Breast cancers: MR imaging of folate-receptor expression with the folate-specific nanoparticle P1133.
OBJECTIVE
To assess the capability of the folate receptor (FR)-targeted ultrasmall superparamagnetic iron oxide (USPIO) P1133 to provide FR-specific enhancement of breast cancers on magnetic resonance (MR) images.


METHODS
This study was approved by the institutional Animal Care and Use Committee. The FR-targeted contrast agent P1133 was incubated with various FR-positive human breast cancer cell lines, with and without free folic acid (FFA) as a competitor. Labeling efficiencies were evaluated with MR imaging and inductively coupled plasma mass spectrometry. Subsequently, six athymic rats with implanted FR-positive MDA-MB-231 breast cancers underwent MR imaging at 3 T before and up to 1 hour and 24 hours after injection of P1133. Six athymic rats with implanted FR-positive MDA-MB-231 cancers injected with the non-FR-targeted USPIO P904 and nine athymic rats with implanted FR-negative A549 lung cancers injected with P1133 (n = 6) or P904 (n = 3) served as controls. Data of the in vitro studies were compared for significant differences with the Wilcoxon test for two independent samples. Tumor signal-to-noise-ratios (SNRs) were compared between different experimental groups by using the Kruskal-Wallis test and were correlated with histopathologic findings. Differences with P < .05 were considered significant.


RESULTS
FR-positive breast cancer cells showed a significant P1133 uptake which was inhibited by FFA. MDA-MB-231 cells showed the highest level of P1133 uptake and the strongest T2 effect on MR images. In vivo, all tumors showed an initial perfusion effect. At 24 hours after injection, only MDA-MB-231 tumors injected with P1133 showed significantly decreased SNR data compared with baseline data (P < .05). MR findings were confirmed by using histopathologic findings.


CONCLUSIONS
The FR-targeted USPIO P1133 demonstrates a specific retention in FR-positive breast cancers. Because FR expression correlates with tumor aggressiveness and prognosis, persistent P1133 tumor enhancement may be used as a noninvasive indicator for tumors with poor outcome.
Meier
Reinhard
R
Department of Radiology, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143-0628, USA.
Henning
Tobias D
TD
Boddington
Sophie
S
Tavri
Sidhartha
S
Arora
Sandeep
S
Piontek
Guido
G
Rudelius
Martina
M
Corot
Claire
C
Daldrup-Link
Heike E
HE
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D053758:Nanoparticles; D051381:Rats; D011923:Rats, Nude; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D018709:Statistics, Nonparametric; D014183:Transplantation, Heterologous
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D011956:Receptors, Cell Surface; C097921:ferumoxtran-10; D005492:Folic Acid; C065507:ferumoxides; D052203:Ferrosoferric Oxide