Bone Marrow Relative Biological Effectiveness for a 212Pb-labeled Anti-HER2/neu Antibody

Ioanna Liatsou, Anders Josefsson, Jing Yu, Angel Cortez, Remco Bastiaannet, Esteban Velarde, Kaori Davis, Cory Brayton, Hao Wang, Julien Torgue, Robert F. Hobbs, George Sgouros

Research output: Contribution to journalArticlepeer-review


Purpose: We have determined the in vivo relative biological effectiveness (RBE) of an alpha-particle–emitting radiopharmaceutical therapeutic agent (212Pb-labeled anti-HER2/neu antibody) for the bone marrow, a potentially dose-limiting normal tissue. Methods and Materials: The RBE was measured in mice using femur marrow cellularity as the biological endpoint. External beam radiation therapy (EBRT), delivered by a small-animal radiation research platform was used as the reference radiation. Alpha-particle emissions were delivered by 212Bi after the decay of its parent nuclide 212Pb, which was conjugated onto an anti-HER2/neu antibody. The alpha-particle absorbed dose to the marrow after an intravenous administration (tail vein) of 122.1 to 921.3 kBq 212Pb-TCMC-7.16.4 was calculated. The mice were sacrificed at 0 to 7 days after treatment and the radioactivity from the femur bone marrow was measured. Changes in marrow cellularity were assessed by histopathology. Results: The dose response for EBRT and 212Pb-anti-HER2/neu antibody were linear-quadratic and linear, respectively. On transforming the EBRT dose-response relationship into a linear relationship using the equivalent dose in 2-Gy fractions of external beam radiation formalism, we obtained an RBE (denoted RBE2) of 6.4, which is independent of cellularity and absorbed dose. Conclusions: Because hematologic toxicity is dose limiting in almost all antibody-based RPT, in vivo measurements of RBE are important in helping identify an initial administered activity in phase 1 escalation trials. Applying the RBE2 and assuming typical antibody clearance kinetics (biological half-life of 48 hours), using a modified blood-based dosimetry method, an average administered activity of approximately 185.5 MBq (5.0 mCi) per patient could be administered before hematologic toxicity is anticipated.

Original languageEnglish (US)
Pages (from-to)518-528
Number of pages11
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number2
StatePublished - Feb 1 2023

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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