Antitumor and antiangiogenic effects of somatostatin receptor-targeted in situ radiation with (111)In-DTPA-JIC 2DL.
BACKGROUND
Expression of somatostatin receptor subtype 2 (sst 2) in angiogenic tumor vessels appears to be homogeneous, while tumor cell expression of this receptor is often heterogeneous. We have developed a novel in vitro three-dimensional tumor angiogenesis model to study the antitumor and the antiangiogenic effects of radiolabeled somatostatin analogs. We hypothesized that targeted in situ radiation with an Auger electron-emitting radiolabeled somatostatin analog would produce receptor-specific cytotoxicity in sst 2-expressing cells.


METHODS
IMR-32 human neuroblastoma (sst 2-positive) and MDA MB-231 human breast cancer (sst 2-negative) xenografts were created in nude mice from monolayer cell cultures. Fragments of these tumors were embedded in three-dimensional fibrin gels supplemented with endothelial growth media and incubated for a period of 14 days. Tumor fragments were treated with 50 microCi/ml of (111)In-JIC 2DL, a sst 2-preferring somatostatin analog, or medium on Day 1. Initial angiogenic activity was determined at 48 h and the mean angiogenic score and tumoricidal responses were assessed on Day 14.


CONCLUSIONS
Tumoricidal effects of (111)In-JIC 2DL were seen only in sst 2-positive IMR-32 tumors. However, the angiogenic response was inhibited in both IMR-32 and MDA MB-231 tumors independent of the tumor cells' sst 2 status. Somatostatin receptor-mediated in situ radiation therapy has profound cytotoxic effects on angiogenic blood vessels and sst 2-expressing tumor cells.
Gulec
S A
SA
Department of Surgery, The Louisiana State University Health Sciences Center, New Orleans 70112, USA.
Drouant
G J
GJ
Fuselier
J
J
Anthony
C T
CT
Heneghan
J
J
DelCarpio
J B
JB
Coy
D H
DH
Murphy
W A
WA
Woltering
E A
EA
D000230:Adenocarcinoma; D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms; D003287:Contrast Media / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007205:Indium Radioisotopes / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000532:radiotherapy*; D009447:Neuroblastoma; D015282:Octreotide / Q000737:chemistry / Q000494:pharmacology; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D003287:Contrast Media; D007205:Indium Radioisotopes; D017481:Receptors, Somatostatin; D004369:Pentetic Acid; C093733:somatostatin receptor 2; D015282:Octreotide