Meyers M O, Anthony C T, Coy D H, Murphy W A, Drouant G J, Fuselier J, Espenan G D, Maloney T J, Woltering E A
Department of Surgery, Louisiana State University Medical Center, New Orleans, USA.
J Surg Res. 1998 May;76(2):154-8. doi: 10.1006/jsre.1998.5313.
Radiolabeled somatostatin analogs have gained popularity for tumor imaging and have recently been used for the treatment of somatostatin receptor-expressing tumors. We have developed a novel, N-terminally extended, multiply iodinated somatostatin analog, 125I-WOC 4a, that we hypothesize will be a useful tool for the detection of and therapy for somatostatin receptor-positive tumors. To evaluate the therapeutic potential of this agent, we compared the cytotoxicity of 125I-WOC 4a in a somatostatin receptor subtype-2 (sst 2)-expressing human neurobalstoma cell line to its cytotoxicity in a somatostatin receptor-negative human pancreatic carcinoma cell line.
IMR-32 neuroblastoma cells (sst 2-positive) and PANC-1 human pancreatic cells (sst 2-negative) were incubated with 125I-WOC 4a at doses ranging from 0.1-100 CPM/cell for 48 h and cell viability was assessed by a colorimetric (MTT) cell viability assay. Subsequently, IMR-32 cells were incubated with either control medium, 125I-WOC 4a (1 cpm/cell) alone, 125I-WOC 4a with 10(-6) M octreotide acetate, 125I (1 cpm/cell) alone, 125I with octreotide acetate, or octreotide acetate alone for 48 h, washed, and cryopreserved for 4 weeks. Cells were then thawed, replated, and allowed to acclimate for 48 h. Cell viability was assessed by trypan blue exclusion and a colorimetric assay.
Following short-term exposure, 125I-WOC 4a induced dose-dependent cytotoxicity in IMR-32 cells (P < 0.05 by ANOVA), but not in the PANC-1 cells. After exposure to 125I-WOC 4a (1 cpm/cell) for 48 h followed by a 4-week cryopreserved exposure, significant cytotoxicity was induced in IMR-32 cells (P < 0.05 by ANOVA) which was not seen in cells treated with 125I alone or 125I with 10(-6) M octreotide acetate. Simultaneous exposure to 125I-WOC 4a and octreotide acetate was also cytotoxic.
125I-WOC 4a induces receptor-specific cytotoxicity following both short- and long-term drug exposures. This radiopharmaceutical may be useful for localizing or treating somatostatin receptor-positive tumors.
