RT Journal Article SR Electronic T1 PET imaging of phosphodiesterase-4 identifies affected dysplastic bone in McCune-Albright syndrome, a genetic mosaic disorder JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.120.241976 DO 10.2967/jnumed.120.241976 A1 Lora Deuitch Weidner A1 Yuichi Wakabayashi A1 Louise A Stolz A1 Michael T Collins A1 Lori Guthrie A1 Milalynn Victorino A1 Joyce Chung A1 William Miller A1 Sami S Zoghbi A1 Victor W. Pike A1 Masahiro Fujita A1 Robert B Innis A1 Alison M Boyce YR 2020 UL http://jnm.snmjournals.org/content/early/2020/04/10/jnumed.120.241976.abstract AB McCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the GNAS gene, which encodes the 3′, 5′-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gsα. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the GNAS mutation during embryogenesis, the tissues involved, and the role of Gsα in the affected tissues. The Gsα mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP. Increased cAMP levels have been found in vitro in both animal models of fibrous dysplasia and in cultured cells from individuals with MAS, but not in humans with fibrous dysplasia. Positron emission tomography (PET) imaging of PDE4 with 11C-(R)-rolipram has been used successfully to study the in vivo activity of the cAMP cascade. To date, it remains unknown whether fibrous dysplasia and other symptoms of MAS, including neuropsychiatric impairments, are associated with increased PDE4 activity in humans. Methods: 11C-(R)-rolipram whole-body and brain PET scans were performed in six individuals with MAS (three for brain scans and six for whole-body scans) and nine healthy controls (seven for brain scans and six for whole-body scans). Results: 11C-(R)-rolipram binding correlated with known locations of fibrous dysplasia in the periphery of individuals with MAS; no uptake was observed in the bones of healthy controls. In peripheral organs and the brain, no difference in 11C-(R)-rolipram uptake was noted between participants with MAS and healthy controls. Conclusion: This study is the first to find evidence for increased cAMP activity in areas of fibrous dysplasia in vivo. No differences in brain uptake between MAS participants and controls were detected, which could be due to several reasons, including the limited anatomic resolution of PET. Nevertheless, the results confirm the usefulness of PET scans with 11C-(R)-rolipram to indirectly measure increased cAMP pathway activation in human disease.