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

Abstract

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.