Intratumoral distribution of two consecutive injections of chimeric antibody G250 in primary renal cell carcinoma: Implications for fractionated doseradioimmunotherapy

Tumor uptake of the chimeric G250 (cG250) monoclonal antibody (mAb) in pati ents with primary renal cell carcinoma (RCC) is among the highest reported in solid tumors. However, as observed in other tumor types, the intratumora l distribution of the antibody is highly heterogeneous, which may limit the efficacy of radioimmunotherapy. A number of highly dynamic physiological f actors have been postulated that may contribute to heterogeneous tumor upta ke of antibodies. Their impact on tumor uptake of antibodies may vary from one tumor region to another as well as from one day to the next. Here, we r eport on a clinical study that was designed to investigate whether the patt ern of mAb cG250 uptake within RCC tumors is altered with subsequent inject ions. Ten patients with a clinical diagnosis of primary RCC were studied. Nine da ys before surgery, patients received I-125-cG250 (5 mg of cG250, 50 mu Ci o f I-125), followed by a second injection of I-125-cG250 (5 mg of cG250, 35 mCi of I-131) 4 days later. Postsurgery, the tumor was cut into (1-cm) thic k slices. Slices were imaged on a gamma camera, and the slice with the most pronounced heterogeneity in I-131-cG250 distribution was selected and cut into 1-cm(3) cubes. Each cube was analyzed for I-125-cG250 and I-131-cG250 uptake, and the I-131/I-125 ratio was determined, For each tumor slice, the distribution patterns of both isotopes were reconstructed and compared wit h each other. All tumors analyzed showed a heterogeneous distribution of both isotopes th roughout the tumor slice; focal uptake in some areas of a tumor reached ver y high levels (up to 0.19% injected dose/g), whereas other tumorous areas o f the same slice showed much lower uptake (as low as 0.0047% injected dose/ g). Remarkably, in all tumors, the distribution pattern of both injections was identical: without exception, in all samples analyzed (n = 692), the up take of I-125-cG250 was similar to I-131-cG250 uptake. Overall, the I-131/I -125 ratio was 1.63 +/- 0.31 (mean +/- SD). The constant I-131/I-125 ratios, observed in all tumor samples investigated , indicate that the tumor parameters governing cG250 mAb uptake were not al tered significantly within the time period studied. In addition, the result s of this study suggest that multiple radiolabeled antibody injections, adm inistered within short time periods, will target the same areas within a tu mor and, thus, will not solve the problem of heterogeneous tumor uptake of antibody.