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

• Published in: International journal of molecular sciences Vol. 21; no. 7; p. 2304
• Main Authors: Sudo, Hitomi, Tsuji, Atsushi B, Sugyo, Aya, Kurosawa, Gene, Kurosawa, Yoshikazu, Alexander, David, Tsuda, Hiroyuki, Saga, Tsuneo, Higashi, Tatsuya
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.03.2020; MDPI
• Subjects: 5'-Nucleotidase - immunology; Adenosine; Affinity; Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Cancer therapies; cd73; CD73 antigen; Cell Line, Tumor; Computed tomography; Dosimetry; Ectonucleotidase; Evaluation; extracellular adenosine; Female; Flow cytometry; Humans; immune checkpoint; In vivo methods and tests; Indium Radioisotopes - chemistry; Medical imaging; Mice; Mice, Inbred BALB C; Mice, Nude; Monitoring; Monoclonal antibodies; Noninvasive evaluation; nuclear medicine imaging; Organs; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Sprague-Dawley; Single photon emission computed tomography; Single Photon Emission Computed Tomography Computed Tomography - methods; Spleen; stratification of patients; Tissue Distribution; tumor microenvironment; Tumors; CD73; Immune checkpoint; Tumor microenvironment; Nuclear Medicine imaging; Stratification of patients; Ectonucleotidase; Extracellular adenosine
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21072304

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 In-labeled antibody 067-213, which has high affinity for human CD73, to act as a noninvasive imaging probe. Cell binding and competitive inhibition assays for In-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. In-labeled 067-213 bound to MIAPaCa-2 and A431 cells in a CD73-dependent manner and the affinity loss after In-labeling was limited. Biodistribution and SPECT/CT studies with In-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. In-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.