Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
권호 표지
DOI QR코드

DOI QR Code

Direct radio-iodination of folic acid for targeting folate receptor-positive tumors

  • Huynh, Phuong Tu (Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University) ;
  • Lee, Woonghee (Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University) ;
  • Ha, Yeong Su (Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University) ;
  • Yoo, Jeongsoo (Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University)
  • Received : 2018.06.08
  • Accepted : 2018.06.28
  • Published : 2018.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The folate receptor (FR) is a promising cell membrane-associated target for nuclear imaging of various cancers (via imaging $FR-{\alpha}$) and potentially also inflammatory diseases (via imaging $FR-{\beta}$), through the use of folic acid-based radioconjugates. However, there have been several drawbacks of previously reported radioconjugates, such as a short half-life of the radiolabel ($^{68}Ga\;t_{1/2}$ 68 min), a complex and time-consuming multistep radiosynthesis, and a high renal uptake of radiolabeled folate derivatives. The goal of this study was to develop an imaging probe by directly labeling folate with radioactive iodine without using an extra prosthetic group. The radiolabeling of folate was optimized using various labeling conditions and the labeled tracers were isolated by high-performance liquid chromatography. The in vitro stability of labeled folate was checked in phosphate-buffered saline and serum. The tumor-targeting efficacy of the probe was also evaluated by biodistribution studies using a murine 4T1 tumor model.

Keywords

References

  1. Gazzali AM, Lobry M, Colombeau L, Acherar S, Azais H, Mordon S, Arnoux P, Baros F, Vanderesse R, Frochot C. Stability of folic acid under several parameters. Eur J Pharm Sci 2016; 93:419-430. https://doi.org/10.1016/j.ejps.2016.08.045
  2. Low PS, Henne WA, Doorneweerd DD. Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res 2007; 41:120-129.
  3. Ke CY, Mathias CJ, Green MA. Folate-receptor-targeted radionuclide imaging agents. Adv Drug Deliv Rev 2004; 56:1143-1160. https://doi.org/10.1016/j.addr.2004.01.004
  4. Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem 2005; 338:284-293. https://doi.org/10.1016/j.ab.2004.12.026
  5. Xia W, Hilgenbrink AR, Matteson EL, Lockwood MB, Cheng JX, Low PS. A functional folate receptor is induced during macrophage activation and can be used to target drugs to activated macrophages. Blood 2009; 113:438-446.
  6. Vora A, Riga A, Dollimore D, Alexander KS. Thermal stability of folic acid. Thermochim Acta 2002; 392:209-220.
  7. Mathias CJ, Lewis MR, Reichert DE, Laforest R, Sharp TL, Lewis JS, Yang JF, Waters DJ, Snyder PW, Low PS. Preparation of $^{66}Ga-and\;^{68}Ga-labeled$ Ga (III)-deferoxamine-folate as potential folate-receptortargeted PET radiopharmaceuticals. Nucl Med Biol 2003; 30:725-731. https://doi.org/10.1016/S0969-8051(03)00080-5
  8. Ross TL, Honer M, Müller C, Groehn V, Schibli R, Ametamey SM. A New $^{18}F-Labeled$ Folic Acid Derivative with Improved Properties for the PET Imaging of Folate Receptor-Positive Tumors. J Nucl Med 2010; 51:1756-1762. https://doi.org/10.2967/jnumed.110.079756
  9. Siegel BA, Dehdashti F, Mutch DG, Podoloff DA, Wendt R, Sutton GP, Burt RW, Ellis PR, Mathias CJ, Green MA. Evaluation of $^{111}In-DTPA-folate$ as a receptor-targeted diagnostic agent for ovarian cancer: initial clinical results. J Nucl Med 2003; 44:700-707.
  10. Reber J, Struthers H, Betzel T, Hohn A, Schibli R, Muller C. Radioiodinated folic acid conjugates: evaluation of a valuable concept to improve tumor-tobackground contrast. Mol Pharm 2012; 9:1213-1221. https://doi.org/10.1021/mp200511t
  11. Soroka N, Filatov M, Korolev V, Bagiyan G, Aplin K, Gridasov G. Absorption of iodofolic acids by the cells of malignant tumors. Russ J Bioorg Chem 2012; 38:734-44.
  12. Kulkarni P, Antich P, Constantinescu A, Prior J, Nguyen T, Fernando J, Anderson J, Weitman S, Kamen B, Parkey R. Folate receptor imaging with $^{125}I$ labeled folic acid with a whole body small animal imaging device built with plastic scintillating optical fibers. Nucl Instr Meth Phys Res B 1995; 99:800-803. https://doi.org/10.1016/0168-583X(95)00220-0