Purpose: The aim of this study was to analyze the effect therapeutic injections of 177Lu-DOTA0-Tyr3]-octreotate (DOTATATE) had on the tumor uptake of a subsequent injection with 111In-DOTATATE in GOT1-bearing nude mice. Methods and Materials: Nude mice, xenografted with the human midgut carcinoid, GOT1, were first intravenously injected with a curative (30 MBq) or a suboptimal (7.5 MBq) amount of 177Lu-DOTATATE. At various intervals thereafter (4–13 days), a second injection with 111In-DOTATATE (0.5 MBq) was given. One (1) day after the second injection, the animals were sacrificed, tumor tissues collected, the tumor 111In and 177Lu activity concentration determined, and tumor regression/cell density was recorded. Results: In animals given curative amounts, the uptake of 111In was lower than in untreated animals. On the other hand, a second late injection (3–13 days) after suboptimal amounts resulted in a twofold higher tumor activity concentration versus untreated animals. When the uptake of the curative injection was corrected for tumor cell density, which decreased from 66% to 4% over 2 weeks, an enhanced uptake per tumor cell was observed. The curative and suboptimal amounts resulted in a different uptake and retention of 177Lu in tumors. The suboptimal amount resulted in a constant activity concentration, while the curative amount resulted in an increased activity concentration over time. Conclusions: Our results, as presented in this paper, describe how the second injection in a fractionation protocol will be affected by the first therapeutic amount. This new information might be useful in the optimization of radionuclide therapy.
