Clinical Laboratory Evaluation of the Biodistribution of a Radiolabeled Antimicrobial Peptide for Precision Radiopharmaceutical-Guided Radionuclide Therapy in Severe Pneumonia Among Immunocompromised Patients with Cancer.

Abstract

Background: Pneumonia in immunocompromised patients with cancer is associated with high morbidity, diagnostic uncertainty, and poor short-term outcomes. Precision radiopharmaceutical approaches may improve lesion localization, biodistribution assessment, and patient-specific treatment planning in this vulnerable population group.

Methods: The authors conducted a prospective single-arm study of a DOTA-functionalized antimicrobial peptide radiolabeled with ¹⁷⁷Lu in immunocompromised patients with cancer with severe pneumonia. The study evaluated the radiochemical performance, in vitro stability, clinical biodistribution, pulmonary lesion localization, quantitative uptake kinetics, lesion dosimetry, short-term clinical response, and safety. The full cohort included 50 patients, with imaging- and dosimetry-evaluable subgroups of 5 and 15 patients, respectively.

Results: The radiopharmaceutical demonstrated high radiochemical purity (98.5%) and favorable labeling efficiency, with optimal radiolabeling achieved at 60°C. Whole-body planar imaging and thoracic SPECT/CT revealed persistent pulmonary lesion uptake with improved delayed lesion conspicuity. In the imaging subgroup, the lesion-to-blood pool and lesion-to-normal lung ratios increased over time, indicating progressive lesion contrast. Dosimetric analysis showed the highest absorbed dose in pulmonary lesions (∼4.5 Gy/GBq), exceeding the doses to the kidneys, liver, normal lung, and blood. Eleven of the 15 dosimetry-evaluable patients exceeded the predefined lesion-to-kidney dose ratio threshold of >2.0. Clinically, 35 of the 50 patients (70%) improved, 10 (20%) remained stable, and 5 (10%) worsened. No grade 4 adverse events were observed, and treatment-related toxicities were predominantly grades 1-2.

Conclusions: ¹⁷⁷Lu-labeled antimicrobial peptide imaging demonstrated favorable radiochemical characteristics, persistent pulmonary lesion targeting, clinically relevant dosimetric selectivity, and an acceptable short-term safety profile in immunocompromised patients with cancer with severe pneumonia. These findings support the translational potential of this peptide-based radiopharmaceutical as a theranostic platform for imaging-guided dosimetry-informed precision management.