Development of PET molecular targeting agents with gallium-68

Abstract

The utilization of positron emission tomography (PET) is increasing due to its superior imaging quality and its ability to be used for in vivo quantification. Radionuclides that decay by positron emission can be attached to the same chelators used for radiotherapy applications in diagnosis and staging. One such isotope is ⁶⁸Ga (T_1/2 = 68 min), which can be obtained from a long-lived generator by decay of the parent ⁶⁸Ge (T_1/2 = 270.8 d). The availability of ⁶⁸Ga from a generator plus its ability to be stably incorporated with a variety of chelates hold promise for expanding PET utilization to facilities unable to afford their own cyclotron. In collaboration with researchers at the University of Missouri, we have developed and evaluated peptides that target the melanocortin-1 receptor and the gastrin-releasing peptide (GRP) receptor for peptide guided imaging and the rapy. The melanocortin-1 receptor is an attractive target for peptide guided melanoma imaging and therapy. The limited number of receptors per cell, approximately 900–5000, requires high specific activity radiolabeled peptide ligands to prevent target saturation and ensure optimal cellular uptake. GRP receptors are over-expressed by a variety of human cancers such as breast, lung, pancreatic and prostate tumors, and due to bombesin's toxicity, it is necessary to label it in high specific activity. Results are presented on NOTA and DOTA bifunctionalized α-MSH and bombesin peptides, highlighting the differences in specific activity, preparation time and in vivo characteristics.