Radioimmunoassay for Octapeptide Analogs of Somatostatin: Measurement of Serum Levels after Administration of Long-Acting Microcapsule Formulations

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-08, Vol.85 (15), p.5688-5692
• Main Authors: Mason-Garcia, Meredith, Vaccarella, Myra, Horvath, Judit, Redding, Tommie W., Groot, Kate, Orsolini, Piero, Schally, Andrew V.
• Format: Article
• Language: English
• Subjects: 550601 - Medicine- Unsealed Radionuclides in Diagnostics; ACCURACY; ANIMALS; ANTIBODIES; Antigens; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - blood; Antiserum; BETA DECAY RADIOISOTOPES; BIOASSAY; Biological and medical sciences; BLOOD SERUM; Capsules; CHEMICAL REACTIONS; Cross Reactions; DAYS LIVING RADIOISOTOPES; Delayed-Action Preparations; DIAGNOSTIC TECHNIQUES; DISEASES; ELECTRON CAPTURE RADIOISOTOPES; ENDOCRINE DISEASES; General pharmacology; HALOGENATION; Hormones; IMMUNOASSAY; IMMUNOLOGY; IMMUNOTHERAPY; Injections, Intramuscular; INTERMEDIATE MASS NUCLEI; IODINATION; IODINE 125; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; Male; MAMMALS; Medical sciences; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; PEPTIDES; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphates; POLYPEPTIDES; Predictive Value of Tests; PROTEINS; RABBITS; RADIOASSAY; RADIOIMMUNOASSAY; RADIOIMMUNODETECTION; RADIOIMMUNOLOGY; RADIOISOTOPES; RADIOLOGY AND NUCLEAR MEDICINE; RATS; Rats, Inbred Strains; RODENTS; Serum albumins; Sodium; Somatomedins; SOMATOSTATIN; Somatostatin - administration & dosage; Somatostatin - analogs & derivatives; Somatostatin - blood; THERAPY; TRACER TECHNIQUES; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.15.5688

The development of a long-acting delivery system for D-Phe-C$\overline{\text{ys-Tyr-D-Trp-Lys-Val-Cy}}$s-Trp-NH$_{2}$ (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.