Abstract | UNLABELLED: METHODS: The TF antigen-specific peptide IVWHRWYAWSPASRI was synthesized with the chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid ( NOTA) at the amino terminus, followed by a Gly-Ser-Gly (GSG) spacer. Amino acids Asp and Arg were introduced at both ends to enhance its solubility. Purified NO2A-GSG-DRD-IVWHRWYAWSPASRI-DRD (NO2A-TFpep) was radiolabeled with (64)Cu and evaluated for binding to human MDA-MB-435 breast cancer cells, 50% inhibitory concentration (IC(50)), and serum stability. In vivo pharmacokinetic and small-animal PET studies were performed using SCID mice bearing MDA-MB-435 tumor xenografts. RESULTS: (64)Cu-NO2A-TFpep bound to human MDA-MB-435 breast carcinoma cells, whereas almost no binding was observed to normal human breast 184A1 cells. The peptide exhibited an apparent IC(50) value of 70 ± 8.0 nM. In vivo biodistribution studies indicated radiolabeled peptide accumulation in tumors of MDA-MB-435 xenografted SCID mice of approximately 1.10 ± 0.20 percentage injected dose per gram (%ID/g) and 0.90 ± 0.12 %ID/g, at 0.5 and 1 h, respectively. Accumulation of radioactivity was low in other organs, with the exception of liver (1.52 ± 0.12 %ID/g) and kidneys (15.4 ± 1.73 %ID/g) at 1 h. Live imaging studies with (64)Cu-NO2A-TFpep (15 MBq) demonstrated good tumor uptake at 1 h after injection, whereas no tumor uptake was observed with a scrambled radiolabeled peptide (64)Cu-NO2A-GSG-DRD-RWSWWAVHRIPYSAI-DRD. CONCLUSION:
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Authors | Senthil R Kumar, Fabio A Gallazzi, Thomas P Quinn, Susan L Deutscher |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 52
Issue 11
Pg. 1819-26
(Nov 2011)
ISSN: 1535-5667 [Electronic] United States |
PMID | 21984800
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antigens, Tumor-Associated, Carbohydrate
- Copper Radioisotopes
- Peptide Fragments
- Thomsen-Friedenreich antigen
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Topics |
- Amino Acid Sequence
- Animals
- Antigens, Tumor-Associated, Carbohydrate
(chemistry, metabolism)
- Breast Neoplasms
(diagnostic imaging, metabolism, pathology)
- Cell Line, Tumor
- Cell Transformation, Neoplastic
- Copper Radioisotopes
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Isotope Labeling
- Mice
- Molecular Sequence Data
- Multimodal Imaging
- Peptide Fragments
(blood, chemistry, pharmacokinetics)
- Positron-Emission Tomography
(methods)
- Protein Stability
- Tomography, X-Ray Computed
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