Abstract | PURPOSE: 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. METHODS: 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. RESULTS: [(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. CONCLUSION: 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.
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Authors | Lucia Martiniova, Susannah Cleary, Edwin W Lai, Dale O Kiesewetter, Jurgen Seidel, Linda F Dawson, Jacqueline K Phillips, David Thomasson, Xiaoyuan Chen, Graeme Eisenhofer, James F Powers, Richard Kvetnansky, Karel Pacak |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 39
Issue 2
Pg. 215-26
(Feb 2012)
ISSN: 1872-9614 [Electronic] United States |
PMID | 21958851
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- Contrast Media
- Norepinephrine Plasma Membrane Transport Proteins
- Vesicular Monoamine Transport Proteins
- fluorodopa F 18
- 6-fluorodopamine
- Dihydroxyphenylalanine
- Dopamine
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Topics |
- Adrenal Gland Neoplasms
(diagnosis, diagnostic imaging)
- Animals
- Contrast Media
(pharmacokinetics)
- Dihydroxyphenylalanine
(analogs & derivatives, pharmacokinetics)
- Dopamine
(analogs & derivatives, pharmacokinetics)
- Female
- Liver Neoplasms
(diagnosis, secondary)
- Lung Neoplasms
(diagnosis, secondary)
- Magnetic Resonance Imaging
(methods)
- Mice
- Neoplasm Recurrence, Local
(diagnosis, secondary)
- Neoplasms, Experimental
(diagnosis, secondary)
- Norepinephrine Plasma Membrane Transport Proteins
(metabolism)
- Ovarian Neoplasms
(diagnosis, secondary)
- Pheochromocytoma
(diagnosis, diagnostic imaging, secondary)
- Positron-Emission Tomography
(methods)
- Sensitivity and Specificity
- Tomography, X-Ray Computed
(methods)
- Vesicular Monoamine Transport Proteins
(metabolism)
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