Synthesis and Evaluation of [F-18]FEtLos and [F-18]AMBF(3)Los as Novel F-18-Labelled Losartan Derivatives for Molecular Imaging of Angiotensin II Type 1 Receptors

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

Radiolabeled nanomaterials for biomedical applications: radiopharmacy in the era of nanotechnology

Background: Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. Nanomedicine, a term for the application of nanotechnology in medical and health fields, uses nanoparticles for several applications such as imaging, diagnostic, targeted cancer therapy, drug and gene delivery, tissue engineering, and theranostics. Results: Here, we overview the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and radionuclide therapy. Nanostructured radiopharmaceuticals of technetium-99m, copper-64, lutetium-177, and radium-223 are discussed within the scope of this review article. Conclusion: Nanoradiopharmaceuticals may lead to better development of theranostics inspired by ingenious delivery and imaging systems. Cancer nano-theranostics have the potential to lead the way to more specific and individualized cancer treatment.Technology Agency of the Czech Republic [TO01000074, TJ04000129]; Ministry of Education, Youth and Sports [8J20PL016]; FAPERJ: Cientista do Nosso Estado [E-26/200.815/2021]; CNPq: Bolsa de Produtividade [301069/2018-2]; FAPERJ: Rede NanoSaude [E-26/010.000981/2019]Technology Agency of the Czech Republic Grant Nos.: TO01000074, TJ04000129, Ministry of Education, Youth and Sports under Grant No.: 8J20PL016. FAPERJ: Cientista do Nosso Estado (E-26/200.815/2021), Rede NanoSaude (E-26/010.000981/2019) and CNPq: Bolsa de Produtividade (301069/2018-2)

Folic acid-functionalized graphene quantum dots: Synthesis, characterization, radiolabeling with radium-223 and antiviral effect against Zika virus infection

The use of graphene quantum dots as biomedical devices and drug delivery systems has been increasing. The nano-platform of pure carbon has shown unique properties and is approved to be safe for human use. In this study, we successfully produced and characterized folic acid-functionalized graphene quantum dots (GQD-FA) to evaluate their antiviral activity against Zika virus (ZIKV) infection in vitro, and for radiolabeling with the alpha -pArticle emitting radionuclide radium-223. The in vitro results exhibited the low cytotoxicity of the nanoprobe GQD-FA in Vero E6 cells and the antiviral effect against replication of the ZIKV infection. In addition, our findings demonstrated that functionalization with folic acid doesn't improve the antiviral effect of graphene quantum dots against ZIVK replication in vitro. On the other hand, the radiolabeled nanoprobe 223Ra@GQD-FA was also produced as confirmed by the Energy Dispersive X-Ray Spectroscopy analysis. 223Ra@GQD-FA might expand the application of alpha targeted therapy using radium-223 in folate receptor-overexpressing tumors.This study was funded by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ) (Cientista do Nosso Estado: E-26/200.815/2021; Rede NanoSaude: E-26/010.000981/2019, Pesquisa na UEZO: E-26/010.002362/2019; Tematicos: E-26/211.269/2021, Infraestrutura e Pesquisa na UEZO e UERJ: E-26//211.207/2021, Bolsa de Pos Doutorado Senior (PDS): E-26/202.320/2021) CNPq (Bolsa de Produtividade 1B: 301069/2018-2) to Ralph Santos-Oliveira. National Nuclear Energy Commission (Bolsa de Posdoutorado CNEN: 01341.011064/2021-71) to Martha Sahyli Ortega Pijeira.Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ) [E-26/200.815/2021, E-26/010.000981/2019, E-26/010.002362/2019, E-26/211.269/2021, E-26//211.207/2021, E-26/202.320/2021]; CNPq [301069/2018-2]; National Nuclear Energy Commission [01341.011064/2021-71