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Targeted radiotherapy with [ 90 Y]‐SMT 487 in mice bearing human nonsmall cell lung tumor xenografts induced to express human somatostatin receptor subtype 2 with an adenoviral vector
Author(s) -
Rogers Buck E.,
Zinn Kurt R.,
Lin ChinYu,
Chaudhuri Tandra R.,
Buchsbaum Donald J.
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10300
Subject(s) - somatostatin receptor 2 , octreotide , medicine , somatostatin receptor , in vivo , somatostatin , genetic enhancement , receptor , radiation therapy , cancer research , radionuclide therapy , pathology , biology , gene , biochemistry , microbiology and biotechnology
BACKGROUND Novel approaches to increasing the therapeutic efficacy of targeted radiotherapy of cancer are required. One strategy to achieve this goal is to induce high‐level expression of a receptor on the surface of tumor cells that can be targeted with a radiolabeled peptide. The objectives of this study were to 1) induce somatostatin receptor (SSTr2) expression in tumor cells using an adenovirus encoding the SSTr2 gene (AdSSTr2), 2) demonstrate tumor localization of [ 111 In]‐DTPA‐ D ‐Phe 1 ‐octreotide in AdSSTr2‐injected tumors, and 3) show therapeutic efficacy with [ 90 Y]‐DOTA‐ D ‐Phe 1 ‐Tyr 3 ‐octreotide ([ 90 Y]‐SMT 487). METHODS SSTr2 expression was validated in vitro by the binding and subsequent internalization of [ 111 In]‐DTPA‐ D ‐Phe 1 ‐octreotide (21.3% per mg of total protein) in A‐427 cells infected with AdSSTr2. In vivo imaging confirmed 5‐ to 10‐fold greater uptake 5.5 hours after intravenous administration of [ 111 In]‐DTPA‐ D ‐Phe 1 ‐octreotide in AdSSTr2‐injected tumors relative to control tumors. For therapy studies, mice bearing established subcutaneous A‐427 tumors were given two intratumoral injections of AdSSTr2 1 week apart, followed by an intravenous injection of 400 μCi or 500 μCi [ 90 Y]‐SMT 487 at 2 and 4 days after each adenoviral administration. Control animals either were not treated or were administered 500 μCi [ 90 Y]‐SMT 487 with no AdSSTr2 injection. RESULTS These studies showed that untreated animals and animals treated with no virus and 500 μCi [ 90 Y]‐SMT 487 had median tumor quadrupling times of 16 and 25 days, respectively. Mice administered AdSSTr2 and either 400 μCi or 500 μCi of [ 90 Y]‐SMT 487 demonstrated significantly longer median tumor quadrupling times of 40 and 44 days, respectively ( P < 0.02). CONCLUSIONS These studies are the first to demonstrate in vivo therapeutic efficacy using a radiolabeled peptide targeted to a receptor expressed on the surface of tumor cells following gene transfer. Future studies will focus on the optimization of this approach. Cancer 2002;94:1298–1305. © 2002 American Cancer Society. DOI 10.1002/cncr.10300