Background: Peptide receptor radionuclide therapy (PRRT) capitalizes on somatostatin receptor (SSR) overexpression on NETs to deliver targeted isotope therapy. Objective prediction of efficacy remains to be established. Functional imaging of SSR expression (SRE) is used as a predictor of efficacy. Biomarkers e.g. circulating CgA, are ineffective. Circulating NET transcript analysis (NETest) integrated with tumor grade provides a Predictive Quotient Index (PQI) of PRRT. We validated the utility of this PRRT complementary diagnostic in a prospective, blinded study. Methods:¹⁷⁷Lu-PRRT (29.1±2.2 GBq). NETs (n= 35); with progressive disease (66%). Baseline evaluations: Clinical status, Grade (Ki67), SRE, CgA (NeoLisa, ULN > 108ng/ml), and NETest (qRT-PCR - multianalyte algorithmic analyses, ULN > 14%). PQI: “omic” NETest gene expression (regulating metabolism and growth factor signaling) mathematically combined with Ki67 index. PQI has two prediction outputs: “responder” (R) vs “non-responder” (NR). Disease control was by RECIST criteria (R vs NR). All samples were blinded. Statistics: Cox proportional multiple regression, Kaplan-Meier survival, & McNemar-test. Results: At restaging, the overall response (disease control rate) was 77%; median PFS not reached (follow-up 4-13 months). Histology: GI: 5; GII: 21; GIII 1; and lung: TC: 2; AC: 5. SRE was Grade 3 (80%). Baseline CgA was 1556±1454ng/ml (89% elevated) and NETest was 60±21% (100% elevated) respectively. Predictive accuracies of SRE, clinical status, CgA levels ( > 2ULN) and NETest ranged from 25-54% (not-significant). PQI was the only predictive marker by multivariate analysis (p= 0.002). The PQI diagnostic was 92% concordant with outcome and significantly more accurate than all other markers (McNemar: p< 0.002). Cox-proportional modeling confirmed PQI utility (OR: 9.1, p< 0.004). K-MS analysis identified significantly different mPFS between R (not reached) and NR (9.3 months; HR: 8.3, p< 0.0005). Conclusions: A pre-PRRT analysis of circulating NET genes, the predictive quotient index comprising “omic” analysis and grading, is validated to predict the efficacy of PRRT therapy in GEP and lung NETs.