²¹²Pb-conjugated anti-rat HER2/neu antibody against a neu-N derived murine mammary carcinoma cell line: cell kill and RBE in vitro

Abstract

Purpose

In the current work, the RBE of a ²¹²Pb-conjugated anti-HER2/neu antibody construct has been evaluated, in vitro, by colony formation assay. The RBE was estimated by comparing two absorbed dose-survival curves: the first obtained from the conjugated ²¹²Pb experiments (test radiation), the second obtained by parallel experiments of single bolus irradiation of external beam (reference radiation).

Materials and Methods

Mammary carcinoma NT2.5 cells were treated with (0–2.47) kBq/ml of radiolabeled antibody. Nonspecific binding was assessed with addition of excess amount of unlabeled antibody. The colony formation curves were converted from activity concentration to cell nucleus absorbed dose by simulating the decay and transport of all daughter and secondary particles of ²¹²Pb, using the Monte Carlo code GEANT 4.

Results

The radiolabeled antibody yielded an RBE of 11.5 at 37% survival and a survival independent RBE (i.e. RBE2) of 13.7. Unbound/untargeted ²¹²Pb-labeled antibody, as obtained in blocking experiments yielded minimal alpha-particle radiation to cells. Conclusions: These results further highlight the importance of specific targeting toward achieving tumor cell kill and low toxicity to normal tissue.

Keywords:

• Alpha particle
• LET radiation
• RBE
• radiosensitivity

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Correction

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/09553002.2023.2181604)

Disclosure statement

The authors have no conflicts or competing interests to disclose.

Additional information

Funding

This work was supported by National Institutes of Health (NIH) [grant: R01 CA116477].

Notes on contributors

Ioanna Liatsou

Dr. Ioanna Liatsou is a Research Associate at the Johns Hopkins University, School of Medicine, Department of Radiology and Radiological Science, and is a member of the Sgouros RTD Lab. Dr. Liatsou received her Bachelor of Science in Chemistry and her Master of Science and Ph.D. in Radioanalytical Chemistry with honors, from the University of Cyprus. She is a radiochemist with a wide range of expertise in radioanalytical chemistry and radiopharmaceutical therapy and her work is currently focused on targeted cancer therapy with the use of alpha particle emitter radiopharmaceuticals (αRPTs).

Jing Yu

Dr. Jing Yu was a postdoc research fellow at the Johns Hopkins School of Medicine, Department of Radiology and Radiological Science, and is now a Scientist at Johnson & Johnson. She received her bachelor degree in Chemical and Pharmaceutical Engineering at Southeast University, China. Dr. Yu earned her master degree in Pharmaceutical Science at Kanazawa University from Japan and Ph.D. degree in Chemistry from Kansas State University. Her research focused on cancer diagnosis and treatment with peptides and antibodies labeled with radio isotopes or fluorescence.

Remco Bastiaannet

Dr. Remco Bastiaannet is a Research Associate at the Radiological Physics Department in the Russell H. Morgan Department of Radiology and Radiological Science at Johns Hopkins Medicine. Dr. Bastiaannet received his Master of Science in Biomedical Engineering from the University of Twente and his PhD in the Medical Physics of Radiology and Nuclear Medicine from the University of Utrecht, The Netherlands. Dr. Bastiaannet’s research interests center on the quantification of radiation absorbed dose and dose-effect relationships in vivo, in vitro and in silico.

Zhi Li

Dr. Zhi Li is a senior research specialist at the Radiopharmaceutical Therapy and Dosimetry (RTD) Lab, Department of Radiology, Johns Hopkins University. Dr. Li received his PhD in Shanghai Brain Research Institute, Chinese Academy of Sciences in 2001. He joined the Department of Neuroscience at Hopkins as a postdoc in 2002 and was a research associate in the Department of Orthopedic Surgery before joining the RTD Lab.

Robert F. Hobbs

Dr. Robert Hobbs is an Associate Professor and has been a member of the Department of Radiology at Johns Hopkins since 2006. Dr. Hobbs’ primary appointment is in the department of Radiation Oncology, where he works in the clinic as an ABR certified Medical Physicist. Dr. Hobbs earned his undergraduate degrees (DEUG, License, Maîtrise) in Physics from the Université Louis Pasteur in Strasbourg, France, with a year spent at the Universität Wien (Vienna, Austria) as an ERASMUS exchange student. He earned his Ph.D. from the University of New Mexico in high energy Physics before joining the Sgouros lab as a post-doc in 2006. In 2011, he joined the department of Radiation Oncology as a Medical Physics resident. He received his ABR certification in 2014. Dr. Hobbs has been elected member of the MIRD (Medical Internal Radiation Dose) Committee and ais chair of the AAPM radiopharmaceutical therapy sub-committee (RPTSC).

Julien Torgue

Dr. Julien Torgue graduated from Florida Institute of Technology with a B.S. in Biochemistry, 2003, and a Ph.D. in molecular Biology, 2007. Dr. Torgue was elected member of the Macrocyclics board of directors in July 2015 and has been the Chief Scientific Officer at Orano Med, since 2010.

George Sgouros

Dr. George Sgouros is a Professor in the Johns Hopkins Medicine Department of Radiology and Radiological Science, Department of Radiation Oncology and Department of Oncology and a member of the Johns Hopkins Kimmel Cancer Center. His research focuses on modeling and dosimetry of internally administered radionuclides with a particular emphasis on patient-specific dosimetry, alpha-particle dosimetry, and mathematical modeling of radionuclide therapy. Dr. Sgouros is Director of the Radiological Physics Division of the Russell H. Morgan Department of Radiology and Radiological Science. Dr. Sgouros received his undergraduate degree in applied physics from Columbia University. He earned his Ph.D. from Cornell University and performed a fellowship in medical physics at Sloan Kettering Institute, Memorial Sloan-Kettering Cancer Center in New York. Dr. Sgouros joined the Johns Hopkins faculty in 2003.