Background: PRRT uses somatostatin receptor (SSR) expression on neuroendocrine tumors (NET) to deliver radiotherapy. Pretreatment patient stratification for response remains a key unmet need. NET transcript expression in blood integrated with tumor grade provides a PRRT predictive quotient (PPQ). This study validates the clinical utility for PRRT. Methods: Development and validation was undertaken in 3 independent ¹⁷⁷Lu-PRRT-cohorts. Specificity and prognostic value was tested in two somatostatin analog-treated and untreated patients. Developmental cohort: lung and gastroenteropancreatic [GEP] NETs (n= 72). The majority were GEP (71%), low grade (86% G1-G2). Prospective validation cohorts (n= 42-44) were well differentiated, low grade (86-95%) lung and GEP-NETs. SSA Cohort I n= 28 (100% low grade, 100% GEP-NET); SSA Cohort II n= 51 (98% low grade; 76% GEP-NET) and an untreated cohort n= 44 (64% low grade; 91% GEP-NET). NET blood gene transcripts (n= 8: growth factor signaling and metabolism) were measured pre-therapy and integrated with tumor Ki67 using a logistic regression model with a binary output: “predicted responder” (PPQ+); “predicted non-responder” (PPQ-). Response was evaluated using RECIST criteria [Responder (stable, partial/complete response) vs Non-Responder)]. All measurements and analyses were blinded. Statistics included Kaplan-Meier survival and test evaluation analyses. Results: Developmental cohort, 56% responded to PRRT. The PPQ predicted 100% of responders and 84% of non-responders (accuracy: 93%). In two validation cohorts (response: 64-79%), PPQ was 95% accurate (PPQ+ = 94-97%, PPQ- = 93-100%). Overall, median PFS was not reached in PPQ+ vs PPQ- (10-14 months; HR: 18-77, p< 0.0001). In comparator cohorts, the predictor (PPQ) was 47-50% accurate for SSA-treatment and 50% as a prognostic. No differences in PFS were respectively noted (PPQ+: 10-12 months vs. PPQ-: 9-15 months). Conclusions: The PPQ derived from circulating NET specific genes and tumor grade prior to the initiation of therapy is a highly specific predictor of the efficacy of PRRT with an accuracy of 95%.