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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).

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.
AuthorsL Camera, S Kinuya, K Garmestani, M W Brechbiel, C Wu, L H Pai, T J McMurry, O A Gansow, I Pastan, C H Paik
JournalEuropean journal of nuclear medicine (Eur J Nucl Med) Vol. 21 Issue 7 Pg. 640-6 (Jul 1994) ISSN: 0340-6997 [Print] GERMANY
PMID7957350 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid
  • Chelating Agents
  • Heterocyclic Compounds
  • Indium Radioisotopes
  • Isothiocyanates
  • Yttrium Radioisotopes
  • 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid
  • Pentetic Acid
Topics
  • Animals
  • Chelating Agents (pharmacokinetics, therapeutic use)
  • Female
  • Heterocyclic Compounds (pharmacokinetics, therapeutic use)
  • Indium Radioisotopes (therapeutic use)
  • Isothiocyanates (pharmacokinetics, therapeutic use)
  • Mice
  • Mice, Nude
  • Pentetic Acid (analogs & derivatives, pharmacokinetics, therapeutic use)
  • Radioimmunotherapy
  • Tissue Distribution
  • Yttrium Radioisotopes (therapeutic use)

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