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Dosimetry of a Novel (111)Indium-Labeled Anti-P-Cadherin Monoclonal Antibody (FF-21101) in Non-Human Primates
SIMPLE SUMMARY: This research study focuses on the P-cadherin protein, which is found in many types of tumors, and could be a potential target for therapy. FF-21101, a human–mouse chimeric monoclonal antibody that targets P-cadherin, was labeled with indium-111((111)In) and investigated for biodistr...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526467/ https://www.ncbi.nlm.nih.gov/pubmed/37760501 http://dx.doi.org/10.3390/cancers15184532 |
Sumario: | SIMPLE SUMMARY: This research study focuses on the P-cadherin protein, which is found in many types of tumors, and could be a potential target for therapy. FF-21101, a human–mouse chimeric monoclonal antibody that targets P-cadherin, was labeled with indium-111((111)In) and investigated for biodistribution and radiation doses in six cynomolgus macaques. To assess the radiation profile distribution and clearance of FF-21101((111)In), we performed whole-body imaging and generated time–activity curves. The lungs, spleen, liver, kidneys, and heart wall received the highest radiation dose estimates for FF-21101((111)In). These findings led us to estimate the radiation doses that would be delivered to different organs if this antibody was labeled with yttrium-90 ((90)Y) and used in targeted radioimmunotherapy in patients. FF-21101 shows potential for clinical application in humans, according to biodistribution data obtained from macaques. Based on these results, an investigational new drug application was filed with the FDA for a Phase I clinical trial. 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 ((111)In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101((111)In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of (111)In- and yttrium-90 ((90)Y)-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((111)In) were the lungs (0.840), spleen (0.816), liver (0.751), kidneys (0.629), and heart wall (0.451); and for FF-21101((90)Y) dose values were: lungs (10.49), spleen (8.21), kidneys (5.92), liver (5.46), and heart wall (2.61). FF-21101((111)In) 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. |
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