Radiolabeling of TETA- and CB-TE2A-conjugated peptides with copper-64

Abstract

The number of radiopharmaceuticals containing copper radionuclides for diagnostic imaging and targeted radiotherapy has grown considerably over the past few decades. This expansion has created the need for protocols allowing for the efficient chelation of 64Cu to peptide-chelator conjugates. Step 1A of this protocol describes a 64Cu-radiolabeling procedure for 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA)-conjugated peptides. This reaction is facile and requires the incubation of 64CuCl2 in 0.1 M ammonium acetate buffer with the TETA-peptide for 30 min at room temperature (20-23 °C). Step 1B of this protocol describes the radiolabeling procedure for 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CB-TE2A)-conjugated peptides. The CB-TE2A-peptide can be labeled with 64Cu in 0.1 M ammonium acetate buffer in 2 h at 95 °C. In both cases, the conjugates can be radiolabeled with 64Cu at greater than 95% purity and with specific activities of 37-111 MBq μg-1 (1-3 mCi μg-1). Both protocols are straightforward and can be completed within 3 h.