Baseline [ 68 Ga]Ga-PSMA-11 PET/CT before [ 177 Lu]Lu-PSMA-617 Radioligand Therapy: Value of PSMA-Uptake Thresholds in Predicting Targetable Lesions.

Baseline uptake on prostate-specific membrane antigen (PSMA)-targeted imaging is a prerequisite for radioligand therapy (RLT) with [ 177 Lu]Lu-PSMA-617. This study aims to quantify lesion-based response to RLT in relation to pretreatment standard molecular imaging metrics derived from [ 68 Ga]Ga-PSMA-11 PET/CT. Sixty-one patients with mCRPC underwent [ 68 Ga]Ga-PSMA-11 PET/CT imaging before and after a median of 4 (IQR 2-6) RLT cycles. Maximum and mean standardized uptake values (SUV max , SUV mean ), as well as tumor-to-liver ratio (TLR), were assessed. A median of 12 (IQR 7-17) lesions was analyzed per patient, resulting in a total of 718 lesions. Lesions with ≥30% SUV max decline or falling below the blood pool uptake were considered responsive; ≥30% SUV max increase marked lesion progression. Additionally, 4-point visual scoring was performed according to E-PSMA consensus. In total, 550/718 (76.6%) lesions responded to RLT, including 389/507 (76.7%) bone metastases and 143/181 (79.0%) lymph node metastases. Baseline SUV max , SUV mean , and TLR values were associated with lesion response by a moderate but significant correlation (r s = 0.33, p < 0.001, r s = 0.32, p < 0.001, and r s = 0.31, p < 0.001, respectively). For the classification of lesion progression based on baseline PSMA uptake, receiver operating characteristics (ROC) found SUV max , SUV mean , and TLR to have comparable discriminatory value (AUC 0.85, 0.87, and 0.83). Of 42 tumor sites with baseline uptake below the liver (V-score < 2), 19/42 (45.2%) were responsive, 9/42 (21.4%) were stable, and 14/42 (33.3%) showed progression, leaving liver uptake a threshold with low prognostic value for the identification of RLT-refractory lesions (PPV 33%). This was observed accordingly for various liver uptake-based thresholds, including TLR < 1.5, <2.0 with a PPV at 24%, 20%, respectively. Standard uptake parameters quantified by routine baseline [ 68 Ga]Ga-PSMA-11 PET/CT are moderately associated with post-treatment lesion response to [ 177 Lu]Lu-PSMA-617. Commonly applied liver-based uptake thresholds have limited value in predicting refractory lesions at individual tumor sites.