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

Martiniova, L., Cleary, S., Lai, E.W., Kiesewetter, D.O., Seidel, J., Dawson, L.F., Phillips, J.K., Thomasson, D., Chen, X., Eisenhofer, G., Powers, J.F., Kvetnansky, R. and Pacak, K. (2012) Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma. Nuclear Medicine and Biology, 39 (2). pp. 215-226.

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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.

Item Type: Journal Article
Murdoch Affiliation(s): School of Veterinary and Biomedical Sciences
Publisher: Elsevier BV
Copyright: © 2012 Elsevier Inc.
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