Preclinical Evaluation of a Novel High-Affinity Radioligand [ 99mTc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA)

Bibliografiska uppgifter
Parent link:International Journal of Molecular Sciences.— .— Basel: MDPI AG
Vol. 24 - iss.24.— 2023.— Article number 17391, 24p.
Övriga upphovsmän: Bezverkhniaia E. A. Ekaterina Aleksandrovna, Kanellopoulos P. Panagiotis, Abouzayed A. Ayman, Larkina M. S. Mariya Sergeevna, Oroujeni M. Maryam, Vorobjeva (Vorobyeva) A. G. Anzhelika Grigorjevna, Rosenstrom U. Ulrika, Tolmachev V. M. Vladimir Maksimilianovich, Orlova A. M. Anna Markovna
Sammanfattning:Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl–triglutamate chelator for labeling with Tc99m (designated as BQ0413). The purpose of this study was to evaluate the imaging properties of [99mTc]Tc-BQ0413. PSMA-transfected PC3-pip cells were used to evaluate the specificity and affinity of [99mTc]Tc-BQ0413 binding in vitro. PC3-pip tumor-bearing BALB/C nu/nu mice were used as an in vivo model. [99mTc]Tc-BQ0413 bound specifically to PC3-pip cells with an affinity of 33 ± 15 pM. In tumor-bearing mice, the tumor uptake of [99mTc]Tc-BQ0413 (38 ± 6 %IA/g in PC3-pip 3 h after the injection of 40 pmol) was dependent on PSMA expression (3 ± 2 %IA/g and 0.9 ± 0.3 %IA/g in PSMA-negative PC-3 and SKOV-3 tumors, respectively). We show that both unlabeled BQ0413 and the commonly used binder PSMA-11 enable the blocking of [99mTc]Tc-BQ0413 uptake in normal PSMA-expressing tissues without blocking the uptake in tumors. This resulted in an appreciable increase in tumor-to-organ ratios. At the same injected mass (5 nmol), the use of BQ0413 was more efficient in suppressing renal uptake than the use of PSMA-11. In conclusion, [99mTc]Tc-BQ0413 is a promising probe for the visualization of PSMA-positive lesions using single-photon emission computed tomography (SPECT).
Текстовый файл
Språk:engelska
Publicerad: 2023
Ämnen:
Länkar:https://doi.org/10.3390/ijms242417391
http://apex.tpu.ru/ap/PUBLIKACIYA.ORIGINAL_PUBL1?p_image_id=113631&p_session_id=109393972742875
Materialtyp: Elektronisk Bokavsnitt
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=672736

MARC

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200 1 |a Preclinical Evaluation of a Novel High-Affinity Radioligand [ 99mTc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA)  |f E. Bezverkhniaia, P. Kanellopoulos, A. Abouzayed [et al.]  |d Доклиническая оценка нового высокоаффинного радиолиганда [99mTc] Tc-BQ0413, нацеленного на простатспецифический мембранный антиген (PSMA)  |z rus 
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330 |a Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl–triglutamate chelator for labeling with Tc99m (designated as BQ0413). The purpose of this study was to evaluate the imaging properties of [99mTc]Tc-BQ0413. PSMA-transfected PC3-pip cells were used to evaluate the specificity and affinity of [99mTc]Tc-BQ0413 binding in vitro. PC3-pip tumor-bearing BALB/C nu/nu mice were used as an in vivo model. [99mTc]Tc-BQ0413 bound specifically to PC3-pip cells with an affinity of 33 ± 15 pM. In tumor-bearing mice, the tumor uptake of [99mTc]Tc-BQ0413 (38 ± 6 %IA/g in PC3-pip 3 h after the injection of 40 pmol) was dependent on PSMA expression (3 ± 2 %IA/g and 0.9 ± 0.3 %IA/g in PSMA-negative PC-3 and SKOV-3 tumors, respectively). We show that both unlabeled BQ0413 and the commonly used binder PSMA-11 enable the blocking of [99mTc]Tc-BQ0413 uptake in normal PSMA-expressing tissues without blocking the uptake in tumors. This resulted in an appreciable increase in tumor-to-organ ratios. At the same injected mass (5 nmol), the use of BQ0413 was more efficient in suppressing renal uptake than the use of PSMA-11. In conclusion, [99mTc]Tc-BQ0413 is a promising probe for the visualization of PSMA-positive lesions using single-photon emission computed tomography (SPECT). 
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461 1 |c Basel  |n MDPI AG  |t International Journal of Molecular Sciences 
463 1 |d 2023  |t Vol. 24 - iss.24  |v Article number 17391, 24p. 
610 1 |a prostate cancer 
610 1 |a prostate-specific membrane antigen 
610 1 |a PSMA 
610 1 |a technetium-99m 
610 1 |a BQ0413 
610 1 |a single-photon emission computed tomography 
610 1 |a труды учёных ТПУ 
610 1 |a электронный ресурс 
701 1 |a Bezverkhniaia  |b E. A.  |c pharmacist  |c Research Engineer Tomsk Polytechnic University  |f 1994-  |g Ekaterina Aleksandrovna  |9 22467 
701 1 |a Kanellopoulos  |b P.  |g Panagiotis 
701 1 |a Abouzayed  |b A.  |g Ayman 
701 1 |a Larkina  |b M. S.  |g Mariya Sergeevna  |f 1984-  |c pharmacist  |c Professor; Senior Researcher of the Tomsk Polytechnic University, Doctor of Pharmaceutical Sciences  |9 22417 
701 1 |a Oroujeni  |b M.  |g Maryam 
701 1 |a Vorobjeva (Vorobyeva)  |b A. G.  |c specialist in the field of medical technology  |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D  |f 1990-  |g Anzhelika Grigorjevna  |9 22214 
701 1 |a Rosenstrom  |b U.  |g Ulrika 
701 1 |a Tolmachev  |b V. M.  |c specialist in the field of medical technology  |c Director of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D  |f 1961-  |g Vladimir Maksimilianovich  |9 22210 
701 1 |a Orlova  |b A. M.  |c specialist in the field of medical technology  |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D  |f 1960-  |g Anna Markovna  |9 22212 
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