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Progressive Nuclear Translocation of Somatostatin Analogs

Departments of Physiology, Pathology, Surgery, Ophthalmology, and Radiology, The Stanley S. Scott Cancer Center
Neuroscience Center of Excellence, Louisiana State University Medical Center, New Orleans
Veterans Administration Medical Center, New Orleans, Louisiana

Correspondence: For correspondence or reprints contact: Eugene A. Woltering, MD, Medical Center at New Orleans, 1542 Tulane Ave., T7-1, New Orleans, LA 70112.

ABSTRACT

Optimal cancer radiotherapy using Auger electron emitters requires selective localization of radionuclides in close proximity to tumor DNA. Methods: Intracellular trafficking of ¹²⁵I-Tyr¹-somatostatin-14 somatotropin-release inhibiting factor (SRIF) and 2 of its analogs, ¹²⁵I-WOC 4a and ¹¹¹In-pentetreotide, was studied in human neuroblastoma cells. Results: After 24-h incubation, SRIF was degraded or recycled, whereas its protease-resistant analogs progressively accumulated in nuclear fractions. ¹¹¹ In-pentetreotide binding to DNA increased over time in somatostatin receptor-positive cells but not in somatostatin receptor-negative cells. Conclusion: These in vitro studies show that prolonged exposure to radiolabeled SRIF analogs significantly increases their cellular intemalization, nuclear translocation, and DNA binding. Clinically, infusion of radiolabeled somatostatin analogs may enhance tumor uptake and retention and provide more effective in situ radiotherapy.

Key Words: somatostatin • membrane receptor • DNA binding • endocytosis • in situ radiotherapy

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