Peptide Receptor Radionuclide Therapy (PRRT) with (177)Lu-DOTATATE; Differences in Tumor Dosimetry, Vascularity and Lesion Metrics in Pancreatic and Small Intestinal Neuroendocrine Neoplasms

SIMPLE SUMMARY: Patients suffering from disseminated, progressive, neuroendocrine neoplasms with a sufficient amount of somatostatin receptors and good kidney function can be treated with radioactive hormone-like molecules to prolong their life. In this study, the radioactivity in one tumor per patient at each treatment cycle was calculated and compared between 23 patients with pancreatic and 25 patients with small intestinal neuroendocrine neoplasia. Both types of tumors absorb a larger amount of radioactivity during early cycles that subsequently decline in the later cycles. This finding was more pronounced in the pancreatic tumors, which also expressed higher blood perfusion in the early cycles, known to facilitate the effect of radiation. This could be part of the reason why the pancreatic tumors shrunk more rapidly than the small intestinal ones. Our results also imply that increased administered activity in the early therapy cycles may be beneficial, at least in pancreatic neuroendocrine tumor patients. ABSTRACT: Dosimetry during peptide receptor radionuclide therapy (PRRT) has mainly focused on normal organs and less on the tumors. The absorbed dose in one target tumor per patient and several response related factors were assessed in 23 pancreatic neuroendocrine neoplasms (P-NENs) and 25 small-intestinal NEN (SI-NENs) during PRRT with (177)Lu-DOTATATE. The total administered activity per patient was (mean ± standard error of mean (SEM) 31.8 ± 1.9 GBq for P-NENs and 36 ± 1.94 GBq for SI-NENs. The absorbed tumor dose was 143.5 ± 2 Gy in P-NENs, 168.2 ± 2 Gy in SI-NENs. For both NEN types, a dose–response relationship was found between the absorbed dose and tumor shrinkage, which was more pronounced in P-NENs. A significant drop in the absorbed dose per cycle was shown during the course of PRRT. Tumor vascularization was higher in P-NENs than in SI-NENs at baseline but equal post-PRRT. The time to progression (RECIST 1.1) was similar for patients with P-NEN (mean ± SEM 30 ± 1 months) and SI-NEN (33 ± 1 months). In conclusion, a dose response relationship was established for both P-NENs and SI-NENs and a significant drop in the absorbed dose per cycle was shown during the course of PRRT, which warrants further investigation to understand the factors impacting PRRT to improve personalized treatment protocol design.