Comparative biodistribution of indium- and yttrium-labeled B3 monoclonal antibody conjugated to either 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M-DTPA) or 2-(p-SCN-Bz)-1,4,7,10-tetraazacyclododecane tetraacetic acid (2B-DOTA).
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.
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Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.
Kinuya
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Garmestani
K
K
Brechbiel
M W
MW
Wu
C
C
Pai
L H
LH
McMurry
T J
TJ
Gansow
O A
OA
Pastan
I
I
Paik
C H
CH
D000818:Animals; D002614:Chelating Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D017879:Isothiocyanates / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
C087160:2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid; D002614:Chelating Agents; D006571:Heterocyclic Compounds; D007205:Indium Radioisotopes; D017879:Isothiocyanates; D015021:Yttrium Radioisotopes; C077295:2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid; D004369:Pentetic Acid