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Comparison of ¹¹¹In-labeled Somatostatin Analogues for Tumor Scintigraphy and Radionuclide Therapy¹

Department of Nuclear Medicine [M. d. J., W. A. P. B., W. H. B., P. P. M. K., B. F. B., E. P. K.] and Internal Medicine III [L. J. H., T. J. V., E. P. K.], University Hospital Dijkzigt, 3015 GD Rotterdam, the Netherlands; Mallinckrodt Medical, St. Louis, Missouri 63134 [A. S., M. A. S., J. L. E., J. E. B.]; and Department of Nuclear Medicine, Kantonspital Basel, CH-4031 Basel, Switzerland [H. R. M.]

We evaluated the following ¹¹¹In-labeled somatostatin (SS) analogues (diethylenetriaminepentaacetic acid, DTPA; tetraazacyclododecanetetraacetic acid, DOTA): [DTPA⁰]octreotide, [DTPA⁰,Tyr³]octreotide, [DTPA⁰,D-Tyr¹]octreotide, [DTPA⁰,Tyr³]octreotate [Thr(ol) in octreotide replaced with Thr], and [DOTA⁰,Tyr³]octreotide, in vitro and in vivo.

In vitro, all compounds showed high and specific binding to SS receptors in mouse pituitary AtT20 tumor cell membranes, and IC₅₀s were in the nanomolar range. Furthermore, all compounds showed specific internalization in rat pancreatic tumor cells; uptake of [¹¹¹In-DTPA⁰,Tyr³]octreotate was the highest of the compounds tested, and that of [¹¹¹In-DTPA⁰,D-Tyr¹]octreotide was the lowest. Biodistribution experiments in rats showed that, 4, 24, and 48 h after injection of [¹¹¹In-DTPA⁰,Tyr³]octreotide, [¹¹¹In-DTPA⁰,Tyr³]octreotate, and [¹¹¹In-DOTA⁰,Tyr³]octreotide, radioactivity in the octreotide-binding, receptor-expressing tissues and tumor-to-blood ratios were significantly higher than those after injection of [¹¹¹In-DTPA⁰]octreotide. Uptake of [¹¹¹In-DTPA⁰,Tyr³]octreotate in the target organs was also, in vivo, the highest of the radiolabeled peptides tested, whereas that of [¹¹¹In-DTPA⁰,D-Tyr¹]octreotide was the lowest. Uptake of [¹¹¹In-DTPA⁰,Tyr³]octreotide, [¹¹¹In-DTPA⁰,Tyr³]octreotate, and [¹¹¹In-DOTA⁰,Tyr³]octreotide in target tissues was blocked by >90% by 0.5 mg of unlabeled octreotide, indicating specific binding to the octreotide receptors. Blockade of [¹¹¹In-DTPA⁰,D-Tyr¹]octreotide was >70%. In conclusion, radiolabeled [DTPA⁰,Tyr³]octreotide and, especially, [DTPA⁰,Tyr³]octreotate and their DOTA-coupled counterparts are most promising for scintigraphy and radionuclide therapy of SS receptor-positive tumors in humans.

¹ This work was supported by Swiss National Science Foundation Grant 31-42516/94 and the "Regionale Krebsliga beider Basel" (both to H. R. M.).

² To whom requests for reprints should be addressed, at Department of Nuclear Medicine, V220, University Hospital Rotterdam, 3015 GD Rotterdam, the Netherlands. Phone: 31 10 4635781; Fax: 31 10 4635997; E-mail: dejong@nuge.azr.nl.

Received 8/ 6/97. Accepted 12/ 3/97.

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