Evaluation of genotoxic potential of peptides used in nuclear medicine (PSMA -617 and -11, and ubiquicidine 29-41) using a flow-cytometric, semi-automated analysis of micronuclei frequency in cell cultures

被引:2
作者
de Carvalho, L. R. [1 ]
Vieira, D. P. [1 ]
机构
[1] Inst Pesquisas Energet & Nucl, Ctr Biotecnol, Lab Radiobiol, Av Lineu Prestes 2242, Sao Paulo, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Radiopharmaceuticals; Genotoxicity; Micronucleus; Flow-cytometry; PSMA; UBI; MEMBRANE ANTIGEN-EXPRESSION; PERIPHERAL-BLOOD; ASSAY; INFECTION; INHIBITORS; LIGANDS;
D O I
10.1016/j.toxrep.2020.02.003
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Assays that rely on the assessment of frequency of micronuclei are important standard techniques currently used to quantify potential genotoxic damage after exposure to chemical or physical agents, such as ionizing radiation, or in pre-clinical studies, to assessment of the genotoxic potential of drugs or its components. The experiments are usually performed using conventional microscopy, but currently the protocols are being upgraded to automated approaches based on flow cytometry protocols based on the elimination of the plasma membrane by chemical agents, allowing quantification by flow cytometry. In this work, the genotoxic potential of peptides used as components of radiopharmaceuticals (PSMA-617 and 11 and Ubiquicidine) was evaluated exposing CHO-KI cells to a wide range of concentration (0.1X and 100X the maximum allowed concentration to human adults). Incubation with PSMA-11 or UBI29-41 did not induce genotoxicity. After 24 h of incubation, PSMA-617 induced genotoxicity only in non-practical concentration (100-fold). Results corroborate the safety of the pre-drugs and the wide detection range of technique.
引用
收藏
页码:304 / 316
页数:13
相关论文
共 39 条
[31]  
OECD, 2014, 487 OECD TG, P1, DOI [10.1017/CBO9781107415324.004., DOI 10.1017/CBO9781107415324.004]
[32]   A Pooled Analysis of Diagnostic Value of 99mTc-Ubiquicidin (UBI) Scintigraphy in Detection of an Infectious Process [J].
Ostovar, Afshin ;
Assadi, Mahsan ;
Vahdat, Katayoun ;
Nabipour, Iraj ;
Javadi, Hamid ;
Eftekhari, Mohammad ;
Assadi, Majid .
CLINICAL NUCLEAR MEDICINE, 2013, 38 (06) :413-416
[33]   Multiagent imaging of inflammation and infection with radionuclides [J].
Palestro C.J. ;
Glaudemans A.W.J.M. ;
Dierckx R.A.J.O. .
Clinical and Translational Imaging, 2013, 1 (6) :385-396
[34]   Repairing DNA-methylation damage [J].
Sedgwick, B .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (02) :148-157
[35]   Further evaluation of a flow cytometric in vitro micronucleus assay in CHO-K1 cells: a reliable platform that detects micronuclei and discriminates apoptotic bodies [J].
Shi, Jing ;
Bezabhie, Rahel ;
Szkudlinska, Anna .
MUTAGENESIS, 2010, 25 (01) :33-40
[36]  
Shields AF, 2003, J NUCL MED, V44, P1432
[37]  
Silver DA, 1997, CLIN CANCER RES, V3, P81
[38]   44Sc-PSMA-617 for radiotheragnostics in tandem with 177Lu-PSMA-617-preclinical investigations in comparison with 68Ga-PSMA-11 and 68Ga-PSMA-617 [J].
Umbricht, Christoph A. ;
Benesova, Martina ;
Schmid, Raffaella M. ;
Turler, Andreas ;
Schibli, Roger ;
van der Meulen, Nicholas P. ;
Mueller, Cristina .
EJNMMI RESEARCH, 2017, 7
[39]   NAAG peptidase inhibitors and their potential for diagnosis and therapy [J].
Zhou, J ;
Neale, JH ;
Pomper, MG ;
Kozikowski, AP .
NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (12) :1015-1026