UNLABELLED: The noninvasive imaging of σ-1 receptors (S1Rs) could provide insight into their role in different diseases and lead to novel diagnostic/treatment strategies. The main objective of this study was to assess the S1R radiotracer (18)F-FTC-146 in rats. Preliminary squirrel monkey imaging and human serum/liver microsome studies were performed to gain information about the potential of (18)F-FTC-146 for eventual clinical translation. METHODS: The distribution and stability of (18)F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid chromatography (HPLC). Preliminary PET/MRI of squirrel monkey brain was conducted along with HPLC assessment of (18)F-FTC-146 stability in monkey plasma and human serum. RESULTS: Biodistribution studies showed that (18)F-FTC-146 accumulated in S1R-rich rat organs, including the lungs, pancreas, spleen, and brain. Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P < 0.001), suggesting radiotracer specificity for S1Rs. Similarly, PET/CT and autoradiography results demonstrated accumulation of (18)F-FTC-146 in rat brain regions known to contain S1Rs and that this uptake could be blocked by BD1047 pretreatment. Ex vivo analysis of (18)F-FTC-146 in the brain showed that only intact radiotracer was present at 15, 30, and 60 min, whereas rapid metabolism of residual (18)F-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism, whereas (18)F-FTC-146 appeared to be stable in human serum. Finally, liver microsome studies revealed that (18)F-FTC-146 has a longer half-life in human microsomes, compared with rodents. CONCLUSION: Together, these results indicate that (18)F-FTC-146 is a promising tool for visualizing S1Rs in preclinical studies and that it has potential for mapping these sites in the human brain.
UNLABELLED: The noninvasive imaging of σ-1 receptors (S1Rs) could provide insight into their role in different diseases and lead to novel diagnostic/treatment strategies. The main objective of this study was to assess the S1R radiotracer (18)F-FTC-146 in rats. Preliminary squirrel monkey imaging and human serum/liver microsome studies were performed to gain information about the potential of (18)F-FTC-146 for eventual clinical translation. METHODS: The distribution and stability of (18)F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid chromatography (HPLC). Preliminary PET/MRI of squirrel monkey brain was conducted along with HPLC assessment of (18)F-FTC-146 stability in monkey plasma and human serum. RESULTS: Biodistribution studies showed that (18)F-FTC-146 accumulated in S1R-rich rat organs, including the lungs, pancreas, spleen, and brain. Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P < 0.001), suggesting radiotracer specificity for S1Rs. Similarly, PET/CT and autoradiography results demonstrated accumulation of (18)F-FTC-146 in rat brain regions known to contain S1Rs and that this uptake could be blocked by BD1047 pretreatment. Ex vivo analysis of (18)F-FTC-146 in the brain showed that only intact radiotracer was present at 15, 30, and 60 min, whereas rapid metabolism of residual (18)F-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism, whereas (18)F-FTC-146 appeared to be stable in human serum. Finally, liver microsome studies revealed that (18)F-FTC-146 has a longer half-life in human microsomes, compared with rodents. CONCLUSION: Together, these results indicate that (18)F-FTC-146 is a promising tool for visualizing S1Rs in preclinical studies and that it has potential for mapping these sites in the human brain.
Authors: K Ishiwata; H Tsukada; K Kawamura; Y Kimura; S Nishiyama; T Kobayashi; K Matsuno; M Senda Journal: Synapse Date: 2001-06-01 Impact factor: 2.562
Authors: Beatriz de la Puente; Xavier Nadal; Enrique Portillo-Salido; Ricard Sánchez-Arroyos; Sergio Ovalle; Gabriel Palacios; Asunción Muro; Luz Romero; José Manuel Entrena; José Manuel Baeyens; José Antonio López-García; Rafael Maldonado; Daniel Zamanillo; José Miguel Vela Journal: Pain Date: 2009-06-07 Impact factor: 6.961
Authors: Michelle L James; Bin Shen; Cristina L Zavaleta; Carsten H Nielsen; Christophe Mesangeau; Pradeep K Vuppala; Carmel Chan; Bonnie A Avery; James A Fishback; Rae R Matsumoto; Sanjiv S Gambhir; Christopher R McCurdy; Frederick T Chin Journal: J Med Chem Date: 2012-09-20 Impact factor: 7.446
Authors: Xuyi Yue; Hongjun Jin; Zonghua Luo; Hui Liu; Xiang Zhang; Ethan D McSpadden; Linlin Tian; Hubert P Flores; Joel S Perlmutter; Stanley M Parsons; Zhude Tu Journal: Bioorg Med Chem Date: 2017-01-16 Impact factor: 3.641
Authors: Trine Hjørnevik; Peter W Cipriano; Bin Shen; Jun Hyung Park; Praveen Gulaka; Dawn Holley; Harsh Gandhi; Daehyun Yoon; Erik S Mittra; Greg Zaharchuk; Sanjiv S Gambhir; Christopher R McCurdy; Frederick T Chin; Sandip Biswal Journal: J Nucl Med Date: 2017-06-01 Impact factor: 10.057
Authors: Talakad G Lohith; Rong Xu; Tetsuya Tsujikawa; Cheryl L Morse; Kacey B Anderson; Robert L Gladding; Sami S Zoghbi; Masahiro Fujita; Robert B Innis; Victor W Pike Journal: Synapse Date: 2014-08-11 Impact factor: 2.562
Authors: Bin Shen; Jun Hyung Park; Trine Hjørnevik; Peter W Cipriano; Daehyun Yoon; Praveen K Gulaka; Dawn Holly; Deepak Behera; Bonnie A Avery; Sanjiv S Gambhir; Christopher R McCurdy; Sandip Biswal; Frederick T Chin Journal: Mol Imaging Biol Date: 2017-10 Impact factor: 3.488
Authors: Bin Shen; Michelle L James; Lauren Andrews; Christopher Lau; Stephanie Chen; Mikael Palner; Zheng Miao; Natasha C Arksey; Adam J Shuhendler; Shawn Scatliffe; Kota Kaneshige; Stanley M Parsons; Christopher R McCurdy; Ahmad Salehi; Sanjiv S Gambhir; Frederick T Chin Journal: EJNMMI Res Date: 2015-09-17 Impact factor: 3.138
Authors: D L Bailey; B J Pichler; B Gückel; G Antoch; H Barthel; Z M Bhujwalla; S Biskup; S Biswal; M Bitzer; R Boellaard; R F Braren; C Brendle; K Brindle; A Chiti; C la Fougère; R Gillies; V Goh; M Goyen; M Hacker; L Heukamp; G M Knudsen; A M Krackhardt; I Law; J C Morris; K Nikolaou; J Nuyts; A A Ordonez; K Pantel; H H Quick; K Riklund; O Sabri; B Sattler; E G C Troost; M Zaiss; L Zender; Thomas Beyer Journal: Mol Imaging Biol Date: 2018-02 Impact factor: 3.488