Radiosynthesis of a carbon-11 labeled PDE5 inhibitor [11C]TPN171 as a new potential PET heart imaging agent

Challenges on Cyclic Nucleotide Phosphodiesterases Imaging with Positron Emission Tomography: Novel Radioligands and (Pre-)Clinical Insights since 2016

“…In 2017, Chekol et al [72] reported on two novel PDE5-specific radioligands, [ 11 C]15 and [ 18 F]16 (see Figure 4), for evaluation of the enzyme expression and occupancy in lung, heart and brain by PET. [76,77]as well as the PDE5 inhibitors tadalafil [78,79], vardenafil [78,80] and sildenafil [78][79][80].…”

“…Out of a series of pyridopyrazinone derivatives, compounds 15 and 16 showed highest inhibitory potency towards PDE5 (Figure 4) and were subsequently selected for radiolabeling. Starting from the corresponding desmethyl or tosylate precursors, [ 11 [76,77]as well as the PDE5 inhibitors tadalafil [78,79], vardenafil [78,80] and sildenafil [78][79][80].…”

“…Interestingly, highest radiochemical yields for automated radiosynthesis of [ 18 F]17 were achieved by using the nosylate precursor and [ 18 F]TBAF with the addition of small amounts of water to the reaction mixture [73]. 4) have been published by collaborating research groups from Hebei, China, and Indiana, USA [75,77]. Dong et al [75] focused on the PDE5 enzyme as a promising non-beta amyloid-related target for treatment and imaging of Alzheimer´s disease and thus, [ 11 C]19 and [ 11 C]20 were generated to investigate PDE5 in the brain by PET.…”

“…In 4) have been published by collaborating research groups from Hebei, China, and Indiana, USA [75,77]. Dong et al [75] focused on the PDE5 enzyme as a promising non-beta amyloid-related target for treatment and imaging of Alzheimer's disease and thus, [ 11 C]19 and [ 11 C]20 were generated to investigate PDE5 in the brain by PET.…”

“…Out of a series of novel naphthyridine and 1H-pyrroloquinolinone analogs [75,82], the most potent candidates 19 and 20 displayed picomolar inhibitory potency towards PDE5 and excellent selectivity over PDE6 (Figure 4), which shows high similarity in the catalytic site with PDE5 [82]. Besides, Xu et al [77] reported on the development of [ 11 C]21 for PET imaging of PDE5 in the heart. Briefly, the 4(3H)-pyrimidine lead compound 21 has previously been developed by Wang et al [76] as highly potent PDE5 inhibitor (Figure 4) for the treatment of pulmonary arterial hypertension and is currently being investigated in a phase II clinical trial.…”