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In vitro and in vivo characterization of a new receptor specific indium‐111 labeled DOTA‐ST conjugate for targeting guanylin receptors in human colon cancer cells
Author(s) -
Gali H.,
Sieckman G. L.,
Hoffman T. J.,
Owen N. K.,
Chin D. T.,
Forte L. R.,
Volkert W. A.
Publication year - 2001
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.25804401241
Subject(s) - dota , conjugate , in vivo , chemistry , in vitro , receptor , colorectal cancer , pharmacology , pharmacokinetics , radioimmunotherapy , cancer , cancer research , microbiology and biotechnology , medicine , immunology , biochemistry , biology , antibody , monoclonal antibody , mathematical analysis , mathematics
A new DOTA‐6‐Ahx‐Phe 19 ‐ST[1–19] conjugate (DOTA‐Ahx‐ST), for specific targeting of guanylin receptors expressed on human colon cancer cells, was synthesized and radiolabeled with indium‐111. In vitro competitive binding assays, employing T‐84 human colon cancer cells, demonstrated an IC 50 value of 3.0 ± 0.7 nM for the In‐DOTA‐Ahx‐ST conjugate. In vivo pharmacokinetic studies of 111 In‐DOTA‐Ahx‐ST conjugate in T‐84 human colon cancer derived xenografts in SCID mice conducted at 1, 4, and 24 hrs p.i. revealed efficient clearance from the blood pool (0.31 ± 0.06 %ID/g, 1 hr p.i.) with excretion mainly through the renal pathway (92.7 ± 0.5 %ID, 1 hr p.i.). Initial tumor uptake of 1.34 ± 0.20 %ID/g at 1 hr p.i. was observed with 54% and 18% retention at 4 and 24 hrs p.i. respectively. These results suggest that this DOTA‐Ahx‐ST peptide conjugate or a similar analogue may have an application as a radiopharmaceutical in the detection and treatment of human colon cancer using an appropriate radioisotope.