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Clin Nucl Med ; 47(12): 1026-1029, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2078007


PATIENTS AND METHODS: Six post COVID-19 patients suspected for pulmonary fibrosis were scheduled for dual-tracer PET/CT with 18 F-FDG and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46. The uptake of 68 Ga-FAPI-46 in the involved lung was compared with a control group of 9 non-COVID-19 patients. Clinical data and PET/CT imaging were collected and analyzed. RESULTS: PET/CT revealed in all 6 pulmonary impaired patients the reduced glucose avidity on 18 F-FDG and clear positivity on 68 Ga-FAPI-46 PET/CT in comparison to the control group. CONCLUSIONS: Enhancing fibrotic repair mechanisms, 68 Ga-FAPI PET/CT may improve noninvasive clinical diagnostic performance in patients with long-term CT abnormalities after severe COVID-19. Although this study shows promising results, additional studies in larger populations are required to establish a general diagnostic guideline.

COVID-19 , Positron Emission Tomography Computed Tomography , Humans , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18 , Membrane Proteins/metabolism , COVID-19/complications , COVID-19/diagnostic imaging , Gallium Radioisotopes
Anal Biochem ; 632: 114384, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1415148


Invasive pulmonary aspergillosis (IPA) is a severe life-threatening condition. Diagnosis of fungal disease in general, and especially that caused by Aspergillus fumigatus is problematic. A. fumigatus secretes siderophores to acquire iron during infection, which are also essential for virulence. We describe the chemoacetylation of ferrated fusarinine C to diacetylated fusarinine C (DAFC), followed by protein conjugation, which facilitated triacetylfusarinine C (TAFC)-specific monoclonal antibody production with specific recognition of the ferrated form of TAFC. A single monoclonal antibody sequence was ultimately elucidated by a combinatorial strategy involving protein LC-MS/MS, cDNA sequencing and RNAseq. The resultant murine IgG2a monoclonal antibody was secreted in, and purified from, mammalian cell culture (5 mg) and demonstrated to be highly specific for TAFC detection by competitive ELISA (detection limit: 15 nM) and in a lateral flow test system (detection limit: 3 ng), using gold nanoparticle conjugated- DAFC-bovine serum albumin for competition. Overall, this work reveals for the first time a recombinant TAFC-specific monoclonal antibody with diagnostic potential for IPA diagnosis in traditional and emerging patient groups (e.g., COVID-19) and presents a useful strategy for murine Ig sequence determination, and expression in HEK293 cells, to overcome unexpected limitations associated with aberrant or deficient murine monoclonal antibody production.

Antibodies, Monoclonal/immunology , Aspergillosis/diagnosis , Ferric Compounds/immunology , Hydroxamic Acids/immunology , Immunoconjugates/chemistry , Siderophores/chemistry , Animals , Aspergillosis/microbiology , Aspergillus fumigatus/chemistry , Aspergillus fumigatus/pathogenicity , Enzyme-Linked Immunosorbent Assay , Ferric Compounds/analysis , HEK293 Cells , Humans , Hydroxamic Acids/analysis , Mice , Recombinant Proteins/immunology