Intratumoral distribution of two consecutive injections of chimeric antibody G250 in primary XXXX : implications for fractionated dose radioimmunotherapy.

@entity1 @entity1358 @entity5
Tumor uptake of the chimeric G250 (cG250) monoclonal antibody (mAb) in @entity1 with primary @entity1358 ( @entity1358 ) is among the highest reported in solid @entity5 . However, as observed in other @entity5 types, the intratumoral distribution of the antibody is highly heterogeneous, which may limit the efficacy of radioimmunotherapy. A number of highly dynamic physiological factors have been postulated that may contribute to heterogeneous @entity5 uptake of antibodies. Their impact on @entity5 uptake of antibodies may vary from one @entity5 region to another as well as from one day to the next. Here, we report on a clinical study that was designed to investigate whether the pattern of mAb cG250 uptake within @entity1358 is altered with subsequent injections. Ten @entity1 with a clinical diagnosis of primary @entity1358 were studied. Nine days before surgery, @entity1 received 125I-cG250 (5 mg of cG250, 50 microCi of 125I), followed by a second injection of 131I-cG250 (5 mg of cG250, 3.5 mCi of 131I) 4 days later. Postsurgery, the @entity5 was cut into (1-cm) thick slices. Slices were imaged on a gamma camera, and the slice with the most pronounced heterogeneity in 131I-cG250 distribution was selected and cut into 1-cm3 cubes. Each cube was analyzed for 121I-cG250 and 131I-cG250 uptake, and the 131I/125I ratio was determined. For each @entity5 slice, the distribution patterns of both isotopes were reconstructed and compared with each other. All @entity5 analyzed showed a heterogeneous distribution of both isotopes throughout the @entity5 slice; focal uptake in some areas of a @entity5 reached very high levels (up to 0.19% injected dose/g), whereas other tumorous areas of the same slice showed much lower uptake (as low as 0.0047% injected dose/g). Remarkably, in all @entity5 , the distribution pattern of both injections was identical: without exception, in all samples analyzed (n = 692), the uptake of 125I-cG250 was similar to 131I-cG250 uptake. Overall, the 131I/125I ratio was 1.64+/-0.31 (mean+/-SD). The constant 131I/125I ratios, observed in all @entity5 samples investigated, indicate that the @entity5 parameters governing cG250 mAb uptake were not altered significantly within the time period studied. In addition, the results of this study suggest that multiple radiolabeled antibody injections, administered within short time periods, will target the same areas within a @entity5 and, thus, will not solve the problem of heterogeneous @entity5 uptake of antibody.
