Synthesis and evaluation of 68 Ga-HBED-CC-EDBE-folate for positron-emission tomography imaging of overexpressed folate receptors on CT26 tumor cells.

Abstract

The 68 Ga is a positron-emitting radionuclide that can be combined with bifunctional chelating agents and bioactive substances for use as positron-emission tomography (PET) diagnostic agents. The HBED-CC is an acyclic chelating agent that is rapidly labeled with 68 Ga under mild conditions. To target cancer cells, bioactive substances can be conjugated to the carboxyl terminus of HBED-CC. Because folic acid strongly binds to folate receptors that are overexpressed on the surfaces of many types of cancer cells, it was coupled with HBED-CC through a small polyethylene glycol-based linker (EDBE) to generate an active, receptor-selective targeting system. The HBED-CC-EDBE-folate (HCEF) precursor was readily labeled with 68 Ga in 5 minutes at room temperature (98% radiochemical yield; 99% radiochemical purity after isolation). In cellular uptake tests, higher uptakes of 68 Ga-HCEF were observed for the CT26 and KB cell lines (which express folate receptors) than for the A549 cell line (which does not). Finally, in vivo micro-PET measurements over 2 hours of binding in BALB/c mice into which CT26 tumors had been transplanted showed the selective accumulation of 68 Ga-HCEF in the folate receptor-expressing CT26 tumors. These results confirmed the potential of 68 Ga-HCEF as a PET diagnostic agent for tumors that express folate receptors.

• Authors: Pyeong Seok Choi, Jun Young Lee, Jeong Hoon Park, Sang Wook Kim
• Journal: Journal of labelled compounds & radiopharmaceuticals (J Labelled Comp Radiopharm) Vol. 61 Issue 1 Pg. 4-10 (01 2018) ISSN: 1099-1344 [Electronic] England
• PMID: 28901564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 John Wiley & Sons, Ltd.

Chemical References

• Gallium Radioisotopes
• Radiopharmaceuticals
• N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid
• Polyethylene Glycols
• Folic Acid
• Edetic Acid

Topics

• Animals
• Cell Line, Tumor
• Edetic Acid (analogs & derivatives, chemistry)
• Folic Acid (analogs & derivatives)
• Gallium Radioisotopes (chemistry)
• Humans
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental (diagnostic imaging)
• Polyethylene Glycols (chemistry)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics)
• Tissue Distribution