Antibody-dependent difference in biodistribution of monoclonal antibodies in animal models and humans

 The study was designed to clarify the difference in pharmacokinetics of monoclonal antibodies (mAb) in animal models and humans, and to elucidate the applicability of animal models. ^99mTc-labeled murine mAb – against carcinoembryonic antigen (designated BW431/26), and neural cell adhesion molecule (NE150) – and one chimeric mouse/human mAb against nonspecific cross-reacting antigen (chNCA) were administered i.v. to normal mice and athymic mice (370 kBq, 400 ng) xenografted with human cancer cells expressing antigens, and into patients with tumor (925 MBq, 1 mg). The biodistribution of two of the three mAb (not ^99mTc-BW431/26) differed clearly in mice and patients. ^99mTc-NE150 showed specific uptake in xenografted tumor and otherwise a normal biodistribution; however, clinical examination showed increased uptake in the liver with rapid blood clearance (mean α half-life = 31.1 min) compared with ^99mTc-BW431/26 (28.4 h). ^99mTc-chNCA demonstrated increased blood clearance and renal excretion in both normal and athymic mice, with accumulation in tumors. Clinical examination showed rapid blood clearance (mean α half-life = 6.4 min) and increased uptake in the liver. High-performance liquid chromatographic analysis of ^99mTc-chNCA revealed the immune complex in blood, suggesting uptake of the complex by the reticuloendothelial cells. The biodistribution of radiolabeled mAb in animal and human models was variable and specific for each of the three mAb. The results of animal studies with mAb should be evaluated carefully before being extrapolated to humans, on the basis of the nature of the mAb and interacting substances. Received: 9 April 1997 / Accepted 3 March 1998     

Effects of the Over-Expression of the rolC Gene on Leaf Development in Transgenic Periclinal Chimeric Plants

Using Agrobacterium tumefaciens harboring a vector that carriedthe rolC gene under the control of the 35S RNA promoter of cauliflowermosaic virus, we produced several transgenic plants. Two ofthem were periclinal chimeras with altered leaves that had wrinkleddark green margins and inner pale green regions. One chimericplant had shortened internodes, reduced apical dominance, smallflowers and exhibited male sterility, but the other had a normalphenotype. Analysis of proteins, RNA and DNA indicated thatthe inner pale green tissues consisted of transformed cellswhile the outer dark green tissues were composed of non-transformedcells. Histological analysis indicated that mesophyll cellswere distorted and larger intercellular spaces were presentin the transformed pale green regions. Furthermore, in youngleaves, transformed mesophyll cells were larger than non-transformedcells. However, the normal parts had larger numbers of cellsper unit area than the transformed parts. These observationssuggest that ths expression of 35S-rolC in leaves caused inhibitionof cell division in developing leaves and that the undulatingmargins, composed of non-transformed cells, were a consequenceof the requirement for accommodating more cells in less spacewithin the region of rolC-transformed cells. (Received January 29, 1993; Accepted May 17, 1993)