RT Journal Article
SR Electronic
T1 [18F]Mefway is a promising candidate for human use to quantify serotonin 1A receptors
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1863
OP 1863
VO 57
IS supplement 2
A1 Choi, Jae Yong
A1 Lyoo, Chul Hyoung
A1 Kim, Kyeong Min
A1 Lee, Kyo Chul
A1 Ryu, Young Hoon
YR 2016
UL http://jnm.snmjournals.org/content/57/supplement_2/1863.abstract
AB 1863Objectives Alteration of the serotonin 1A receptor density is strongly implicated in the neuropsychiatric disorders such as depression, Schizophrenia and anxiety. Although many radiotracers have been developed to quantify the 5-HT1A receptors, there are few available PET radiotracers in human use. [18F]Mefway is an structural analogue of [18F]FCWAY to enhance metabolic stability. The purpose of the present study is to introduce [18F]Mefway as a promising candidate for clinical studies.Methods We tried to set up the optimized preparation method for [18F]Mefway. In this stage, we adapted the acid activation and the selective reduction system for the synthesis of the precursor. Then we developed a highly reliable radiofluorination method using automation module. After production method were established, the biological properties were examined. The specificity and selectivity of [18F]Mefway against the 5-HT1A receptors were validated in the rodents. The effect of the P-efflux transporters (i.e. P-gp and Bcrp) in the blood brain barrier were determined. Then it's the utility was evaluated in the animal disease models (i.e. Parkinson's model and depression model). Finally, we performed the comparison study between [18F]Mefway and [18F]FCWAY in human subject. In the PET experiments, dynamic PET scans were performed for 120 min. Non-displaceable binding potential (BPND) was used as an indication of receptor density and the cerebellum was used as the reference region.Results To be a successful PET radioligand, it must be satisfied the chemical reliability and efficacy in vivo. First of all, we have optimized preparation method for [18F]Mefway routine production. Then, we tested biological properties and the efficacy of [18F]Mefway. [18F]Mefway was underwent the in vivo defluorination in the rodents and this phenomena was inhibited by the pretreatment of fluconazole. In terms of the effect of efflux transporters in the blood brain barrer, [18F]Mefway was identified a substrate for P-glycoprotein in the rodent. In the animal disease models, BPND values in the Parkinson's disease and depression animal model were significantly reduced compared with those of the sham operated groups. In comparison study, although [18F]Mefway showed relatively lower brain uptake and binding values compared to [18F]FCWAY with disulfiram in human subjects, [18F]Mefway has reasonable binding value with little skull uptake.Conclusions [18F]Mefway may be a promising PET radiotracer for 5-HT1A receptor imaging in human