Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Aug;85(15):5688–5692. doi: 10.1073/pnas.85.15.5688

Radioimmunoassay for octapeptide analogs of somatostatin: measurement of serum levels after administration of long-acting microcapsule formulations.

M Mason-Garcia 1, M Vaccarella 1, J Horvath 1, T W Redding 1, K Groot 1, P Orsolini 1, A V Schally 1
PMCID: PMC281825  PMID: 2899894

Abstract

The development of a long-acting delivery system for D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), an octapeptide analog of somatostatin, required the establishment of a method for determining the concentration of this analog in serum during treatment. A sensitive and specific radioimmunoassay (RIA) for RC-160 was developed and used for following the rate of liberation of this peptide from microcapsules of poly(DL-lactide-coglycolide). Antibodies were generated in a rabbit against RC-160 conjugated to bovine serum albumin with glutaraldehyde. At an antiserum dilution of 1:100,000, the antibodies bound approximately 25% of added radiolabeled RC-160. Somatostatin octapeptide analogs that had a disulfide bridge showed crossreactivity with the antiserum, but analogs without the disulfide bridge and other peptides tested did not crossreact. The minimum detectable dose of RC-160 was 10 pg. Intra- and interassay coefficients of variation ranged from 9.1% to 12.8% and from 14% to 30%, respectively. The RIA was suitable for direct determination of RC-160 in serum. Eleven prototype batches of microcapsules were tested in rats, and the rate of release of the analog from the microcapsules was followed. An improved batch of microcapsules made from RC-160 pamoate maintained high serum levels of RC-160 for more than 30 days after intramuscular injection. The RIA should be of value for monitoring levels of this analog in serum during long-term therapy.

Full text

PDF
5688

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asch R. H., Rojas F. J., Bartke A., Schally A. V., Tice T. R., Klemcke H. G., Siler-Khodr T. M., Bray R. E., Hogan M. P. Prolonged suppression of plasma LH levels in male rats after a single injection of an LH-RH agonist in poly(DL-lactide-co-glycolide) microcapsules. J Androl. 1985 Mar-Apr;6(2):83–88. doi: 10.1002/j.1939-4640.1985.tb00821.x. [DOI] [PubMed] [Google Scholar]
  2. Cai R. Z., Szoke B., Lu R., Fu D., Redding T. W., Schally A. V. Synthesis and biological activity of highly potent octapeptide analogs of somatostatin. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1896–1900. doi: 10.1073/pnas.83.6.1896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. D'Ercole A. J., Stiles A. D., Underwood L. E. Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci U S A. 1984 Feb;81(3):935–939. doi: 10.1073/pnas.81.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Daughaday W. H., Mariz I. K., Blethen S. L. Inhibition of access of bound somatomedin to membrane receptor and immunobinding sites: a comparison of radioreceptor and radioimmunoassay of somatomedin in native and acid-ethanol-extracted serum. J Clin Endocrinol Metab. 1980 Oct;51(4):781–788. doi: 10.1210/jcem-51-4-781. [DOI] [PubMed] [Google Scholar]
  5. Heber D., Odell W. D., Schedewie H., Wolfsen A. R. Improved iodination of peptides for radioimmunoassay and membrane radioreceptor assay. Clin Chem. 1978 May;24(5):796–799. [PubMed] [Google Scholar]
  6. Hierowski M. T., Liebow C., du Sapin K., Schally A. V. Stimulation by somatostatin of dephosphorylation of membrane proteins in pancreatic cancer MIA PaCa-2 cell line. FEBS Lett. 1985 Jan 7;179(2):252–256. doi: 10.1016/0014-5793(85)80529-9. [DOI] [PubMed] [Google Scholar]
  7. Karashima T., Cai R. Z., Schally A. V. Effects of highly potent octapeptide analogs of somatostatin on growth hormone, insulin and glucagon release. Life Sci. 1987 Aug 24;41(8):1011–1019. doi: 10.1016/0024-3205(87)90690-4. [DOI] [PubMed] [Google Scholar]
  8. Mason-Garcia M., Vigh S., Comaru-Schally A. M., Redding T. W., Somogyvari-Vigh A., Horvath J., Schally A. V. Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1547–1551. doi: 10.1073/pnas.82.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Paz-Bouza J. I., Redding T. W., Schally A. V. Treatment of nitrosamine-induced pancreatic tumors in hamsters with analogs of somatostatin and luteinizing hormone-releasing hormone. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1112–1116. doi: 10.1073/pnas.84.4.1112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Redding T. W., Schally A. V., Tice T. R., Meyers W. E. Long-acting delivery systems for peptides: inhibition of rat prostate tumors by controlled release of [D-Trp6]luteinizing hormone-releasing hormone from injectable microcapsules. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5845–5848. doi: 10.1073/pnas.81.18.5845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Reichlin M., Schnure J. J., Vance V. K. Induction of antibodies to porcine ACTH in rabbits with nonsteroidogenic polymers of BSA and ACTH. Proc Soc Exp Biol Med. 1968 Jun;128(2):347–350. doi: 10.3181/00379727-128-33011. [DOI] [PubMed] [Google Scholar]
  12. Schally A. V., Redding T. W. Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7275–7279. doi: 10.1073/pnas.84.20.7275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Thomas C. M., van den Berg R. J., Segers M. F. Measurement of serum estradiol: comparison of three "direct" radioimmunoassays and effects of organic solvent extraction. Clin Chem. 1987 Oct;33(10):1946–1947. [PubMed] [Google Scholar]
  14. Veber D. F., Freidlinger R. M., Perlow D. S., Paleveda W. J., Jr, Holly F. W., Strachan R. G., Nutt R. F., Arison B. H., Homnick C., Randall W. C. A potent cyclic hexapeptide analogue of somatostatin. Nature. 1981 Jul 2;292(5818):55–58. doi: 10.1038/292055a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES