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

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