RADIOIMMUNOTHERAPY OF BREAST-CANCER XENOGRAFTS WITH MONOCLONAL-ANTIBODY ICR12 AGAINST C-ERBB2 P185 - COMPARISON OF IODOGEN AND N-SUCCINIMIDYL 4-METHYL-3-(TRI-N-BUTYLSTANNYL)BENZOATE RADIOIODINATION METHODS

C-erbB2 p185 is a proto-oncogene product expressed in 25-30% of human invasive breast cancers that is associated with poor prognosis and res istance to endocrine therapy and chemotherapy. It is minimally express ed in normal adult tissues (M, F, Press st at, Oncogene, 5: 953-962, 1 990). For this reason, it is an attractive target for radioimmunothera py and other antibody-directed therapies, ICR12 is a rat IgG2a monoclo nal antibody directed against a protein epitope of the external domain of the c-erbB2 p185, We performed experiments to optimize the direct iodination of ICR12 with I-131 using the IodoGen method, and we found impairment of immunoreactive fraction with increasing specific activit y, N-Succinimidyl 4-methyl-3-(tri-n-butylstannyl)benzoate (MATE) is a tin ester that can be radioiodinated easily and then coupled to the ep silon-amino group of lysine residues, This method has been shown to ha ve improved uptake in tumors compared with antibody labeled by direct iodination (P, K. Garg et al., Nucl, Med. Biol,, 20: 379-387, 1993), I CR12 could be labeled up to 16 mCi/mg by this technique without loss o f immunoreactive fraction, Whole-body retention of MATE-labeled ICR12 was less than IodoGen (P < 0.0001), Radioimmunotherapy experiments in athymic mice bearing established MDA MB 361 human breast cancer xenogr afts showed growth inhibition for >24 days at a dose of 600 mu Ci/mous e (P < 0.0001) when labeled by the IodoGen technique, and 12 days usin g the MATE method (P < 0.0001).