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

• 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.

Nyckelord

Animals

Carcinoid Tumor

metabolism

pathology

radiotherapy

Cell Line

Tumor

Dose-Response Relationship

Radiation

Humans

Indium Radioisotopes

pharmacokinetics

Injections

Intravenous

Lutetium

analysis

pharmacokinetics

Mice

Mice

Nude

Octreotide

administration & dosage

analogs & derivatives

pharmacokinetics

Organometallic Compounds

administration & dosage

pharmacokinetics

Radioisotopes

pharmacokinetics

Time Factors

Tumor Burden

Xenograft Model Antitumor Assays

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