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Open AccessArticle

Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression

1
Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Inage, Chiba 263-8555, Japan
2
International Center for Cell and Gene Therapy, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
3
Department of Innovation Center for Advanced Medicine, Research Promotion Support Center, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
4
Nanotoxicology Project, Nagoya City University, 3-1 Tanabe-dohri, Mizuho-ku, Nagoya 466-8603, Japan
5
Department of Advanced Medical Imaging Research, Graduate School of Medicine, Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2304; https://doi.org/10.3390/ijms21072304
Received: 21 February 2020 / Revised: 19 March 2020 / Accepted: 19 March 2020 / Published: 26 March 2020
(This article belongs to the Special Issue Cancer Molecular Imaging)
Background: CD73 is an ectonucleotidase regulating extracellular adenosine concentration and plays an important role in adenosine-mediated immunosuppressive pathways. The efficacy of CD73-targeted therapy depends on the expression levels of CD73; therefore, monitoring CD73 status in cancer patients would provide helpful information for selection of patients who would benefit from CD73-targeted therapy. Here, we evaluated the ability of 111In-labeled antibody 067-213, which has high affinity for human CD73, to act as a noninvasive imaging probe. Methods: Cell binding and competitive inhibition assays for 111In-labeled 067-213 were conducted using MIAPaCa-2 (high CD73 expression) and A431 (low CD73 expression) cells. For in vivo assessments, biodistribution and SPECT/CT studies were conducted in MIAPaCa-2 and A431 tumor-bearing mice. To estimate the absorbed dose in humans, biodistribution and SPECT/CT studies were conducted in healthy rats. Results: 111In-labeled 067-213 bound to MIAPaCa-2 and A431 cells in a CD73-dependent manner and the affinity loss after 111In-labeling was limited. Biodistribution and SPECT/CT studies with 111In-labeled 067-213 in mice showed high uptake in MIAPaCa-2 tumors and lower uptake in A431 tumors. In rats, the probe did not show high uptake in normal organs, including endogenously CD73-expressing organs. The estimated absorbed doses in humans were reasonably low. Conclusions: 111In-labeled 067-213 showed CD73-expression-dependent tumor uptake and low uptake in normal organs and tissues. Radiolabeled 067-213 holds promise as an imaging probe for noninvasive evaluation of CD73 expression levels in patients. Our data encourage further clinical studies to clarify a role for CD73 monitoring in patients receiving CD73-targeted immune therapy. View Full-Text
Keywords: CD73; immune checkpoint; ectonucleotidase; extracellular adenosine; tumor microenvironment; nuclear medicine imaging; stratification of patients CD73; immune checkpoint; ectonucleotidase; extracellular adenosine; tumor microenvironment; nuclear medicine imaging; stratification of patients
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Sudo, H.; Tsuji, A.B.; Sugyo, A.; Kurosawa, G.; Kurosawa, Y.; Alexander, D.; Tsuda, H.; Saga, T.; Higashi, T. Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression. Int. J. Mol. Sci. 2020, 21, 2304.

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