Abstract | BACKGROUND: MATERIALS AND METHODS: A DOTA conjugated ST analogue DOTA-NCS-6-Ahx-Phe19-ST[1-19] ( DOTA-NCS-ST) was synthesized and labeled with indium-111. The non-radioactive indium analogue (In- DOTA-NCS-ST) was also prepared in macroscopic quantities. 111In-DOTA-NCS-ST was produced as a single species (>80% RCP) and purified by HPLC. Human colon cancer CaCO-2 and T-84 cells were used to evaluate the in vitro IC50 values for GC-C receptor binding and determine the cell uptake and retention of radioactivity. RESULTS: The DOTA-NCS-ST and In- DOTA-NCS-ST conjugates exhibit high in vitro binding affinity for GC-C receptors with IC50 values <10 nM. The in vitro cell binding studies with the 111In-DOTA-NCS-ST conjugate demonstrated that 111In-label ST internalizes in human colon cancer cells and exhibits long-term retention. CONCLUSION: The combination of radiolabeling efficacy and specific in vitro cell uptake and retention suggests that the DOTA-NCS-ST construct holds potential for the development of diagnostic or therapeutic radiopharmaceuticals labeled with trivalent radiometals for specific targeting of human colonic cancers.
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Authors | H Gali, G L Sieckman, T J Hoffman, G E Kiefer, D T Chin, L R Forte, W A Volkert |
Journal | Anticancer research
(Anticancer Res)
2001 Jul-Aug
Vol. 21
Issue 4A
Pg. 2785-92
ISSN: 0250-7005 [Print] Greece |
PMID | 11724355
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Bacterial Toxins
- Enterotoxins
- Escherichia coli Proteins
- Heterocyclic Compounds, 1-Ring
- In-DOTA-NSC-ST
- Indium Radioisotopes
- Radiopharmaceuticals
- Receptors, Cell Surface
- Receptors, Peptide
- heat stable toxin (E coli)
- Guanylate Cyclase
- Receptors, Enterotoxin
- Receptors, Guanylate Cyclase-Coupled
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Topics |
- Amino Acid Sequence
- Bacterial Toxins
(chemistry, metabolism)
- Colonic Neoplasms
(diagnostic imaging, metabolism)
- Enterotoxins
(chemistry, metabolism)
- Escherichia coli Proteins
- Guanylate Cyclase
- Heterocyclic Compounds, 1-Ring
(chemical synthesis, metabolism)
- Humans
- Indium Radioisotopes
(chemistry)
- Molecular Sequence Data
- Radionuclide Imaging
- Radiopharmaceuticals
(chemical synthesis, metabolism)
- Receptors, Cell Surface
(metabolism)
- Receptors, Enterotoxin
- Receptors, Guanylate Cyclase-Coupled
- Receptors, Peptide
- Substrate Specificity
- Tumor Cells, Cultured
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