Multiply radioiodinated somatostatin analogs induce receptor-specific cytotoxicity

被引:16
|
作者
Meyers, MO [1 ]
Anthony, CT
Coy, DH
Murphy, WA
Drouant, GJ
Fuselier, J
Espenan, GD
Maloney, TJ
Woltering, EA
机构
[1] Louisiana State Univ, Med Ctr, Dept Surg, New Orleans, LA 70112 USA
[2] Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA
[3] Vet Adm Med Ctr, New Orleans, LA 70146 USA
[4] Tulane Univ, Med Ctr, New Orleans, LA USA
[5] Louisiana State Univ, Med Ctr, Dept Radiol, New Orleans, LA 70112 USA
[6] Med Ctr Louisiana New Orleans, Dept Nucl Med, New Orleans, LA 70112 USA
[7] Iso Tex Inc, Friendswood, TX USA
关键词
somatostatin; somatostatin receptor; cytotoxicity; radiolabeled iodine; (125)iodine; neuroblastoma; pancreatic carcinoma; peptide;
D O I
10.1006/jsre.1998.5313
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background 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, I-125-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 I-125-WOC 4a, in a somatostatin receptor subtype-2 (sst 2)-expressing human neuroblastoma cell Line to its cytotoxicity in a somatostatin receptor-negative human pancreatic carcinoma cell line. Methods. IMR-32 neuroblastoma cells (sst a-positive) and PANC-1 human pancreatic cells (sst a-negative) were incubated with I-125-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,I-125-WOC 4a (1 cpm/cell) alone,I-125-WOC 4a with 10(-6) M octreotide acetate,I-125 (1 cpm/ cell) alone,I-125 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. Results. Following short-term exposure, I-125-WOC 4, induced dose-dependent cytotoxicity in IMR-32 cells (P < 0.05 by ANOVA), but not in the PANC-1 cells. After exposure to I-125-WOC 4, (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 I-125 alone or I-125 with 10-6 M octreotide acetate. Simultaneous exposure to I-125-WOC 4a and octreotide acetate was also cytotoxic. Conclusion. I-125-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. (C) 1998 Academic Press.
引用
收藏
页码:154 / 158
页数:5
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