TY - JOUR
T1 - Dosimetry of a Novel 111Indium-Labeled Anti-P-Cadherin Monoclonal Antibody (FF-21101) in Non-Human Primates
AU - Ravizzini, Gregory
AU - Erwin, William
AU - De Palatis, Louis
AU - Martiniova, Lucia
AU - Subbiah, Vivek
AU - Paolillo, Vincenzo
AU - Mitchell, Jennifer
AU - McCoy, Asa P.
AU - Gonzalez, Jose
AU - Mawlawi, Osama
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
KW - CDH3
KW - internal radiation dosimetry
KW - non-human primates
KW - radioimmunotherapy
KW - SPECT
KW - theranostics
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U2 - 10.3390/cancers15184532
DO - 10.3390/cancers15184532
M3 - Article
C2 - 37760501
AN - SCOPUS:85172768838
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 18
M1 - 4532
ER -