P-2126. ‘SPECIFIC’ First-In-Human Clinical Trial of 68Ga-triacetylfusarinine (TAFC) Siderophore PET/CT for Detection of Invasive Aspergillosis

Abstract Background Invasive Aspergillus spp. infections (IAI) confer high morbidity and mortality in immunocompromised patients. Diagnosis often requires invasive and risky sampling. 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) is useful in diagnosis but is non-specific. Siderophores are pathogen-specific iron chelators which are a promising radiolabelling target for IAI diagnosis. Aspergillus fumigatus secretes 2 siderophores, fusarinine C and triacetylfusarinine (TAFC), which are upregulated during IAI. Gallium-68 (68Ga)-labelled TAFC is attractive due to its short half life, rapid renal clearance, and low radiation risk. Preclinical mouse studies demonstrate diagnostic potential of 68Ga-TAFC PET/CT with specific visualisation of A. fumigatus infection.Figure 1:68Ga-TAFC-PET/CT in a patient with leukemia and probable pulmonary A. fumigatus IAI. Specific infective uptake of known pulmonary lesions at around blood pool level intensity (SUVmax 3.5, SUVmean 2.3). There was minimal liver and marrow uptake, with progressive washout to 60 minutes. Methods We report the first result from a 10 patient pilot trial of 68Ga-TAFC PET/CT for IAI diagnosis (NCT06105411). Inclusion criteria are adults with pulmonary IAI within 2 weeks of diagnosis. Exclusion criteria are pregnant/lactating patients or those within a week of iron infusion. 68Ga-TAFC PET/CT was performed at 15, 62, and 209 minutes after IV 139 MBq 68Ga-TAFC administration. Findings pertinent to IAI and physiologic uptake were analysed. Results The patient had probable A. fumigatus IAI in the setting of leukemia. Galactomannan and Aspergillus fumigatus PCR were positive on bronchoalveolar lavage fluid. Empiric antifungal treatment was commenced with fever resolution at 72 hours. 68Ga-TAFC-PET/CT was performed 10 days after treatment start and 4 days after microbiological diagnosis. Blood pool activity (SUVmax at 15/60/209 mins: 4.1/2.7/1.9) was demonstrated with minimal liver, spleen and gastrointestinal tract uptake (SUVmax 2.7), early renal excretion, and no marrow or other organ uptake. There was focal uptake in multiple pulmonary lesions (SUVmax 3.5), similar to blood pool activity, with synchronous washout over time. No adverse effects occurred. Conclusion Very low background physiologic biodistribution was seen in the first participant in this study. Focal low grade pulmonary uptake was visualised, likely demonstrating specific activity for A.fumigatus. Trial recruitment continues. Disclosures Abby Douglas, MBBS, Gilead Sciences: Honoraria