A new ex vivo method to evaluate the performance of candidate MRI contrast agents: a proof-of-concept study.
BACKGROUND
Magnetic resonance imaging (MRI) plays an important role in tumor detection/diagnosis. The use of exogenous contrast agents (CAs) helps to improve the discrimination between lesion and neighbouring tissue, but most of the currently available CAs are non-specific. Assessing the performance of new, selective CAs requires exhaustive assays and large amounts of material. Accordingly, in a preliminary screening of new CAs, it is important to choose candidate compounds with good potential for in vivo efficiency. This screening method should reproduce as close as possible the in vivo environment. In this sense, a fast and reliable method to select the best candidate CAs for in vivo studies would minimize time and investment cost, and would benefit the development of better CAs.


RESULTS
The post-mortem ex vivo relative contrast enhancement (RCE) was evaluated as a method to screen different types of CAs, including paramagnetic and superparamagnetic agents. In detail, sugar/gadolinium-loaded gold nanoparticles (Gd-GNPs) and iron nanoparticles (SPIONs) were tested. Our results indicate that the post-mortem ex vivo RCE of evaluated CAs, did not correlate well with their respective in vitro relaxivities. The results obtained with different Gd-GNPs suggest that the linker length of the sugar conjugate could modulate the interactions with cellular receptors and therefore the relaxivity value. A paramagnetic CA (GNP (E_2)), which performed best among a series of Gd-GNPs, was evaluated both ex vivo and in vivo. The ex vivo RCE was slightly worst than gadoterate meglumine (201.9 ± 9.3% versus 237 ± 14%, respectively), while the in vivo RCE, measured at the time-to-maximum enhancement for both compounds, pointed to GNP E_2 being a better CA in vivo than gadoterate meglumine. This is suggested to be related to the nanoparticule characteristics of the evaluated GNP.


CONCLUSIONS
We have developed a simple, cost-effective relatively high-throughput method for selecting CAs for in vivo experiments. This method requires approximately 800 times less quantity of material than the amount used for in vivo administrations.
Ana Paula
AP
Candiota
Milena
M
Acosta
Rui Vasco
RV
Simões
Teresa
T
Delgado-Goñi
Silvia
S
Lope-Piedrafita
Ainhoa
A
Irure
Marco
M
Marradi
Oscar
O
Bomati-Miguel
Nuria
N
Miguel-Sancho
Ibane
I
Abasolo
Simó
S
Schwartz
Jesús
J
Santamaria
Soledad
S
Penadés
Centro de Investigación Biomédica en Red - Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain. carles.arus@uab.es.
Carles
C
Arús
D000818:Animals; D003287:Contrast Media / Q000737:chemistry; D005260:Female; D005682:Gadolinium / Q000737:chemistry; D005910:Glioma / Q000175:diagnosis; D006046:Gold / Q000737:chemistry; D006801:Humans; D007501:Iron / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry
D003287:Contrast Media; D006046:Gold; D005682:Gadolinium; D007501:Iron