Imaging of Melanoma Using ~(64)Cu- and ~(86)Y-DOTA-ReCCMSH(Arg~(11)),a Cyclized Peptide Analogue of alpha-MSH

摘要

Early detection of melanoma is essential,since a patient's prognosis with metastatic melanoma is poor.Previous studies showed that ~(111)In-DOTA-ReCCMSH(Arg~(11)),a cyclic analogue of alpha-melanocyte stimulating hormone (a-MSH),exhibited high tumor concentration and rapid clearance from nontarget tissue.The goal of this current study was to label DOTA-ReCCMSH-(Arg~(11)) with beta~+-emitting radionuclides,to determine if the high sensitivity of positron emission tomography (PET) imaging would aid in the detection of malignant melanoma.DOTA-ReCCMSH(Arg~(11)) was labeled with ~(64)Cu and ~(86)Y.Biodistribution and small animal PET imaging were carried out in mice implanted with B16/F1 murine melanoma tumor and compared with data obtained in the same animal model with [~(18)F]FDG.In both cases a subset of animals were co-injected with 20 mug of DOTA-ReCCMSH(Arg~(11)) to determine if tumor concentration was receptor mediated.Tumor concentration for both the ~(86)Y- and ~(64)Cu-complexes reached a maximum at 30 min,while coadministering 20 mug of unlabeled complex reduced tumor uptake significantly.Nontarget organ concentration was considerably lower with ~(86)Y-DOTA- ReCCMSH(Arg~(11)) than its ~(64)Cu analogue,except in the kidneys,where the ~(64)Cu complex had lower accumulation at all time points.Small animal PET images for both complexes showed the tumor could be visualized after 30 min,with the standardized uptake value (SUV) analysis following a similar trend as the biodistribution data.The data obtained suggests that DOTA-ReCCMSH(Arg~(11)),when labeled with beta~+-emitting radionuclides,has the potential for early detection of malignant melanoma by exploiting the sensitivity and high resolution of PET.