Abstract: Cell surface receptors that are overexpressed in cancerous tumors are feasible molecular targets for cancer imaging. The transmembrane G-protein coupled receptor CXCR4 is overexpressed in tumors and has a crucial role in organ-specific metastasis of tumor cells. Cyclic pentapeptides such as FC131 and analogues have been developed to bind with high affinity and specificity to CXCR4. Unfortunately, when FC131 is radiolabelled and evaluated as a PET imaging agent, it demonstrates high retention in the liver and spleen due to its lipophilic character. Our group has previously exploited the sulfonation of tyrosine residues to improve peptide biodistribution by dramatically reducing lipophilicity while maintaining high affinity. Evaluation of sulfonated FC131 peptide analogues as PET imaging agents has been undertaken. In addition, modification of the naphthylalanine residue of FC131 has been investigated in order to reduce lipophilicity. The evaluation of FC131 cyclic peptide analogues conjugated to radionuclides such as ¹⁸F, ⁸⁶Ga, and ^212/213Bi, for the imaging and treatment of cancer, will be described.

Keywords: sulfonation, CXCR4, radiolabelled, PET, FC131, and imaging.