VARIABLES INFLUENCING TUMOR DOSIMETRY IN RADIOIMMUNOTHERAPY OF CEA-EXPRESSING CANCERS WITH ANTI-CEA AND ANTIMUCIN MONOCLONAL-ANTIBODIES

In this study, we examined the factors that may influence tumor dosime try in the radioimmunotherapy of solid, CEA-expressing cancers, Method s: Data from 119 tumors in 93 patients with CEA-expressing cancers wer e analyzed, The patients underwent radioimmunotherapy with the I-131-l abeled IgG(1) anti-CEA antibodies NP-4 (K-a = 10(8) M-1) or MN-14 (K-a = 10(9) M-1), its humanized form hMN-14, as well as the anticolon-spe cific antigen-p (CSAp) antibody, Mu-9. For dosimetry, the biodistribut ion, targeting kinetics and cumulated activity of tumors and organs we re determined from planar and SPECT imaging, Results: An inverse logar ithmic relationship between tumor size and antibody uptake was found f or both anti-CEA antibodies, whereas no such relationship was found fo r Mu-9. The absolute tumor. uptake was identified as the most importan t factor determining the radiation dose to the tumor (r = 0.9), with t he biological half-life of the antibody in the tumor being of secondar y importance (r = 0.5). No significant difference in tumor uptake was found between both anti-CEA antibodies, despite their tenfold differen ce 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 h alf-lives of the anti-CEA antibodies were significantly lower in color ectal than in ail other tumor types (p = 0.01). Conclusion: In radioim munotherapy, tumor uptake appears to be the most important dose-determ ining factor. Differences in antibody affinity are reflected by differ ences in the biological half-life, not the absolute uptake. Especially favorable conditions for anti-CEA antibodies seem to prevail in color ectal cancer patients having minimal disease, as well as in medullary thyroid cancer, where cytotoxic tumor doses might be expected. Antimuc in antibodies may have a particular advantage in the treatment of pati ents with larger colorectal tumors.