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

Purpose: To evaluate the usefulness of [F-18]-6-fluorodopamine ([F-18]-DA) and [F-18]-L-6-fluoro-3,4-dihydroxyphenylalanine ([F-18-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 I and 2 (VMAT1 and VMAT2), all important for [F-18]-DA and [F-18]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUVmax values were calculated from [F-18]-DA and [F-18]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [F-18]-DA detected less metastatic lesions compared to [F-18]-DOPA. TLR values for liver metastases were 2.26-2.71 for [F-18]-DOPA and 1.83-2.83 for [F-18]-DA. A limited uptake of [F-18]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [F-18]-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 [F-18]-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, [F-18]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [F-18]-DOPA had overall better sensitivity than [F-18]-DA for the detection of metastases. Subcutaneous tumors were localized only with [F-18]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [F-18]-DOPA provides better visualization of lesions than [F-18]-DA. (C) 2012 Elsevier Inc. All rights reserved.