INTRODUCTION: Invasive pulmonary aspergillosis (IPA) is a leading cause of infection-associated death in immunosuppressed patients. Early detection and early administration of antifungal therapy are critical factors in improving outcome for patients with IPA. Here, we evaluated the imaging properties of a (111)In-labeled cyclic peptide targeted to Aspergillus fumigatus in an immunosuppressed murine model of IPA. METHODS: A cyclic peptide c(CGGRLGPFC)-NH(2) was labeled with (111)In by means of diethylenetriaminepentaacetic acid (DTPA). Two days after intranasal inoculation of 17.5x10(6) conidia of A. fumigatus, mice were injected (111)In-DTPA-c(CGGRLGPFC)-NH(2) intravenously. Biodistribution data were obtained at 2 h, and gamma-images were acquired at 10 min and 2 h after radiotracer injection. Healthy mice were used as controls. In addition, a group of infected mice were co-injected with the radiotracer and unlabeled c(CGGRLGPFC)-NH(2) to evaluate the inhibition of radiotracer's binding to infected lungs. Autoradiographs of lungs from infected and healthy mice were compared with corresponding photographs of transaxial sections of the lung tissues stained for A. fumigatus hyphae. RESULTS: The labeling efficiency was >98%, with specific radioactivity of up to 74 MBq/nmol peptide. Significantly higher uptake of (111)In-DTPA-c(CGGRLGPFC)-NH(2) was observed in the lungs of mice infected with A. fumigatus than in those of healthy mice (0.37+/-0.06 %ID/g vs. 0.14+/-0.02 %ID/g, P=.00044). Simultaneous injection with unlabeled peptide reduced radioactivity in the infected lungs by 41% (P=.0037). Increased radioactivity in the lungs of infected mice was visible in gamma images at both 10 min and 2 h after radiotracer injection. Moreover, autoradiography confirmed radiotracer uptake in infected lungs, but not in the lungs of healthy mice or infected mice co-injected with unlabeled peptide. CONCLUSIONS: Gamma-imaging with (111)In-DTPA-c(CGGRLGPFC)-NH(2) clearly delineated experimental IPA in mice. Peptides directly targeting fungi therefore may be valuable agents for noninvasive detection of opportunistic mycoses.
INTRODUCTION:Invasive pulmonary aspergillosis (IPA) is a leading cause of infection-associated death in immunosuppressed patients. Early detection and early administration of antifungal therapy are critical factors in improving outcome for patients with IPA. Here, we evaluated the imaging properties of a (111)In-labeled cyclic peptide targeted to Aspergillus fumigatus in an immunosuppressed murine model of IPA. METHODS: A cyclic peptide c(CGGRLGPFC)-NH(2) was labeled with (111)In by means of diethylenetriaminepentaacetic acid (DTPA). Two days after intranasal inoculation of 17.5x10(6) conidia of A. fumigatus, mice were injected (111)In-DTPA-c(CGGRLGPFC)-NH(2) intravenously. Biodistribution data were obtained at 2 h, and gamma-images were acquired at 10 min and 2 h after radiotracer injection. Healthy mice were used as controls. In addition, a group of infected mice were co-injected with the radiotracer and unlabeled c(CGGRLGPFC)-NH(2) to evaluate the inhibition of radiotracer's binding to infected lungs. Autoradiographs of lungs from infected and healthy mice were compared with corresponding photographs of transaxial sections of the lung tissues stained for A. fumigatus hyphae. RESULTS: The labeling efficiency was >98%, with specific radioactivity of up to 74 MBq/nmol peptide. Significantly higher uptake of (111)In-DTPA-c(CGGRLGPFC)-NH(2) was observed in the lungs of mice infected with A. fumigatus than in those of healthy mice (0.37+/-0.06 %ID/g vs. 0.14+/-0.02 %ID/g, P=.00044). Simultaneous injection with unlabeled peptide reduced radioactivity in the infected lungs by 41% (P=.0037). Increased radioactivity in the lungs of infected mice was visible in gamma images at both 10 min and 2 h after radiotracer injection. Moreover, autoradiography confirmed radiotracer uptake in infected lungs, but not in the lungs of healthy mice or infected mice co-injected with unlabeled peptide. CONCLUSIONS: Gamma-imaging with (111)In-DTPA-c(CGGRLGPFC)-NH(2) clearly delineated experimental IPA in mice. Peptides directly targeting fungi therefore may be valuable agents for noninvasive detection of opportunistic mycoses.
Authors: Milos Petrik; Hubertus Haas; Georg Dobrozemsky; Cornelia Lass-Flörl; Anna Helbok; Michael Blatzer; Hermann Dietrich; Clemens Decristoforo Journal: J Nucl Med Date: 2010-04 Impact factor: 10.057