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Study on biodistribution and radioimmunoimaging of (131)iodine-labeled monoclonal antibody D-D3 against progastrin-releasing peptide31-98 in tumor-bearing mouse.

Abstract
This study was aimed at investigating the biodistribution and radioimmunoimaging of (131)I-D-D3 in nude mice bearing different types of tumor xenografts. Radioiodination of the D-D3 antibody was performed with the chloramine-T method. The radiochemical purity was determined through thin-layer chromotography. (131)I-D-D3 was injected into healthy Kunming mice via a tail vein, and the %ID/g for various organs was obtained. Similarly, the %ID/g and tumor/nontumor tissue ratio of (131)I-D-D3 in nude mice bearing small cell lung cancer (SCLC) xenografts were obtained. Planar images of (131)I-D-D3 in tumor-bearing nude mice were acquired at different times after injection. The (131)I-D-D3 labeling rate was 86.56%  ± 3.8%. The radiochemical purity of (131)I-D-D3 was 99.27%  ± 0.6%. After 12 hours of incubation in 37°C water bath, the radiochemical purity was 97.64%  ±  0.5% and remained at 88.38% ± 0.4% after 48 hours. After being mixed with healthy human serum for 24 hours, the radiochemical purity was more than 64%. The metabolism of (131)I-D-D3 in healthy Kunming mice was consistent with a two-compartment model with first-order absorption; T(1/2α) and T(1/2β) were 0.25 and 37.89 hours, respectively. The %ID/g of (131)I-D-D3 in SCLC xenografts was much higher than those of other tissues at 48 hours after injection, and the tumor/nontumor tissue ratio also gradually increased with time. After 24 hours of injection, planar imaging was obtained, which clearly showed a contrasting tumor on the right armpit of nude mice bearing SCLC with high concentrations of radioactivity. Also, nude mice bearing gastric cancer showed similar results as that of the SCLC with a lower radioactivity level. No observable accumulation was observed in nude mice bearing pancreatic cancer or lung adenocarcinoma. The labeling rate and radiochemical purity of (131)I-D-D3 were high and stable. (131)I-D-D3 selectively accumulated at tumors that highly expressed progastrin-releasing peptide; therefore, it is a promising radioimmunoimaging reagent for SCLC.
AuthorsZengli Liu, Xiaolin Zhou, Yizhen Shi, Shouying Du, Yi Yang, Jun Tang, Yongmei Shen
JournalCancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 26 Issue 2 Pg. 229-35 (Apr 2011) ISSN: 1557-8852 [Electronic] United States
PMID21510749 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Immunoconjugates
  • Iodine Radioisotopes
  • Peptide Fragments
  • Recombinant Proteins
  • pro-gastrin-releasing peptide (31-98)
Topics
  • Animals
  • Antibodies, Monoclonal (immunology, pharmacokinetics)
  • Humans
  • Immunoconjugates (immunology, pharmacokinetics)
  • Iodine Radioisotopes (pharmacokinetics)
  • Isotope Labeling (methods)
  • Lung Neoplasms (immunology, metabolism, radionuclide imaging)
  • Mice
  • Mice, Nude
  • Peptide Fragments (immunology, pharmacokinetics)
  • Radioimmunodetection
  • Recombinant Proteins (immunology, pharmacokinetics)
  • Small Cell Lung Carcinoma (immunology, metabolism, radionuclide imaging)
  • Tissue Distribution
  • Transplantation, Heterologous

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