RT Journal Article SR Electronic T1 Antihormonal-Treatment Status Affects 68Ga-PSMA-HBED-CC PET Biodistribution in Patients with Prostate Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1730 OP 1736 DO 10.2967/jnumed.123.265980 VO 64 IS 11 A1 Kluge, Kilian A1 Haberl, David A1 Einspieler, Holger A1 Rasul, Sazan A1 Gutschmayer, Sebastian A1 Kenner, Lukas A1 Kramer, Gero A1 Grubmüller, Bernhard A1 Shariat, Shahrokh A1 Haug, Alexander A1 Hacker, Marcus YR 2023 UL http://jnm.snmjournals.org/content/64/11/1730.abstract AB Androgen deprivation therapy (ADT) is known to influence the prostate-specific membrane antigen (PSMA) expression of prostate cancer, potentially complicating the interpretation of PSMA ligand PET findings and affecting PSMA radioligand therapy. However, the impact of ADT on PSMA ligand biodistribution in nontumorous organs is not well understood. Methods: Men (n = 112) with histologically proven prostate cancer who underwent 68Ga-PSMA-HBED-CC (68Ga-PSMA-11) PET/CT between November 2015 and July 2021 at the Medical University Vienna with known ADT status were retrospectively recruited. Fifty-six patients were on gonadotropin-releasing hormone–interfering ADT at the time of imaging (ADT group), whereas 56 patients with no history of ADT served as a control group. Physiologically PSMA-expressing organs (salivary glands, kidneys, liver, and spleen) were delineated, and their uptake was compared according to their data distributions. Multivariate regression analysis assessed the relationship between renal, hepatic, splenic, and salivary gland uptake and the explanatory variables metabolic tumor volume, glomerular filtration rate, and ADT status. Results: ADT was associated with lower levels of PSMA uptake in the kidneys (SUVmean: Δ[ADT − control] = −7.89; 95% CI, −10.73 to −5.04; P < 0.001), liver (SUVpeak: Δ[ADT − control] = −2.3; 95% CI, −5.72 to −0.93; P = 0.003), spleen (SUVpeak: Δ[ADT − control] = −1.27; 95% CI, −3.61 to −0.16; P = 0.033), and salivary glands (SUVmean: Δ[ADT − control] = −1.04; 95% CI, −2.48 to −0.13; P = 0.027). In a multivariate analysis, ADT was found to be associated with lower renal (SUVmean: β = −7.95; 95% CI, −11.06 to −4.84; P < 0.0001), hepatic (SUVpeak: β = −7.85; 95% CI, −11.78 to −3.91; P < 0.0001), splenic (SUVpeak: β = −5.83; 95% CI, −9.95 to −1.7; P = 0.006), and salivary gland (SUVmean: β = −1.47; 95% CI, −2.76 to −0.17; P = 0.027) uptake. A higher glomerular filtration rate was associated with a higher renal SUVmean (β = 0.16; 95% CI, 0.05 to 0.26; P = 0.0034). Conclusion: These findings suggest that ADT systemically modulates PSMA expression, which may have implications for treatment-optimizing and side-effect–minimizing strategies for PSMA radioligand therapies, particularly those using more potent 225Ac-labeled PSMA conjugates.