Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

Abstract

To evaluate the usefulness of [(18)F]-6-fluorodopamine ([(18)F]-DA) and [(18)F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([(18)F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [(18)F]-DA and [(18)F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. SUV(max) values were calculated from [(18)F]-DA and [(18)F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. [(18)F]-DA detected less metastatic lesions compared to [(18)F]-DOPA. TLR values for liver metastases were 2.26-2.71 for [(18)F]-DOPA and 1.83-2.83 for [(18)F]-DA. A limited uptake of [(18)F]-DA was found in s.c. tumors (TLR = 0.22-0.27) compared to [(18)F]-DOPA (TLR = 1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [(18)F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [(18)F]-DOPA was found to utilize only VMAT2. MRI was superior in the detection of all organ tumors compared to microCT and PET. [(18)F]-DOPA had overall better sensitivity than [(18)F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [(18)F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [(18)F]-DOPA provides better visualization of lesions than [(18)F]-DA.