Related Experiment Video
Updated: Jul 15, 2025
The Bioconjugation and Radiosynthesis of 89Zr-DFO-labeled Antibodies
Published on: February 12, 2015
Dosimetry of a Novel 111Indium-Labeled Anti-P-Cadherin Monoclonal Antibody (FF-21101) in Non-Human Primates
Gregory Ravizzini1, William Erwin2, Louis De Palatis3
1Department of Nuclear Medicine, University of Texas MD Anderson Cancer Center, 1400 Pressler St., Unit 1483, Houston, TX 77030, USA.
Abstract:
P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human-mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (111In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(111In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of 111In- and yttrium-90 (90Y)-FF-21101 for targeted radioimmunotherapy in humans. Whole-body planar and SPECT imaging were performed at 0, 2, 24, 48, 72, 96, and 120 h post-injection, using a dual-head gamma camera. Volumes of interest of identifiable source organs of radioactivity were defined on aligned reference CT and serial SPECT images. Organs with the highest estimated dose values (mSv/MBq) for FF-21101(111In) were the lungs (0.840), spleen (0.816), liver (0.751), kidneys (0.629), and heart wall (0.451); and for FF-21101(90Y) dose values were: lungs (10.49), spleen (8.21), kidneys (5.92), liver (5.46), and heart wall (2.61). FF-21101(111In) exhibits favorable biodistribution in cynomolgus macaques and estimated human dosimetric characteristics. Data obtained in this study were used to support the filing of an investigational new drug application with the FDA for a Phase I clinical trial.
Insights
This study evaluated FF-21101(111In) biodistribution in macaques, showing favorable characteristics for P-cadherin targeted radioimmunotherapy. The data supports its use in upcoming human clinical trials.
Area of Science:
- Oncology
- Nuclear Medicine
- Immunotherapy
Background:
- P-cadherin is a therapeutic target in various tumors.
- FF-21101 is a monoclonal antibody against P-cadherin, radioconjugated with 111In.
- Targeted radioimmunotherapy aims to deliver radiation directly to cancer cells.
Purpose of the Study:
- To investigate the biodistribution of FF-21101(111In) in cynomolgus macaques.
- To estimate internal radiation doses for 111In- and 90Y-FF-21101 in humans for radioimmunotherapy.
- To support an Investigational New Drug (IND) application for a Phase I clinical trial.
Main Methods:
- Whole-body planar and SPECT imaging of FF-21101(111In) in macaques.
- Analysis of radioactivity in organs using CT and SPECT imaging.
- Dosimetric calculations for 111In- and 90Y-FF-21101 based on biodistribution data.
Main Results:
- FF-21101(111In) demonstrated favorable biodistribution in macaques.
- Estimated highest radiation doses for 111In-FF-21101 were in lungs, spleen, liver, kidneys, and heart wall.
- Estimated highest radiation doses for 90Y-FF-21101 were also in lungs, spleen, kidneys, liver, and heart wall, with significantly higher values.
Conclusions:
- FF-21101(111In) exhibits promising biodistribution and dosimetric characteristics for targeted radioimmunotherapy.
- The study provides essential data for the clinical development of FF-21101.
- Results support the initiation of a Phase I clinical trial in humans.
