Purpose/Objective(s) To explore the relationship between 177Lu-D administered activity (AA), radiation dose absorbed and outcomes. Materials/Methods A prospective multi-center study was conducted to evaluate outcomes of pts with progressive, primary site agnostic, metastatic neuroendocrine tumors, Ki 67≤30%, adequate organ function, ECOG ≤2 & 68Ga-D PET confirmed overexpression of somatostatin receptor. The intervention consisted of 177Lu-D x 4 cycles (C) (6-12 wk intervals) with planned personalization based on individualized dosimetry. Planar and SPECT images were acquired at 4, 24 & 72 hrs following each cycle. Renal absorbed dose with a target threshold of ≤23 Gy after 4 cycles was used to personalize prescriptions. AA was standardized at 200 mCi for C1. This was adjusted for C2-4 with a max of 300 mCi/cycle. When individualized dosimetry images were not acquired, a standard 200 mCi was used. Additional dose adjustments were made based on considerations of hematologic, renal function and/or other adverse events. The study primary objective was progression free survival (PFS) at 12 months. A secondary objective was RECIST tumor response. To examine the relationship between AA, radiation dose absorbed and pt outcomes, we limited the analysis to pts where dosimetry scans were acquired for all 4 cycles. Pts were divided into 3 AA subgroups: A (escalated >880 mCi), B (standard 800 ± 10%), & C (de-escalated <720 mCi). Normal tissue & tumor absorbed doses were computed and differences tested using Kruskal Wallis (response) & Kaplan Meier (survival). Results 195 pts were enrolled; 177 pts received at least 1C 177Lu-D Time of first data lock was selected when all pts were eligible for a minimum of 12 month follow up. 142 (80.2%) pts received all 4 C; 90 pts had complete dosimetry performed and are the focus of this report. No. of pts in groups A, B, & C were 65, 10, & 15; mean AAs were 1052.6 (SD ± 80), 823.1 (SD ± 46.8) and 588.9 (SD ± 123.1) mCi, respectively. The mean radiation absorbed doses for kidney (left as reference) were 15.2 (SD ± 4.5), 20.5 (SD ± 4.3) & 16.8 (SD ± 3.7) Gy (P = 0.002); tumor doses were 86.1 (SD ± 55.4), 61.4 (SD ± 36) & 83.3 (SD ± 63.7) Gy (P = 0.37) respectively. Mean bone marrow absorbed dose was 1.01 (SD ± 1.14) Gy with no significant difference across the groups. Disease control rates (best response: CR, PR or SD) were 92.3% (A: 60/65), 60% (B: 6/10) and 73.3% (C: 11/15). Best response was PD for 7.7% (A: 5/60), 40% (B: 4/10) and 26.7% (C: 4/15) (P = 0.03). The PFS (95% CI) at 12 months was A: 95 (90-100)%, B:90 (73-100)%: and C:93 (82-100)% (P = 0.47). Conclusion A significant increase in best response for the dose escalation group was observed. However, there was no corresponding improvement in PFS at 12 months with this modest dose escalation regimen.