DOI: 10.1177/10849785261458470 ISSN: 1084-9785

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

Xiaojuan Niu, Xiaoting Yang, Jianhua Jiao

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 177 Lu 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:

177 Lu-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.

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