Radio-labeled ERIC1: Relationship of biodistribution to the labeling nuclide and linker in neuroblastoma-bearing mice

1444 Objectives: Preliminary investigations of this team with I-131 ERIC1, a radioactively-labeled antibody to NCAM (the Neural Cell Adhesion Molecule) showed a high accumulation in tumor tissue (up to 60% ID/g) in neuroblastoma-xenograft-bearing SCID mice. Since Y-90 is a proven and clinically established therapeutic radionuclide but emits no gamma radiation, we will begin with biokinetic studies after labeling with the gamma emitter In-111, which is chemically very similar to Y. We will also test whether variation of the linker (DOTA or DTPA) influences the biokinetics. Methods: Labeling with I-131 or In-111 via the corresponding linker was carried out by standard procedures. The various radioimmuno-conjugates (RICs) were injected intravenously into neuroblastoma-bearing SCID mice. The biodistribution was measured at 24 h and 72 h post injection (p.i.) by collection and dissection of the blood, urine, liver, kidney, spleen, lung, gastrointestinal tract, femur, muscle, thyroid and tumor, and measurement of radioactivity using a well counter. The results were recorded as percentages of the applied dose per gm organ weight. Results: Accumulation of ERIC1 in the tumor was surprisingly high at a mean of about 30% ID/g (72 h p.i.). Similar levels of accumulation in tumors were found with the two In-111 labeled RICs. However, with the latter, 15-20% accumulation was found in liver, kidney and spleen while these values were markedly lower (