64Cu (t1/2 = 12.7 h, Emaxb+ = 656 keV; Emaxb- = 573 keV; Emaxg = 511 keV) is one of the most useful radionuclides for positron emission tomography (PET) imaging of cancers due to its ideal physical properties. Its half-life allows optimal biodistribution of antibody conjugates with slow clearance, and the low �+ maximal energy results in good intrinsic image resolution. Clinical and Preclinical evaluations of various 64Cu-labeled antibody conjugates as targeted PET agents have shown encouraging results. However, less progress has been made on development of bifuncitonal chelators of 64Cu. An effective chelator must be empolyed to minimize transchelation of 64Cu to the metal-binding proteins. We have synthesized new bifunctional chelators for PET applications using64Cu. The chelators were conjugated to a tumor-targeting moiety, trastuzumab, a bile acid, or transferrin. Trastuzumab targets HER2 receptor over-expressed in various cancer and was approved in the treatment of  metastatic breast cancer. Transferrin and bile acid are known to target transferrin receptor and bile acid transporter over-expressed in colon cancer. Amphiphilic bile acids including cholic acid (CA), deoxycholic acid (DCA),or chenodeoxycholic acid (CDCA) have been investigated as a shuttle for therapeutic and diagnostic drugs. The new bifunctional chelators were conjugated to the targeting moiety, trastuzumab, transferrin, or bile acid. The corresponding conjugates were evaluated for their radiolabeling efficiency with 64Cu. Comparative complex stability of the 64Cu-labeled conjugates in human serum was also evaluated. The conjugated chelators were rapid in binding to 64Cu, and radiolabeled conjugates displayed excellent in vitro stability. The result of the biological evaluation indicates that the new bifunctional chelators are promosing candidates for PET applications using 64Cu, and further biological evaluation of the conjugates using animals is warranted

Synthesis and biological evaluation of new bifunctional chelators for targeted positron emission tomography (PET) imaging using <sup>64</sup>Cu

246th National Meeting (2013)

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Synthesis and biological evaluation of new bifunctional chelators for targeted positron emission tomography (PET) imaging using 64Cu

Synthesis and biological evaluation of new bifunctional chelators for targeted positron emission tomography (PET) imaging using ⁶⁴Cu