Progressive nuclear translocation of somatostatin analogs

Optimal cancer radiotherapy using Auger electron emitters requires selectiv e localization of radionuclides in close proximity to tumor DNA. Methods: I ntracellular trafficking of I-125-Tyr(1)-somatostatin-14 somatotropin-relea se inhibiting factor (SRIF) and 2 of its analogs, I-125-WOC 4a and In-111-p entetreotide, 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. In-111-pentetreotid e binding to DNA increased overtime in somatostatin receptor-positive cells but not in somatostatin receptor-negative cells. Conclusion: These in vitr o studies show that prolonged exposure to radiolabeled SRIF analogs signifi cantly increases their cellular internalization, nuclear translocation, and DNA binding. Clinically, infusion of radiolabeled somatostatin analogs may enhance tumor uptake and retention and provide more effective in situ radi otherapy.