Mirzaei Mehdi, Mehravi Bita, Ardestani Mehdi Shafiee, Ziaee Seyed Amir Mohsen, Pourghasem Peyman
Labbafinejad Medical Center, Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, 9th Boustan, Pasdaran Ave, Tehran, Iran.
Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Mol Imaging Biol. 2015 Dec;17(6):770-6. doi: 10.1007/s11307-015-0841-9.
Early stage prostate cancer diagnosis is of high global interest. Magnetic resonance imaging (MRI) is a non-invasive modality for early cancer diagnosis, in particular for prostate cancer detection. The research aim is to synthesize a nanodendrimer and its conjugate with C595 monoclonal antibody (mAb C595), against prostate cancer, followed by its chelating with Gd(3+).
Anti-MUC-1 mAb C595 was conjugated to an anionic linear globular dendrimer (ALGDG2). The polyethylene glycol core and citric acid shell were synthesized followed by loading with Gd(3+) to make novel contrast agents for functional MRI. The in vitro behavior and MRI parameters of the nanoconjugate were investigated performing several studies such as cell toxicity and TNF-alpha evaluations. The investigation of magnetic resonance imaging parameters indicated how well nanoconjugate performs in (1)H-NMR and (17)O-NMR in vitro.
Results showed a potential specific MRI activity by improving the swelling responses cell binding. The MTT (2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide) assay demonstrated that this contrast agent had significant cytotoxicity on prostate cancer cells.
These results showed that Gd(3+)-ALGDG2-C595 is a potential prostate molecular imaging agent and could be considered as an ideal functional nanoprobe. Additionally, further investigations by clinical trials are in the pipeline.
早期前列腺癌诊断受到全球高度关注。磁共振成像(MRI)是一种用于早期癌症诊断的非侵入性方法,尤其适用于前列腺癌检测。研究目的是合成一种纳米树枝状大分子及其与抗前列腺癌的C595单克隆抗体(mAb C595)的缀合物,然后使其与Gd(3+)螯合。
抗MUC-1 mAb C595与阴离子线性球状树枝状大分子(ALGDG2)缀合。合成了聚乙二醇核心和柠檬酸外壳,随后负载Gd(3+)以制备用于功能MRI的新型造影剂。通过进行细胞毒性和TNF-α评估等多项研究,对纳米缀合物的体外行为和MRI参数进行了研究。磁共振成像参数的研究表明了纳米缀合物在体外(1)H-NMR和(17)O-NMR中的表现情况。
结果显示通过改善肿胀反应细胞结合具有潜在的特异性MRI活性。MTT(2-(4,5-二甲基-2-噻唑基)-3,5-二苯基-2H-四唑溴盐)试验表明这种造影剂对前列腺癌细胞具有显著的细胞毒性。
这些结果表明Gd(3+)-ALGDG2-C595是一种潜在的前列腺分子成像剂,可被视为一种理想的功能性纳米探针。此外,正在筹备进一步的临床试验研究。