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Improved intratumoral penetration of radiolabeled streptavidin in intraperitoneal tumors pretargeted with biotinylated antibody.

AbstractUNLABELLED:
Inefficient intratumoral penetration of pharmaceuticals is one of the major limiting factors against effective tumor-targeting therapy. This study investigated the effect of the distribution pattern of the binding site in tumors on the penetration of target material.
METHODS:
In the first experiment, radiolabeled biotinylated monoclonal antibody, MLS128, was injected intraperitoneally or intravenously into nude mice bearing intraperitoneal human colon cancer xenografts. In the second experiment, radiolabeled streptavidin was injected intraperitoneally in the tumor-bearing mice after the pretargeting with the unlabeled biotinylated antibody. Intratumoral distribution of radioactivity was examined with quantitative autoradiography.
RESULTS:
There was no difference in the biodistribution of biotinylated antibody between intraperitoneal and intravenous administrations, but autoradiography showed a higher uptake in the margin and a lower uptake in the center of radioactivity in tumor nodules with intraperitoneal injection and a more uniform intratumoral radioactivity distribution with intravenous injection. In the two-step method, radioactivity in a low dose of streptavidin with intraperitoneal pretargeting primarily localized at the tumor margin. By increasing the dose, streptavidin penetrated more deeply. In tumors with intravenous pretargeting, a more uniform intratumoral distribution of streptavidin was obtained. The biodistribution of radiolabeled streptavidin was the same between different pretargeting routes.
CONCLUSION:
The better intratumoral penetration of radiolabeled streptavidin after intravenous pretargeting than intraperitoneal pretargeting with biotinylated antibody may be the result of different intratumoral distribution of the binding site for the radiolabel.
AuthorsM Zhang, Z Yao, T Saga, H Sakahara, Y Nakamoto, N Sato, H Nakada, I Yamashina, J Konishi
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 39 Issue 1 Pg. 30-3 (Jan 1998) ISSN: 0161-5505 [Print] United States
PMID9443734 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Indicators and Reagents
  • Iodine Radioisotopes
  • Biotin
  • Streptavidin
Topics
  • Animals
  • Autoradiography
  • Biotin
  • Colonic Neoplasms (diagnostic imaging, radiotherapy)
  • Humans
  • Indicators and Reagents
  • Iodine Radioisotopes (pharmacokinetics)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Peritoneal Neoplasms (diagnostic imaging, radiotherapy)
  • Radioimmunodetection
  • Radioimmunotherapy
  • Streptavidin (pharmacokinetics)
  • Tissue Distribution

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