Comparative biodistribution of indium- and yttrium-labeled B3 monoclonal antibody conjugated to either 2-(p-SCN-Bz)-6-methyl-DTPA (1 B4M-DTPA) or 2-(p-SCN-Bz)-1,4,7,10-tetraazacyclododecane tetraacetic acid (2B-DOTA)

Abstract

The biodistribution of indium-111/yttrium-88-labeled B3 monoclonal antibody, a murine IgG1k, was evaluated in non-tumor-bearing mice. B3 was conjugated to either 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M) or 2-(p-SCN-Bz)-1,4,7,10 tetraazacyclododecane tetra-acetic acid (2B-DOTA) and labeled with 111In at 1.4-2.4 mCi/mg and 88Y at 0.1-0.3 mCi/mg. Non-tumor-bearing nude mice were co-injected i.v. with 5-10 microCi/4-10 micrograms of 111In/88Y-labeled B3 conjugates and sacrificed at 6 h and daily up to 168 h post-injection. Mice injected with 111In/88Y-(1B4M)-B3 showed a similar biodistribution of the two radiolabels in all tissues except the bones, where significantly higher accretion of 88Y than 111In was observed, with 2.8% +/- 0.2% vs 1.3% +/- 0.16% ID/g in the femur at 168 h, respectively (P < 0.0001). In contrast, mice receiving the 111In/88Y-(DOTA)-B3 conjugate showed significantly higher accumulation of 111In than 88Y in most tissues, including the bones, with 2.0% +/- 0.1% vs 1.2% +/- 0.09% ID/g in the femur at 168 h, respectively (P < 0.0001). Whereas the ratios of the areas underneath the curve (%ID x h/g) in the blood, liver, kidney and bone were 0.96, 1.12, 1.13, and 0.74 for 111In/88Y-(1B4M)-B3 and 0.84, 1.23, 1.56, and 1.31 for 111In/88Y-(DOTA)-B3, respectively, ratios approximately 1 were observed between 111In-(1B4M)-B3 and 88Y-(DOTA)-B3. In summary, while neither 1B4M nor DOTA was equally stable for 111In and 88Y, the fate of 88Y-(DOTA)-B3 could be closely traced by that of 111In-(1B4M)-B3.

Pulsed High-Intensity Focused Ultrasound Enhances Uptake of Radiolabeled Monoclonal Antibody to Human Epidermoid Tumor in Nude Mice

“…The biodistribution of 111 In-MX-B3 in mice with pulsed-HIFU-exposed tumors was similar to that reported previously for mice without pulsed-HIFU exposure (24,25); the uptake in blood, lung, and bone was almost identical in these studies. However, uptake in other organs, such as liver, spleen, and kidney, was slightly higher in this study, perhaps because the 111 In-MX-B3 prepared for this study contained a small fraction (7%) of a dimeric or higher molecular form of B3 that was taken up by reticular endothelial cells in the liver and spleen or catabolized into smaller antibody fragments that were then taken up by the kidneys, thereby resulting in a slight increased uptake in these organs.…”

“…The purpose of the current study was to investigate if pulsed-HIFU exposures could enhance the delivery of an mAb, 111 In-MX-B3, to a solid human epidermoid tumor in a murine model. The tumor uptake and retention of 111 In-MX-B3 in the control tumors not receiving the pulsed-HIFU exposure was similar to that reported previously (24,25). In contrast, the pulsed-HIFU exposure increased the tumor peak uptake value (37.55 6 16.37 vs. 24.99 6 2.40 %ID/g for control tumor) and shortened the peak tumor uptake time (24 vs. 48 h) compared with the control tumor.…”

“…Timeactivity curves for 111 In-MX-B3 were generated from the mean %ID/g in both tumors. The area under the curve (AUC) (%ID · h/g) was then calculated using a trapezoid integration from 1 to 120 h (25).…”

“…This epitope is abundantly and uniformly expressed by most carcinomas (23). In preclinical studies, tumor targeting of radiolabeled B3 was investigated in nude mice xenografted with A431, a human epidermoid carcinoma cell line expressing the Lewis y (24,25). Biodistribution of 111 In/ 88 Y-radiolabeled B3 antibody has shown good tumor localization in A431 tumor-bearing nude mice (24,25).…”

Pretargeted α Emitting Radioimmunotherapy Using 213Bi 1,4,7,10-Tetraazacyclododecane-N,N′,N″,N‴-Tetraacetic Acid-Biotin

“…We have shown previously that B3, an anti-Le y murine IgG1 monoclonal antibody, can efficiently target A431 tumor xenografts in nude mice (27). This work led to a Phase I therapy trial with 111 In and 90 Y B3 in patients with a variety of tumor types bearing the target antigen.…”