Changes of Prostate-Specific Membrane Antigen-Radioligand Uptake on PET with Systemic Therapy in Patients with Metastatic Renal Cell Carcinoma

<b>Background/Objectives</b>: Early treatment assessment in metastatic renal cell carcinoma (mRCC) remains challenging due to the limited accuracy of current imaging methods. Given prostate-specific membrane antigen (PSMA) overexpression in mRCC, PSMA PET is a promising approach. Despite numerous studies on PSMA imaging in mRCC, data on PSMA uptake changes during systemic therapy are scarce. We analyzed PSMA uptake on PET after treatment initiation in mRCC patients. <b>Methods</b>: A retrospective single-center analysis of mRCC patients who underwent [¹⁸F]PSMA-1007 PET/CT before (PET₁) and at a mean of 9.5 weeks after (PET₂) starting systemic therapy was conducted. PSMA uptake in metastatic lesions was compared by region and RCC subtype. Uptake differences between PET₁ and PET₂ were analyzed using an unpaired <i>t</i>-test. <b>Results</b>: This study included 25 patients (mean age 65.2 ± 14.7 years; 20 male) with mRCC. A total of 113 (PET₁) and 48 (PET₂) metastases were assessed. Lymph node metastases showed stable PSMA uptake (median SUV_max) after treatment (7.8 vs. 7.7, <i>p</i> = 0.77), while uptake by bone (6.4 vs. 12.4, <i>p</i> = 0.03) and lung metastases (4.5 vs. 8.1, <i>p</i> = 0.004) increased significantly. SUV stability in lymph nodes was independent of RCC subtype (ccRCC: <i>p</i> = 0.48, pRCC: <i>p</i> > 0.99). Bone (6.6 vs. 15.9, <i>p</i> = 0.008) and lung metastases (4.8 vs. 8.1, <i>p</i> = 0.02) had higher PSMA uptake in ccRCC, unlike pRCC (bone: 6.2 vs. 6.0, <i>p</i> = 0.86). <b>Conclusions</b>: Alterations of PSMA-radioligand uptake are seen in bone and pulmonary metastases but not in lymph node metastases after initiation of systemic treatment in patients with mRCC. ccRCC has a higher PSMA uptake than other RCC subtypes.