Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, Vienna, Austria.
J Nucl Med. 2023 Nov;64(11):1730-1736. doi: 10.2967/jnumed.123.265980. Epub 2023 Sep 21.
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. Men ( = 112) with histologically proven prostate cancer who underwent Ga-PSMA-HBED-CC (Ga-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. ADT was associated with lower levels of PSMA uptake in the kidneys (SUV: Δ[ADT - control] = -7.89; 95% CI, -10.73 to -5.04; < 0.001), liver (SUV: Δ[ADT - control] = -2.3; 95% CI, -5.72 to -0.93; = 0.003), spleen (SUV: Δ[ADT - control] = -1.27; 95% CI, -3.61 to -0.16; = 0.033), and salivary glands (SUV: Δ[ADT - control] = -1.04; 95% CI, -2.48 to -0.13; = 0.027). In a multivariate analysis, ADT was found to be associated with lower renal (SUV: β = -7.95; 95% CI, -11.06 to -4.84; < 0.0001), hepatic (SUV: β = -7.85; 95% CI, -11.78 to -3.91; < 0.0001), splenic (SUV: β = -5.83; 95% CI, -9.95 to -1.7; = 0.006), and salivary gland (SUV: β = -1.47; 95% CI, -2.76 to -0.17; = 0.027) uptake. A higher glomerular filtration rate was associated with a higher renal SUV (β = 0.16; 95% CI, 0.05 to 0.26; = 0.0034). 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 Ac-labeled PSMA conjugates.
雄激素剥夺疗法 (ADT) 已知会影响前列腺特异性膜抗原 (PSMA) 在前列腺癌中的表达，这可能会使 PSMA 配体 PET 结果的解读复杂化，并影响 PSMA 放射性配体治疗。然而，ADT 对非肿瘤器官中 PSMA 配体生物分布的影响尚不清楚。
研究人员回顾性招募了 2015 年 11 月至 2021 年 7 月期间在维也纳医科大学接受 Ga-PSMA-HBED-CC（Ga-PSMA-11）PET/CT 检查且已知 ADT 状态的病理证实患有前列腺癌的 112 名男性。其中 56 名患者在成像时接受促性腺激素释放激素干扰 ADT（ADT 组），而 56 名无 ADT 史的患者作为对照组。对生理性 PSMA 表达器官（唾液腺、肾脏、肝脏和脾脏）进行描绘，并根据其数据分布比较其摄取情况。多变量回归分析评估了肾脏、肝脏、脾脏和唾液腺摄取与解释变量代谢肿瘤体积、肾小球滤过率和 ADT 状态之间的关系。
ADT 与肾脏（SUV：Δ[ADT-对照] = -7.89；95%CI，-10.73 至-5.04； ＜0.001）、肝脏（SUV：Δ[ADT-对照] = -2.3；95%CI，-5.72 至-0.93； ＝0.003）、脾脏（SUV：Δ[ADT-对照] = -1.27；95%CI，-3.61 至-0.16； ＝0.033）和唾液腺（SUV：Δ[ADT-对照] = -1.04；95%CI，-2.48 至-0.13； ＝0.027）摄取水平降低相关。多变量分析发现，ADT 与肾脏（SUV：β = -7.95；95%CI，-11.06 至-4.84； ＜0.0001）、肝脏（SUV：β = -7.85；95%CI，-11.78 至-3.91； ＜0.0001）、脾脏（SUV：β = -5.83；95%CI，-9.95 至-1.7； ＝0.006）和唾液腺（SUV：β = -1.47；95%CI，-2.76 至-0.17； ＝0.027）摄取降低相关。肾小球滤过率较高与肾脏 SUV 较高相关（β = 0.16；95%CI，0.05 至 0.26； ＝0.0034）。
这些发现表明，ADT 全身性地调节 PSMA 表达，这可能对 PSMA 放射性配体治疗的治疗优化和副作用最小化策略产生影响，特别是对于使用更有效的 Ac 标记 PSMA 缀合物的治疗。
