Pimonidazole is an anoxic marker used in studying intratumoral hypoxia and cell proliferation. Pimonidazole is a 2-nitroimidazole that is reductively activated specifically in hypoxic cells and forms stable adducts with thiol groups in proteins, peptides, and amino acids. The amount of Pimonidazole that is detected is directly proportional to the level of hypoxia within tumors [1-3].
Pimonidazole (80mg/kg; i.p) can be used to study hypoxia near necrosis of C6 rat brain glioma[4]. Pimonidazole can be used as an investigational hypoxia probe in clinical trials. Patients with primary cervical squamous cell carcinoma received a single infusion of Pimonidazole (0.5g/m²; i.v), followed by tumor biopsies 24 hours later. Immunohistochemical staining confirmed hypoxic cells, aiding tumor hypoxia assessment before radiation therapy[5]. 39 intermediate/high risk prostate cancer patients received a single oral dose of Pimonidazole (0.5g/m2) 24h prior to radical prostatectomy surgery. Pimonidazole-defined hypoxia intensity was positively correlated with advanced pathologic stage, tumor invasion, and cribriform and intraductal carcinoma morphology[6]. Pimonidazole can be used as an exogenous hypoxia marker for matrix-assisted laser desorption/ionization (MALDI) MSI. In hypoxic cells, Pimonidazole is reduced and forms reactive products that bind to thiol groups in proteins, peptides, and amino acids. A reductively activated Pimonidazole metabolite can be imaged by MALDI-MSI in a breast tumor xenograft model[7].
References:
[1]. Varia MA, Calkins-Adams DP, et,al. Pimonidazole: a novel hypoxia marker for complementary study of tumor hypoxia and cell proliferation in cervical carcinoma. Gynecol Oncol. 1998 Nov;71(2):270-7. doi: 10.1006/gyno.1998.5163. PMID: 9826471.
[2]. Inci ID, Tekin V, et,al. Radioiodination of Pimonidazole as a Novel Theranostic Hypoxia Probe. Curr Radiopharm. 2021;14(1):46-50. doi: 10.2174/1874471013666200331114908. PMID: 32228432.
[3]. Aguilera KY, Brekken RA. Hypoxia Studies with Pimonidazole in vivo. Bio Protoc. 2014 Oct 5;4(19):e1254. doi: 10.21769/bioprotoc.1254. PMID: 27453908; PMCID: PMC4956402.
[4]. Zoula S, Rijken PF, et,al. Pimonidazole binding in C6 rat brain glioma: relation with lipid droplet detection. Br J Cancer. 2003 May 6;88(9):1439-44. doi: 10.1038/sj.bjc.6600837. PMID: 12778075; PMCID: PMC2741029.
[5]. Kennedy AS, Raleigh JA, et,al. Proliferation and hypoxia in human squamous cell carcinoma of the cervix: first report of combined immunohistochemical assays. Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):897-905. doi: 10.1016/s0360-3016(96)00539-1. PMID: 9128967.
[6]. Ci X, Chen S, et,al. Oral pimonidazole unveils clinicopathologic and epigenetic features of hypoxic tumour aggressiveness in localized prostate cancer. BMC Cancer. 2024 Jun 18;24(1):744. doi: 10.1186/s12885-024-12505-1. PMID: 38890593; PMCID: PMC11186205.
[7]. Mascini NE, Cheng M, et,al. Mass Spectrometry Imaging of the Hypoxia Marker Pimonidazole in a Breast Tumor Model. Anal Chem. 2016 Mar 15;88(6):3107-14. doi: 10.1021/acs.analchem.5b04032. Epub 2016 Feb 29. PMID: 26891127.
Pimonidazole是一种缺氧标志物，用于肿瘤内缺氧和细胞增殖的研究。Pimonidazol是一种2-硝基咪唑，在缺氧细胞中被特异性还原激活，并与蛋白质、肽和氨基酸中的巯基形成稳定的加合物。Pimonidazole的检出量与肿瘤内缺氧程度成正比[1-3]。
Pimonidazole(80mg/kg; i.p)可用于研究C6大鼠脑胶质瘤坏死附近的缺氧情况[4]。Pimonidazole可用作临床试验中的研究性缺氧探针。患有原发性宫颈鳞状细胞癌的患者接受了单次pimonidazole (0.5g/m²; i.v)，24小时后进行肿瘤活检。免疫组化染色证实了缺氧细胞的存在，这有助于在放疗前评估肿瘤缺氧情况[5]。39名中高风险前列腺癌患者在接受根治性前列腺切除术前24小时单次口服Pimonidazole(0.5g/m2)。Pimonidazole定义的缺氧强度与晚期病理分期、肿瘤侵袭以及筛状和导管内癌形态呈正相关[6]。Pimonidazole可用作基质辅助激光解吸电离(MALDI)质谱成像(MSI)的外源性缺氧标志物。在缺氧细胞中，Pimonidazole被还原并形成可与蛋白质、肽和氨基酸中的巯基结合的反应性产物。还原激活的Pimonidazole代谢物可通过MALDI-MSI在乳腺肿瘤异种移植模型中成像[7]。