Progressive nuclear translocation of somatostatin analogs.
Optimal cancer radiotherapy using Auger electron emitters requires selective localization of radionuclides in close proximity to tumor DNA.


METHODS
Intracellular trafficking of (125)I-Tyr1-somatostatin-14 somatotropin-release inhibiting factor (SRIF) and 2 of its analogs, (125)I-WOC 4a and (111)In-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.


CONCLUSIONS
These in vitro studies show that prolonged exposure to radiolabeled SRIF analogs significantly 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 radiotherapy.
Hornick
C A
CA
Department of Physiology, The Stanley S. Scott Cancer Center, New Orleans, Louisiana, USA.
Anthony
C T
CT
Hughey
S
S
Gebhardt
B M
BM
Espenan
G D
GD
Woltering
E A
EA
D002467:Cell Nucleus / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D006801:Humans; D007204:Indium / Q000493:pharmacokinetics; D009447:Neuroblastoma / Q000378:metabolism* / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D011485:Protein Binding; D013004:Somatostatin / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D004273:DNA, Neoplasm; D009942:Organometallic Compounds; D007204:Indium; D014443:Tyrosine; D013004:Somatostatin; C081788:pentetreotide