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      Evaluation of 111In-DOTA-5D3, a Surrogate SPECT Imaging Agent for Radioimmunotherapy of Prostate-Specific Membrane Antigen

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          Abstract

          5D3 is a new high-affinity murine monoclonal antibody specific for prostate-specific membrane antigen (PSMA). PSMA is a target for the imaging and therapy of prostate cancer. 111In-labeled antibodies have been used as surrogates for 177Lu/ 90Y-labeled therapeutics. We characterized 111In-DOTA-5D3 by SPECT/CT imaging, tissue biodistribution studies, and dosimetry. Methods: Radiolabeling, stability, cell uptake, and internalization of 111In-DOTA-5D3 were performed by established techniques. Biodistribution and SPECT imaging were done on male nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice bearing human PSMA(+) PC3 PIP and PSMA(−) PC3 flu prostate cancer xenografts on the upper right and left flanks, respectively, at 2, 24, 48, 72, and 192 h after injection. Biodistribution was also evaluated in tumor-free, healthy male CD-1 mice. Blocking studies were performed by coinjection of a 10-fold and 50-fold excess of 5D3 followed by biodistribution at 24 h to determine PSMA binding specificity. The absorbed radiation doses were calculated on the basis of murine biodistribution data, which were translated to a human adult man using organ weights as implemented in OLINDA/EXM. Results: 111In-DOTA-5D3 was synthesized with specific activity of approximately 2.24 ± 0.74 MBq/μg (60.54 ± 20 μCi/μg). Distribution of 111In-DOTA-5D3 in PSMA(+) PC3 PIP tumor peaked at 24 h after injection and remained high until 72 h. Uptake in normal tissues, including the blood, spleen, liver, heart, and lungs, was highest at 2 h after injection. Coinjection of 111In-DOTA-5D3 with a 10- and 50-fold excess of nonradiolabeled antibody significantly reduced PSMA(+) PC3 PIP tumor and salivary gland uptake at 24 h but did not reduce uptake in kidneys and lacrimal glands. Significant clearance of 111In-DOTA-5D3 from all organs occurred at 192 h. The highest radiation dose was received by the liver (0.5 mGy/MBq), followed by the spleen and kidneys. Absorbed radiation doses to the salivary and lacrimal glands and bone marrow were low. Conclusion: 111In-DOTA-5D3 is a new radiolabeled antibody for imaging and a surrogate for therapy of malignant tissues expressing PSMA.

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          Author and article information

          Journal
          J Nucl Med
          J. Nucl. Med
          jnumed
          jnm
          Journal of Nuclear Medicine
          Society of Nuclear Medicine
          0161-5505
          1535-5667
          March 2019
          1 September 2019
          : 60
          : 3
          : 400-406
          Affiliations
          [1 ]Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland; and
          [2 ]Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Czech Republic
          Author notes
          For correspondence or reprints contact: Sangeeta Ray Banerjee, Johns Hopkins Medical Institutions, Cancer Research Building 2, 1550 Orleans St., Baltimore, MD 21287. E-mail: sray9@ 123456jhmi.edu

          Published online Sep. 20, 2018.

          Article
          PMC6424233 PMC6424233 6424233 214403
          10.2967/jnumed.118.214403
          6424233
          30237212
          1c769df9-9527-48ea-9794-8b25e425a8bd
          © 2019 by the Society of Nuclear Medicine and Molecular Imaging.
          History
          : 08 May 2018
          : 07 September 2018
          Page count
          Pages: 7
          Categories
          Theranostics
          Translational

          SPECT,monoclonal antibody,PSMA,SPECT/CT,immunoimaging,prostate cancer

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