The effect of drug dose and drug exposure time on the binding, internalization, and cytotoxicity of radiolabeled somatostatin analogs.
J Surg Res
; 119(1): 1-13, 2004 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-15126075
BACKGROUND: Creation of protease-resistant somatostatin analogs has allowed development of these peptides as clinically useful drugs. Widespread diagnostic use of radiolabeled somatostatin analogs has enhanced interest in the binding and intracellular distribution of these peptides. The degree of drug internalization and length of drug retention may be critical for drug-induced cytotoxicity. We hypothesized that the ability of a radiolabeled peptide to bind to a cell, be internalized, and induce cytotoxicity is proportional to both the radioligand concentration and the exposure time. MATERIALS AND METHODS: To test this hypothesis, somatostatin receptor-expressing cells (IMR-32) were incubated with (111)In-pentetreotide, a sst 2 preferring somatostatin analogue. Radioligand exposure time and/or concentration were varied. RESULTS: Prolonged exposure to a fixed concentration of radioligand resulted in progressive increases in whole cell binding and internalization over time. Cells exposed to a relatively fixed number of microCi-Hr yielded constant whole cell binding and internalization. Increasing the microCi-Hr resulted in a proportionate increase in binding. Cytotoxicity was also proportional to the dose of radiation regardless of whether the exposure was internalized radiation (microCi-Hr from (111)In-pentetreotide) or from external beam radiation (cGy). CONCLUSION: Both drug exposure time and drug concentration contribute to cell binding and cytotoxicity in this model and their relative contributions are inversely related.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Somatostatina
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Surg Res
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos