Comparison of [ 177 Lu-DOTA 0,Tyr 3 ]-Octreotate and [ 177 Lu-DOTA 0,Tyr 3 ]-Octreotide for Receptor-Mediated Radiation Therapy of the Xenografted Human Midgut Carcinoid Tumor GOT1

The aim of this study was to compare the tumor uptake versus time and the tumor response in nude mice transplanted with a human midgut carcinoid (GOT1), when treated with either [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotide or [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotate and to evaluate if plasma chromogranin A (P-CgA) was a reliable marker of tumor response. The tumor uptake and retention of activity of a single intravenous (i.v.) dose (15 MBq) of [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotate or [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotide were compared in nude mice xenografted with GOT1. The activity concentration 24 hours after injection was significantly higher in animals given [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotate versus [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotide (16% ± 1.4% of injected activity per gram [%IA/g] vs. 8.1% ± 2.1% IA/g, mean ± standard error of the mean) (p = 0.00061). The mean absorbed dose was higher in animals given [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotate (46 ± 4.3 vs. 17 ± 3.4 Gy). The reduction of tumor volume was accordingly more prominent in animals given [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotate than in animals given [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotide (p = 0.003). The mean tumor volume for animals given [¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotate was reduced to 3% of its initial value. P-CgA values were strongly correlated with tumor volume. Octreotate seems to be a more suitable somatostatin analog than octreotide for receptor-mediated radiation therapy. P-CgA is a simple, accurate method for the estimation of tumor response in this animal model.