Journal
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
Volume 48, Issue 9, Pages 2846-2855Publisher
SPRINGER
DOI: 10.1007/s00259-021-05235-0
Keywords
C-11-MTP38; PDE7; Positron emission tomography; Quantification
Funding
- Japan Society for the Promotion of Science [19K17101]
- Grants-in-Aid for Scientific Research [19K17101] Funding Source: KAKEN
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The study successfully visualized PDE7 in human brains using PET imaging with C-11-MTP38, demonstrating the potential of this novel ligand for quantitative investigation of central PDE7. The results showed high retentions in specific brain regions and the reversibility of C-11-MTP38 binding, with excellent agreements between different quantification methods, suggesting the practicality of MRTMO and SUVR for clinical use of C-11-MTP38-PET.
Purpose Phosphodiesterase 7 (PDE7) is an enzyme that selectively hydrolyses cyclic adenosine monophosphate, and its dysfunction is implicated in neuropsychiatric diseases. However, in vivo visualization of PDE7 in human brains has hitherto not been possible. Using the novel PET ligand C-11-MTP38, which we recently developed, we aimed to image and quantify PDE7 in living human brains. Methods Seven healthy males underwent a 90-min PET scan after injection of C-11-MTP38. We performed arterial blood sampling and metabolite analysis of plasma in six subjects to obtain a metabolite-corrected input function. Regional total distribution volumes (V(T)s) were estimated using compartment models, and Logan plot and Ichise multilinear analysis (MA1). We further quantified the specific radioligand binding using the original multilinear reference tissue model (MRTMO) and standardized uptake value ratio (SUVR) method with the cerebellar cortex as reference. Results PET images with C-11-MTP38 showed relatively high retentions in several brain regions, including in the striatum, globus pallidus, and thalamus, as well as fast washout from the cerebellar cortex, in agreement with the known distribution of PDE7. V-T values were robustly estimated by two-tissue compartment model analysis (mean V-T = 4.2 for the pallidum), Logan plot, and MA1, all in excellent agreement with each other, suggesting the reversibility of C-11-MTP38 binding. Furthermore, there were good agreements between binding values estimated by indirect method and those estimated by both MRTMO and SUVR, indicating that these methods could be useful for reliable quantification of PDE7. Because MRTMO and SUVR do not require arterial blood sampling, they are the most practical for the clinical use of C-11-MTP38-PET. Conclusion We have provided the first demonstration of PET visualization of PDE7 in human brains. C-11-MTP38 is a promising novel PET ligand for the quantitative investigation of central PDE7.
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