Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice

Abstract

Purpose: The aim of this study was to analyze the effect therapeutic injections of (177)Lu-DOTA(0)-Tyr(3)]-octreotate (DOTATATE) had on the tumor uptake of a subsequent injection with (111)In-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 (177)Lu-DOTATATE. At various intervals thereafter (4-13 days), a second injection with (111)In-DOTATATE (0.5 MBq) was given. One (1) day after the second injection, the animals were sacrificed, tumor tissues collected, the tumor (111)In and (177)Lu activity concentration determined, and tumor regression/cell density was recorded.

Results: In animals given curative amounts, the uptake of (111)In 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 (177)Lu 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.