PMID: 9426693Jan 14, 1998Paper

Two-step radio-immunotargeting of renal-cell carcinoma xenografts in nude mice with anti-renal-cell-carcinoma X anti-DTPA bispecific monoclonal antibodies

International Journal of Cancer. Journal International Du Cancer
M H KranenborgEgbert Oosterwijk

Abstract

The specificity of antibodies offers unique opportunities to target tumors with radionuclides. However, due to the slow clearance of radiolabeled antibody, relatively high back-ground is observed in non-target organs. Pre-targeting protocols using bispecific monoclonal antibodies (bsMAbs) and radiolabeled chelates may overcome this problem. We have evaluated the anti-renal-cell-carcinoma (RCC) X anti-DTPA bsMAb G250 x DTIn1 for 2-step targeting of RCC tumors in nude mice. Tumor uptake of 111In-DTPA was similar up to a 3-day interval between bsMAb and 111In-DTPA injections and decreased thereafter. The effect of G250 x DTIn1 protein dose was studied. High tumor uptake was seen at 1 to 4 micrograms, whereas at higher doses uptake decreased. Tumor was saturated with 15 micrograms bsMAb. At the saturating bsMAb dose the 111In-DTPA amount was varied. High tumor uptake was observed at a 10-fold molar excess 111In-DTPA, whereas at higher excess uptake decreased. After priming with 15 micrograms bsMAb and targeting with a 10-fold molar excess 111In-DTPA, the biodistribution of 111In-DTPA was studied for 1 to 48 hr after injection. Good tumor retention of 111In-DTPA was observed, while the radiolabel cleared rapidly from the blood. Cons...Continue Reading

References

Feb 28, 1978·Biochemical and Biophysical Research Communications·P J Fraker, J C Speck
Oct 15, 1986·International Journal of Cancer. Journal International Du Cancer·E OosterwijkS O Warnaar
Dec 1, 1994·Scandinavian Journal of Clinical and Laboratory Investigation·K J Kairemo, K Liewendahl

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Citations

Apr 16, 2015·Frontiers in Pharmacology·Françoise Kraeber-BodéréJacques Barbet
Jun 13, 2000·Cancer Biotherapy & Radiopharmaceuticals·J BarbetJ F Chatal
Mar 31, 2000·Cancer Biotherapy & Radiopharmaceuticals·O C BoermanF H Corstens
Oct 6, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sally J DeNardoGerald L DeNardo
Dec 26, 2001·Chemical Reviews·C J Anderson, M J Welch
Oct 9, 2008·Bioconjugate Chemistry·Guozheng Liu, Donald J Hnatowich
Oct 11, 2003·Biotechnology Advances·D A Goodwin, C F Meares
Jun 11, 2008·Advanced Drug Delivery Reviews·Greg M ThurberK Dane Wittrup

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