Assessment of Simplified Methods for Quantification of F-18-FDHT Uptake in Patients with Metastatic Castration-Resistant Prostate Cancer

OBJECTIVES: 18F‐fluorodihydrotestosterone (18F‐FDHT) PET/CT potentially provides a non‐invasive method for assessment of androgen receptor expression in patients with metastatic castration‐resistant prostate cancer (mCRPC). The objective of this study was to assess simplified methods for quantifying 18F‐FDHT uptake in mCRPC patients and to assess effects of tumour perfusion on these 18F‐FDHT uptake metrics. METHODS: Seventeen mCRPC patients were included in this prospective observational multicentre study. Test and retest 30 minute dynamic 18F‐FDHT PET/CT scans with venous blood sampling were performed in 14 patients. In addition, arterial blood sampling and dynamic 15O‐H2O scans were obtained in a subset of six patients. Several simplified methods were assessed: Patlak plots, standardized uptake values normalized to bodyweight (SUVBW) or lean body mass (SUVLBM), SUV normalized to whole blood (SUVWB) or parent plasma activity concentration (SUVPP), SUV normalized to the area under the parent plasma (SUVAUC,PP) or whole blood input curve (SUVAUC,WB), and SUVBW corrected for sex hormone‐binding globulin (SHBG) levels (SUVSHBG). Results were correlated with parameters derived from full pharmacokinetic 18F‐FDHT and 15O‐H2O. Finally, repeatability of individual quantitative uptake metrics was assessed. RESULTS: Eighty seven 18F‐FDHT avid lesions were evaluated. 18F‐FDHT uptake was best described by an irreversible 2‐tissue compartment model. Replacing the continuous metabolite corrected arterial plasma input function with an image derived input function (IDIF) in combination with venous sample data provided similar Ki results (R2 =0.98). Patlak Ki and SUVAUC,PP showed excellent correlation (R2 >0.9). SUVBW showed a moderate correlation to Ki (R2 =0.70, presumably due to fast FDHT metabolism. When calculating SUVSHBG, Downloaded from jnm.snmjournals.org by on December 5, 2019. For personal use only. 2 correlation to Ki improved (R2 =0.88). Repeatability of full kinetic modelling parameters was inferior to that of simplified methods (repeatability coefficients >36% vs. <28%, respectively). 18F‐FDHT uptake showed minimal blood flow dependency. CONCLUSION: 18F‐FDHT kinetics in mCRPC patients are best described by an irreversible 2‐tissue compartment model with blood volume parameter. SUVAUC,PP showed a near perfect correlation with the irreversible 2‐tissue compartment model analysis and can be used for accurate quantification of 18F‐FDHT uptake in whole‐ body PET/CT scans. In addition, SUVSHBG could potentially be used as an even simpler method to quantify 18F‐FDHT uptake when less complex scanning protocols and accuracy are required.

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