Longitudinal microSPECt/CT imaging and pharmacokinetics of synthetic luteinizing hormone-releasing hormone (LHRH) vaccine in rats

Anticancer Res. 2007 Sep-Oct;27(5A):3251-8.

Abstract

Background: Luteinizing hormone-releasing hormone (LHRH)-derived decapeptide-based vaccines have been used in studies of immunocastration and immunotherapy of prostate cancer, but no image data are available on the kinetics of vaccines post injection (p.i.). Therefore, an 131I radiolabeled LHRH-derived immunogen was developed to visualize and evaluate the retention of LHRH-derived vaccines in rats.

Materials and methods: The LHRH immunogens, which contained equal moles of 131I-p607E, p667 and p500, were formulated with an equal volume of an adjuvant, Montanide ISA50. MicroSPECT/CT imaging was performed to visualize the retention of the radiolabeled immunogen up to 30 days after intramuscular inoculation of 25 microg immunogens. The pharmacokinetics, distribution and excretion were also evaluated.

Results: The radiochemical purity of 131I-p607E was 97.85+/-2.12%. The longitudinal microSPECT/CT imaging revealed that most 131I-p607E was retained at the injected muscle site until 30 days p.i.. Biodistribution showed that 34.56+/-4.27% of radioactivity remained at the injected muscle site at 28 days p.i.. The cumulative radioactivity excreted via urine was 30.02+/-3.82% up to day 28 p.i.. The elimination half-life (t1/2), Tmax and Cmax were 158.67 h, 24 h, and 0.026 percentage of injected dose per gram (%ID/g), respectively.

Conclusion: The LHRH immunogen, 131I-p607E, was mainly retained at the intramuscular injection site during the whole study period. The microSPECTICT imaging modality can be used to monitor the location and distribution of the LHRH immunogen, 131I-p607E, in a rat model.

MeSH terms

  • Animals
  • Cancer Vaccines / pharmacokinetics*
  • Epitopes, T-Lymphocyte / immunology
  • Gonadotropin-Releasing Hormone / immunology*
  • Iodine Radioisotopes
  • Isotope Labeling
  • Longitudinal Studies
  • Male
  • Prostatic Neoplasms / therapy
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods
  • Vaccines, Synthetic / metabolism

Substances

  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Iodine Radioisotopes
  • Vaccines, Synthetic
  • Gonadotropin-Releasing Hormone