Instant Cu-62 labeling of the NOTA functionalized melanoma targeting peptide NOTA-ReCCMSH(Arg11)

Objectives The melanocortin-1 receptor is an attractive target for peptide guided melanoma imaging and therapy. However, the number of receptors per cell, approximately 900-5000, requires high specific activity radiolabeled peptide ligands to prevent target saturation and insure optimal cellular uptake. The ⁶²Zn/⁶²Cu(9.7 min) microgenerator routinely produces specific activity up to 200,000 Ci/mmol and is well along in FDA status with multiple kit based systems. The objective of this study was to investigate ⁶²Cu labeling of both NOTA and DOTA bifunctionalized versions of ReCCMSH(Arg11).

Methods Numerous metal radioisotopes have been applied for labeling of the bi-functionalized DOTA forms of ReCCMSH(Arg11). Labeling conditions are harsh, requiring lengthy time and HPLC purification. Reported specific activity for ⁶⁴Cu was only 600 Ci/mmol. In this study ⁶²Cu was used to label both NOTA and DOTA-ReCCMSH(Arg11) in acetate buffer, pH 4-6. Radiochemical labeling yield was measured by HPLC validated Oasis cartridge chromatography.

Results For NOTA form, >97% radiochemical yields were achieved instantly at room temperature at 1400 Ci/mmol. The DOTA form only achieved moderate labeling yield with longer times and heating.

Conclusions Functionalized NOTA ReCCMSH(Ag11) can be instantly labeled with ⁶²Cu and no post purification is required allowing immediate injection. ⁶²Cu can provide mouse imaging of peptides with small target molar levels and can also quickly satisfy regulatory requirements of human imaging with high injected activity up to 50 mCi.