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Experimental radiotherapy of receptor‐positive human prostate adenocarcinoma with 188 Re‐RC‐160, a directly‐radiolabeled somatostatin analogue
Author(s) -
Zamora Paul O.,
Gulhke Stefan,
Bender Hans,
Diekmann Daniella,
Rhodes Buck A.,
Biersack HansJurgen,
Knapp F. F. Russ
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960117)65:2<214::aid-ijc15>3.0.co;2-d
Subject(s) - somatostatin receptor , somatostatin , radiation therapy , adenocarcinoma , prostate , medicine , cancer research , prostate adenocarcinoma , receptor , endocrinology , chemistry , oncology , cancer
The therapeutic potential of the somatostatin analogue RC‐160 radiolabeled with 188 Re was evaluated in nude mice bearing xenografts of human prostate adenocarcinoma. 188 Re‐RC‐160 was selectively retained in both DU‐145 and PC‐3 tumors following direct intra‐tumor injection at all time points examined (2, 6 and 24 hr post‐injection). Unbound 188 Re‐RC‐160 was rapidly excreted via the hepatobiliary system and, with the exception of the gastrointestinal tract, very little normal organ uptake was found at any time point examined. Negative control compounds, 188 Re‐perrhenate and 188 Re‐mercaptoacetyl‐triglycine ( 188 Re‐MAG3), were essentially washed out of the tumor by 6 hr post‐injection and were rapidly excreted through the kidneys. 131 I‐RC‐160, used as a reference compound, had a biodistribution in tumor‐bearing animals similar to that of 188 Re‐RC‐160. In PC‐3 xenografts, 188 Re‐RC‐160 gave a dose‐dependent therapeutic response (stasis or regression) even in animals with relatively large tumor masses (greater than 600 mm 3 ), whereas the macro‐aggregated form of 188 Re‐RC‐160 did not. Long‐term studies with 188 Re‐RC‐160 demonstrated a protracted reduction of tumor volume and a positive effect on animal survival. Neither RC‐160 by itself nor a 188 Re‐labeled peptide, unrelated to somatostatin (PA‐22‐2, a laminin peptide), demonstrated the reduction in tumor mass observed with 188 Re‐RC‐160. 188 Re‐RC‐160 shows potential as a new clinical agent for treatment of somatostatin‐receptor‐positive cancers. © 1996 Wiley‐Liss, Inc.