Personalized Radionuclide Therapy via Avidin-Biotin Pretargeting: Biodistribution and Dosimetry of 177Lu-DOTA-biotin with AvidinOX™ in Solid Tumors.

PURPOSE: AvidinOX™ forms a long-lasting artificial receptor that supports effective in vivo binding of circulating biotinylated therapeutic 177Lu-DOTA-biotin. We investigated the biodistribution and radiation dosimetry of 177Lu-DOTA-biotin in patients with solid tumors following image-guided intratumoral AvidinOX administration.

METHODS

Three patients received intratumoral injections of AvidinOX and two cycles of intravenous administration of 177Lu-DOTA-biotin over a period of 2 weeks. Multi-time-point whole-body planar and SPECT/CT imaging was performed post infusion. Blood and urine samples were collected over 7 days, and organ radiation doses were estimated using the Medical Internal Radiation Dose methodology.

RESULTS

Sequential imaging demonstrated favorable tumor-to-background ratios and sustained uptake of 177Lu-DOTA-biotin within the pretargeted lesions, confirming effective localization and prolonged retention. Most of the administered activity was excreted via urine within 4 h post infusion. The absorbed tumor radiation dose ranged from 3.96 to 50.37 Gy, while bone marrow (0.15-0.22 Gy) and kidney (0.66-1.84 Gy) doses remained below established safety thresholds. There were no serious adverse events.

CONCLUSIONS

Intratumoral AvidinOX achieved effective and durable localization of 177Lu-DOTA-biotin without exceeding the maximum allowable radiation absorbed dose to critical organs. These first-in-human dosimetric data provide quantitative insight into tumor retention, off-target exposure, and therapeutic potential across solid tumors, supporting the rational design of future radionuclide therapy trials.