Variables influencing tumor dosimetry in radioimmunotherapy of CEA- expressing cancers with anti-CEA and antimucin monoclonal antibodies

Thomas M. Behr, Robert M. Sharkey, Malik E. Juweid, Robert M. Dunn, Zhiliang Ying, Cun H. Zhang, Jeffry A. Siegel, David M. Goldenberg

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53 Scopus citations

Abstract

In this study, we examined the factors that may influence tumor dosimetry in the radioimmunotherapy of solid, CEA-expressing cancers. Methods: Data from 119 tumors in 93 patients with CEA-expressing cancers were analyzed. The patients underwent radioimmunotherapy with the 131I-labeled IgG1 anti-CEA antibodies NP-4 (K(a) = 108 M-1) or MN-14 (K(a) = 109 M- 1), its humanized form hMN-14, as well as the anticolon-specific antigen-p (CSAp) antibody, Mu-9. For dosimetry, the biodistribution, targeting kinetics and cumulated activity of tumors and organs were determined from planar and SPECT imaging. Results: An inverse logarithmic relationship between tumor size and antibody uptake was found for both anti-CEA antibodies, whereas no such relationship was found for Mu-9. The absolute tumor uptake was identified as the most important factor determining the radiation dose to the tumor (r = 0.9), with the biological half-life of the antibody in the tumor being of secondary importance (r=0.5). No significant difference in tumor uptake was found between both anti-CEA antibodies, despite their tenfold difference in affinity. At comparable masses, colorectal and medullary thyroid cancers had significantly higher tumor uptakes (p = 0.02), as well as tumor-to-red marrow dose ratios, than other cancer types. The tumor half- lives of the anti-CEA antibodies were significantly lower in colorectal than in all other tumor types (p = 0.01). Conclusion: In radioimmunotherapy, tumor uptake appears to be the most important dose-determining factor. Differences in antibody affinity are reflected by differences in the biological half- life, not the absolute uptake. Especially favorable conditions for anti-CEA antibodies seem to prevail in colorectal cancer patients having minimal disease, as well as in medullary thyroid cancer, where cytotoxic tumor doses might be expected. Antimucin antibodies may have a particular advantage in the treatment of patients with larger colorectal tumors.

Original languageEnglish (US)
Pages (from-to)409-418
Number of pages10
JournalJournal of Nuclear Medicine
Volume38
Issue number3
StatePublished - Mar 1997

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Keywords

  • Carcinoembryonic antigen
  • Monoclonal antibodies
  • Radioimmunotherapy
  • Tumor dosimetry

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