In Vitro Evaluation of Gd(3+)-Anionic Linear Globular Dendrimer-Monoclonal Antibody: Potential Magnetic Resonance Imaging Contrast Agents for Prostate Cancer Cell Imaging.
OBJECTIVE
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+).


METHODS
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
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.


CONCLUSIONS
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.
Labbafinejad Medical Center, Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, 9th Boustan, Pasdaran Ave, Tehran, Iran. dr_mehdimirzaei@yahoo.com.
Mehdi
M
Mirzaei
Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Bita
B
Mehravi
Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Mehdi Shafiee
MS
Ardestani
Labbafinejad Medical Center, Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, 9th Boustan, Pasdaran Ave, Tehran, Iran. samziaee@gmail.com.
Seyed Amir Mohsen
SA
Ziaee
Labbafinejad Medical Center, Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, 9th Boustan, Pasdaran Ave, Tehran, Iran.
Peyman
P
Pourghasem
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003287:Contrast Media; D005682:Gadolinium / Q000008:administration & dosage*; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018396:Mucin-1 / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D018796:Immunoconjugates; D018396:Mucin-1; D005682:Gadolinium
Anionic linear globular dendrimer; C595; MRI; MUC-1; Prostate cancer