Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to improve bifunctional chelate labelling of Mab, we investigated the use of a polyamino acid backbone for multiple DTPA substitutions. Poly-L-lysine (PL) (3.8 Kd, n = 25) was partially acetylated with MADTPA to yield 11 moles of DPTA per mole of PL. The average numbers of DTPA on PL were directly quantified with MADTPA-C-14. The remaining epsilon amino groups on PL-DTPA (I) were measured with TNBS reagent. A selective maleimide derivatization of (I) with S-SMPB yielded (II), which contains 2.3 moles of maleimide groups per mole of (I). The sulfhydryl activation of Mab-TP41.2F(ab')2 with 2-Iminothiolane hydrochloride produced (III), containing 1.3 moles of sulfhydryl groups per mole of Mab. Compounds (II) and (III) were combined to form a single thioether-spaced chain linkage of Mab-PL-DTPA (IV), which was subsequently chelated with 111In to yield (V), which was the compound of interest. Indium-111-PL-DTPA (VI) and 111In-DTPA-MabTP41.2F(ab')2 (VII) also were prepared for control studies. Direct cell binding assay revealed the mean immunoreactivity of (V) to be 79.4% and that of (VII) to be 39.5%. In a biodistribution study on melanoma tumor-bearing athymic mice at 4, 24, and 48 hr postinjection, the tumor/blood and tumor/liver ratios at 48 hr were 11.6 and 1.2 for (V), compared to 3.7 and 0.13, respectively, with (VII). Thus, the PL configuration for radiolabeled antibodies seems to result in decreased hepatic accumulation and retained tumor activity. The findings suggest that further studies of this new compound are warranted.
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PMID:Reduced hepatic accumulation of radiolabeled monoclonal antibodies with indium-111-thioether-poly-L-lysine-DTPA-monoclonal antibody-TP41.2F(ab')2. 155 42

Amino-dextran-10 (ADX-10) was partially oxidized to polyaldehyde-ADX which was then reacted with deferoxamine (DFO) to form a Schiff's base and converted into a secondary amine, ADX-DFO (I) with ten moles of DFO per mole of ADX. ADX-DFO was chelated with Indium or 111In to yield ten moles of In or 111In per mole of ADX-DFO. A selective maleimide derivatization of (I) with sulfosuccinimidyl-4-(p-maleimidophenyl) butyrate yielded (II), which contained 3 moles of maleimide groups per mole of (II). The sulfhydryl-amidinium derivatization of the monoclonal antibody (MoAb) TP41.2 with 2-IT produced (III). Compounds (II) and (III) were combined to form the thioether space-arm linkage of (IV), which was subsequently radiolabeled with 111In to yield (V). MoAb-DFO-111In, (VI), was also prepared for a control study. Direct cell binding revealed the immunoreactivity of (V) to be 79.7% and that of (VI) to be 60.3%. The in vitro stability of (V) at 4, 24, and 48 hours resulted in 1.7%, 7.0% and 16.0% hydrolysis respectively, as compared with 2.1%, 8.7% and 18.5% hydrolysis of the control (VI), at the same time intervals. In a biodistribution study in non-tumor rats at 4, 24, and 48 hours post-injection, the liver concentration at 48 hours was 2.97% (ID/g) for (V) and 4.84% (ID/g) for (VI). This novel technique for radiolabeling antibodies allows for a high level of radiometallic labeling, preservation of immunoreactivity, and reduction of uptake by the liver.
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PMID:Amino-dextran-deferoxamine: a potential polymeric heterobifunctional agent for high-level 111In-labeling of anti-melanoma monoclonal antibody TP41.2. 837 39