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Synthesis, Purification, and Tumor Cell Uptake of 67Ga-Deferoxamine−Folate, a Potential Radiopharmaceutical for Tumor Imaging
Abstract
The vitamin folic acid was covalently linked to the chelating agent deferoxamine (DF) via an amide bond using a simple carbodiimide coupling reaction. A mixture of two isomers, DF--folate(alpha) and DF--folate(gamma), was produced involving the alpha- and gamma-carboxyl group of folic acid, respectively. These two isomers were separated by anion-exchange chromatography using a NH4HCO3 gradient. Competitive binding studies revealed that only the DF-folate(gamma) is recognized by the folate receptor on KB cells, interacting with an affinity comparable to unconjugated folic acid. The DF--folate conjugates were radiolabeled with the gamma-emitting radionuclide 67Ga3+ and tested for uptake by cultured KB cells overexpressing the folate receptor. The cellular accumulation of 67Ga-DF-folate(gamma) tracer exhibited rapid uptake kinetics in cell culture with a t1/2 of approximately 3 min. The KB cell association of 67Ga-DF--folate(gamma) was competitively blocked by free folic acid, indicating that uptake of the 67Ga-DF--folate(gamma) was specifically mediated by the folate receptor. Since the folate receptor is overexpressed on the surfaces of many neoplastic cells, these results suggest that 67Ga-DF--folate(gamma) complex might be useful as a diagnostic agent for noninvasive imaging of folate receptor-positing tumors.
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Citations
Cited by
Leamon, C. (2004) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2004.01.008 · Cited by 558
Design of Folic Acid‐Conjugated Nanoparticles for Drug Targeting
Stella, B., Arpicco, S., Peracchia, M. T., Desmaële, D., Hoebeke, J., Renoir, M., D'Angelo, J., Cattel, L., & Couvreur, P. (2000) · Journal of Pharmaceutical Sciences · doi:10.1002/1520-6017(200011)89:11<1452::aid-jps8>3.0.co;2-p · Cited by 553
Radiometal-Labeled Agents (Non-Technetium) for Diagnostic Imaging
Anderson, C. J., & Welch, M. J. (1999) · Chemical Reviews · doi:10.1021/cr980451q · Cited by 455
Folate-targeted therapies for cancer
Xia, W., & Low, P. S. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100509v · Cited by 448
Self-citationYoo, H. S., & Park, T. G. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.08.017 · Cited by 444
Metadata
- Authors
- Wang, S., Lee, R. J., Mathias, C. J., Green, M. A., & Low, P. S.
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1996-01-01
- Volume
- 7
- Issue
- 1
- Pages
- 56-62
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W1986177211
- Cited by
- 245
- References
- 0
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Synthesis, Purification, and Tumor Cell Uptake of 67Ga-Deferoxamine−Folate, a Potential Radiopharmaceutical for Tumor Imaging. https://app.cochat.ai/papers/10.1021/bc9500709
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- Wang, S., Lee, R. J., Mathias, C. J., Green, M. A., & Low, P. S. (1996). Synthesis, Purification, and Tumor Cell Uptake of 67Ga-Deferoxamine−Folate, a Potential Radiopharmaceutical for Tumor Imaging. Bioconjugate Chemistry. https://doi.org/10.1021/bc9500709
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