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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F19%3A00510836" target="_blank" >RIV/86652036:_____/19:00510836 - isvavai.cz</a>

Result on the web

<a href="http://jnm.snmjournals.org/content/60/3/400" target="_blank" >http://jnm.snmjournals.org/content/60/3/400</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2967/jnumed.118.214403" target="_blank" >10.2967/jnumed.118.214403</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30224 - Radiology, nuclear medicine and medical imaging

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Nuclear Medicine

ISSN

0161-5505

e-ISSN

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Volume of the periodical

60

Issue of the periodical within the volume

3

Country of publishing house

US - UNITED STATES

Number of pages

7

Pages from-to

400-406

UT code for WoS article

000460125900017

EID of the result in the Scopus database

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