Report on the PET/CT image-based radiation dosimetry of 18FDHT in women, an imaging agent with new applications for evaluation of androgen receptor status in patients with metastatic breast cancer.

1630 Objectives: 18F-Fluorodihydrotestosterone (18FDHT), the radiolabeled analog of the androgen dihydrotestosterone, has been used in clinical trials to assess androgen receptor (AR) expression in castration-resistant prostate cancer in men and in metastatic AR+ breast cancer in women. Human studies of 18FDHT radiation dosimetry in male prostate cancer patients have been published; however, to our knowledge, there have been no published studies in women. This work presents the first report of 18FDHT biodistribution and radiation dosimetry in female patients. Methods: In a prospective clinical trial (G200802, GTx, Inc, NCT02463032), 18FDHT radiation dosimetry was performed in a cohort of 11 female patients at baseline (S0) prior to therapy and at two additional time points (S1 and S2) during therapy for ER+/AR+ metastatic breast cancer. PET/CT images were acquired from the mid-thighs through the vertex of the skull starting at 52 ± 6 min after intravenous administration of 8.4 ± 0.8 mCi [310 ± 29 MBq] of 18FDHT. 18FDHT activity (SUVorgan) was measured for whole body, aorta blood pool, contralateral breast, lungs, spleen, liver, gallbladder, kidneys, and urinary bladder, and fit to monoexponential functions to derive the residence times in source organs. Radiation dosimetry was performed in OLINDA/EXM software application. Biological clearance times were calculated with the MIRD dynamic urinary bladder model and the ICRP 30 gastrointestinal (GI) tract model, and equivalent dose to target organs and effective dose to the whole body were calculated with the MIRD internal dosimetry method. Results: PET/CT images showed that 18FDHT activity in the blood pool was higher than surrounding muscle at 1-hour post administration, and that organ uptake was highest within the liver, spleen, kidneys, gallbladder and urinary bladder, which was consistent with biological clearance through urinary and hepatobiliary excretion. Statistical analysis found no significant changes in SUVorgan measured at baseline versus on therapy for the whole body and for most of the source organs except the liver. The liver showed a small but statistically significant decrease in SUVorgan at the S1 and S2 time points (p < 0.01) and a resultant decrease in the radiation dose to the GI track. At S0 baseline, radiation dosimetry of 18FDHT in female patients showed an effective dose to the whole body of 0.020 ± 0.001 mSv/MBq (mean ± standard deviation), and the urinary bladder was the critical organ with an average equivalent dose of 0.061 ± 0.024 mSv/MBq. At S1 and S2 while the patients were on therapy for ER+/AR+ breast cancer, there were no changes in the effective dose to the whole body and the equivalent dose to the critical organ of the urinary bladder versus the doses at S0 baseline. Conclusions: The effective dose of 18FDHT in women was 0.020 ± 0.001 mSv/MBq and the critical organ was the urinary bladder, which received an equivalent dose of 0.061 ± 0.024 mSv/MBq. No change was found in effective dose or equivalent dose to the critical organ in patients on therapy for ER+/AR+ breast cancer versus baseline. A small, but statistically significant change, was found for 18FDHT activity in the liver and the equivalent dose to the liver and GI tract.