title: Development and evaluation of 99mTc-tricarbonyl-caspofungin as potential diagnostic agent of fungal infections.
abstract: Infections by Candida spp and Aspergillus spp are the most common causes of invasive fungal infections. The main diagnostic methods are blood culture, and antigen-based techniques, but they are still suboptimal, leading to delays in the initiation of therapies and resulting in high mortality rates despite the availability of several new antifungal agents. The aim of this work was the development, synthesis and evaluation of a potential radiopharmaceutical enable the rapid and accurate diagnosis by scintigraphic images of fungal infection using caspofungin, a lipopeptide, radiolabelled with (99m)Tc. Caspofungin was radiolabeled with (99m)Tc-tricarbonyl precursor. The complex was assessed for in vitro stability, lipophilicity, plasma protein binding and plasma stability. Biological evaluation was conducted in four groups of CD1 female mice. G1 healthy animals, G2 was induced sterile inflammation with turpentine oil. G3 and G4 were infected with Candida albicans and Aspergillus Niger. Scintigraphicimages were acquired before sacrifice. The Caspofungin - tricarbonyl complex was obtained with RCP higher than 95%, it was stable in labeling milieu for at least 20 hours, and in plasma for 4 hours. Challenge with competitive agents showed no ligand exchange during 200 min. The product was well tolerated by mice and showed mainly hepatobiliar excretion. Lesion uptake was markedly higher in infected tissues than in sterile inflammation. Scintigraphic images clearly distinguished inflammation from infection. The high RCP yields and in vitro stability, the targeted biodistribution profile and good T/NT ratios, outlines this complex as a potential agent for rapid and specific diagnosis of infections caused by pathogenic yeasts.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Reyes
authors.forename: Leticia
authors.initials: L
authors.lastname: Fernández
authors.forename: Ana
authors.initials: A
authors.lastname: Rey
authors.affiliation: Catedra de Radioquimica, Departamento Estrella Campos,Facultad de Quimica, Universidad de la Republica-Uruguay. MTERAN@FQ.EDU.UY.
authors.forename: Mariclla
authors.initials: M
authors.lastname: Terán
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000000981:diagnostic imaging*; D002177:Candidiasis / Q000000981:diagnostic imaging*; D000077336:Caspofungin; D002478:Cells, Cultured; D054714:Echinocandins; D005260:Female; D007553:Isotope Labeling; D055666:Lipopeptides; D051379:Mice; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013667:Technetium
chemical_list: D054714:Echinocandins; D055666:Lipopeptides; D019275:Radiopharmaceuticals; D013667:Technetium; D000077336:Caspofungin