| Full text | |
| Author(s): Show less - |
Ortega Pijeira, Martha Sahyli
[1]
;
Goncalves Nunes, Paulo Sergio
[2]
;
dos Santos, Sofia Nascimento
[1]
;
Zhang, Zhengxing
[3]
;
Nario, Arian Perez
[1]
;
Perini, Efrain Araujo
[1]
;
Turato, Walter Miguel
[4]
;
Riera, Zalua Rodriguez
[5]
;
Chammas, Roger
[6]
;
Elsinga, Philip H.
[7]
;
Lin, Kuo-Shyan
[3]
;
Carvalho, Ivone
[2]
;
Bernardes, Emerson Soares
[1]
Total Authors: 13
|
| Affiliation: | [1] Nucl & Energy Res Inst IPEN CNEN SP, Radiopharm Ctr, BR-05508000 Sao Paulo - Brazil
[2] Univ Sao Paulo FCFRP USP, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto - Brazil
[3] BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3 - Canada
[4] Univ Sao Paulo, Sch Pharmaceut Sci, BR-05508000 Sao Paulo - Brazil
[5] Univ La Habana, Dept Radioquim, Inst Super Tecnol & Ciencias Aplicadas InSTEC, Havana 10400 - Cuba
[6] Univ Sao Paulo, Fac Med, Dept Radiol & Oncol, BR-01246903 Sao Paulo - Brazil
[7] Univ Groningen, Univ Med Ctr Groningen, Dept Nucl Med & Mol Imaging, EB79, POB 30-001, NL-9700 RB Groningen - Netherlands
Total Affiliations: 7
|
| Document type: | Journal article |
| Source: | Molecules; v. 25, n. 8 APR 2 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
Losartan is widely used in clinics to treat cardiovascular related diseases by selectively blocking the angiotensin II type 1 receptors (AT(1)Rs), which regulate the renin-angiotensin system (RAS). Therefore, monitoring the physiological and pathological biodistribution of AT(1)R using positron emission tomography (PET) might be a valuable tool to assess the functionality of RAS. Herein, we describe the synthesis and characterization of two novel losartan derivatives PET tracers, {[}F-18]fluoroethyl-losartan ({[}F-18]FEtLos) and {[}F-18]ammoniomethyltrifluoroborate-losartan ({[}F-18]AMBF(3)Los). {[}F-18]FEtLos was radiolabeled by F-18-fluoroalkylation of losartan potassium using the prosthetic group 2-{[}F-18]fluoroethyl tosylate; whereas {[}F-18]AMBF(3)Los was prepared following an one-step F-18-F-19 isotopic exchange reaction, in an overall yield of 2.7 +/- 0.9% and 11 +/- 4%, respectively, with high radiochemical purity (>95%). Binding competition assays in AT(1)R-expressing membranes showed that AMBF(3)Los presented an almost equivalent binding affinity (K-i 7.9 nM) as the cold reference Losartan (K-i 1.5 nM), unlike FEtLos (K-i 2000 nM). In vitro and in vivo assays showed that {[}F-18]AMBF(3)Los displayed a good binding affinity for AT(1)R-overexpressing CHO cells and was able to specifically bind to renal AT(1)R. Hence, our data demonstrate {[}F-18]AMBF(3)Los as a new tool for PET imaging of AT(1)R with possible applications for the diagnosis of cardiovascular, inflammatory and cancer diseases. (AU) | |
| FAPESP's process: | 12/06875-6 - Development and production of positron emission tomography radiopharmaceuticals for diagnostic purposes in oncology |
| Grantee: | Emerson Soares Bernardes |
| Support Opportunities: | Research Grants - Young Investigators Grants |