Synthesis and Evaluation of Bombesin Derivatives on the Basis of Pan
[CANCER RESEARCH 64, 6707–6715, September 15, 2004] Synthesis and Evaluation of Bombesin Derivatives on the Basis of Pan-Bombesin Peptides Labeled with Indium-111, Lutetium-177, and Yttrium-90 for Targeting Bombesin Receptor-Expressing Tumors Hanwen Zhang,1 Jianhua Chen,1 Christian Waldherr,1 Karin Hinni,1 Beatrice Waser,2 Jean Claude Reubi,2 and Helmut R. Maecke1 1Division of Radiological Chemistry, Institute of Nuclear Medicine, Department of Radiology, University Hospital, Basel; and 2Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland ABSTRACT promising targets for molecular imaging and targeted therapy of cancer, because they are located on the plasma membrane and, upon Bombesin receptors are overexpressed on a variety of human tumors binding of a ligand, the receptor-ligand complex is internalized. These like prostate, breast, and lung cancer. The aim of this study was to develop findings were the basis for the development of diagnostic and thera- radiolabeled (Indium-111, Lutetium-177, and Yttrium-90) bombesin an- alogues with affinity to the three bombesin receptor subtypes for targeted peutic radiopeptides useful in peptide receptor scintigraphy and tar- radiotherapy. The following structures were synthesized: diethylenetri- geted radiotherapy (5–10). Among the most relevant peptide recep- aminepentaacetic acid-␥-aminobutyric acid-[D-Tyr6, -Ala11, Thi13, Nle14] tors, the bombesin receptors are of major interest, because they were bombesin (6–14) (BZH1) and 1,4,7,10-tetraazacyclododecane-N,N,N؆,Nٟ found to be overexpressed in various important cancers like prostate -tetraacetic acid-␥-aminobutyric acid-[D-Tyr6, -Ala11, Thi13, Nle14] (11, 12), breast (13, 14), and small cell lung cancer (15).
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