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

0510836 - BTÚ 2020 RIV US eng J - Článek v odborném periodiku
Banerjee, S. R. - Kumar, V. - Lisok, A. - Plyku, D. - Nováková, Zora - Brummet, M. - Wharram, B. - Bařinka, Cyril - Hobbs, R. - Pomper, M.G.
Evaluation of In-111-DOTA-5D3, a Surrogate SPECT Imaging Agent for Radioimmunotherapy of Prostate-Specific Membrane Antigen.
Journal of Nuclear Medicine. Roč. 60, č. 3 (2019), s. 400-406. ISSN 0161-5505. E-ISSN 1535-5667
Institucionální podpora: RVO:86652036
Klíčová slova: SPECT/CT * immunoimaging * PSMA * monoclonal antibody
Obor OECD: Radiology, nuclear medicine and medical imaging
Impakt faktor: 7.887, rok: 2019
Způsob publikování: Open access
http://jnm.snmjournals.org/content/60/3/400

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. In-111-labeled antibodies have been used as surrogates for Lu-177/Y-90-labeled therapeutics. We characterized In-111-DOTA-5D3 by SPECT/CT imaging, tissue biodistribution studies, and dosimetry. Methods: Radiolabeling, stability, cell uptake, and internalization of In-111-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(1) 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: In-111-DOTA-5D3 was synthesized with specific activity of approximately 2.24 +/- 0.74 MBq/mu g (60.54 +/- 20 mu Ci/mu g). Distribution of In-111-DOTA-5D3 in PSMA(1) 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 In-111-DOTA-5D3 with a 10- and 50-fold excess of nonradiolabeled antibody significantly reduced PSMA(1) PC3 PIP tumor and salivary gland uptake at 24 h but did not reduce uptake in kidneys and lacrimal glands. Significant clearance of In-111-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: In-111-DOTA-5D3 is a new radiolabeled antibody for imaging and a surrogate for therapy of malignant tissues expressing PSMA.
Trvalý link: http://hdl.handle.net/11104/0301229