancer. Methods: Twenty-eight metastatic prostate cancer patients received 18F-DCFBC PET/CT and 18F-NaF PET/CT scans (median interval 7 days, range 1-57). Tracer-specific regions of interest (ROI) were derived from threshold containing 80% of maximum SUV (SUV80%). Lesion detection and uptake was compared across the two PET/CT agents using non-parametric testing (Spearman correlation, Wilcoxon rank sum) accounting for intra-patient correlation. Lesion-specific registration was completed by global alignment of skeletal segments followed by local neighborhood optimization of area surrounding lesion. Spatial concordance was evaluated using overlap volume (OV), calculated as the volume of ROI intersection (shared volume) relative to the minimum volume of NaF-ROI or PSMA-ROI to account for differences in ROI volumes. Differences in uptake and CT Hounsfield units (HU) were compared within concordant (overlapping) and discordant (NaF-only, PSMA-only) regions of the same lesion using Wilcoxon signed rank test accounting for intra-patient correlation. Results: Twenty-six patients had positive NaF or DCFBC PET/CT scans, with a total of 241 metastatic sites identified. Lesion-level NaF SUV80% and DCFBC-2hr SUV80% were not significantly correlated at baseline (ρ=0.41, p&gt;0.1). Lesion-level NaF-SUV80% was lower in bone lesions detected only by NaF (N=96) compared to NaF-SUV80% in bone lesions detected by both tracers (N=82), nearing significance (p=0.065). This pattern was not observed in DCFBC-SUV80% (p=0.5). To avoid bias from motion artifacts, only lesions in pelvis and spine were considered for voxel-based analysis (N=42). NaF and PSMA ROIs showing varying levels of spatial concordance (OV mean=0.26, range=0-1), which was modestly associated with higher sclerosis (ρ=0.4, p=0.01) and weakly associated with lower PSMA activity (ρ=0.3, p=0.07). Intra-lesion PSMA-only regions were significantly less sclerotic compared to concordant (p=0.04) and NaF-only (p=0.03) regions, indicating regions of active tumor seeding extend beyond regions of active bone remodeling within the tumor. Conclusions: Metastatic seeding and growth of prostate cancer in bone is biologically complex and dependent on bone microenvironment. We find regions of aggressive cellular activity (PSMA-targeting PET/CT) show heterogeneous colocalization with regions of rapid bone remodeling (NaF PET/CT) within sites of metastatic bone disease. These preliminary findings are important for consideration of targeted radionuclide therapies in metastatic prostate cancer.
Citation Format: Stephanie A. Harmon, Esther Mena, Joanna Shih, Ethan Bergvall, Stephen Adler, Sherif Mehralivand, Ravi A. Madan, James L. Gulley, William L. Dahut, Baris Turkbey, Peter L. Choyke, M Liza Lindenberg. Phenotypic heterogeneity within prostate cancer bone metastases measured by 18F-DCFBC PET/CT and 18F-NaF PET/CT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3671.