Radiation absorbed dose estimation for 90Y-DOTA-biotin with pretargeted NR-LU-10/streptavidin

Area of Science:

• Nuclear medicine
• Oncology
• Radiotherapy

Background:

• Pretargeted radioimmunotherapy (PRIT) enables administration of significantly higher doses of Yttrium-90 (90Y) compared to conventional radioimmunotherapy.
• These escalated 90Y doses introduce novel dosimetry challenges not previously encountered.
• This study addresses these dosimetry issues and correlates them with clinical outcomes.

Purpose of the Study:

• To evaluate dosimetry methods for high-dose 90Y pretargeted radioimmunotherapy.
• To correlate dosimetry estimates with observed patient toxicity and tumor response.

Main Methods:

• Utilized a PRIT system with antibody NR-LU-10, streptavidin, and 90Y-DOTA-biotin, escalating 90Y doses up to 140 mCi/m2.
• Co-injected Indium-111 (111In) DOTA-biotin for gamma camera imaging and dosimetry.
• Developed methods to assess intestinal activity and calculate intestinal wall dose, identifying organs at risk.

Main Results:

• Bremsstrahlung radiation from 90Y constituted 12% of counts at a 90Y:111In ratio of 50:1.
• High-grade diarrhea (Grade IV) correlated with estimated large intestinal wall doses of 6850-14,000 cGy (r=0.64).
• Myelotoxicity correlated better with marrow dose (r=0.72) than whole-body dose (r=0.44); tumor response was observed with higher tumor doses (4,000-6,000 cGy).

Conclusions:

• Dosimetry is feasible with 111In as a tracer even with high 90Y activity.
• Estimated absorbed doses in the PRIT schema showed moderate correlation with observed clinical toxicity and treatment response.