Magnetic resonance imaging contrast enhancement in vitro and in vivo by octanuclear iron-oxo cluster-based agents.

A water-soluble octanuclear cluster, [Fe8], was studied with regard to its properties as a potential contrast enhancing agent in magnetic resonance imaging (MRI) in magnetic fields of 1.3, 7.2 and 11.9 T and was shown to have transverse relaxivities r2 = 4.01, 10.09 and 15.83 mM s-1, respectively. A related hydrophobic [Fe8] cluster conjugated with 5 kDa hyaluronic acid (HA) was characterized by 57Fe-Mössbauer and MALDI-TOF mass spectroscopy, and was evaluated in aqueous solutions in vitro with regard to its contrast enhancing properties [r2 = 3.65 mM s-1 (1.3 T), 26.20 mM s-1 (7.2 T) and 52.18 mM s-1 (11.9 T)], its in vitro cellular cytotoxicity towards A-549 cells and COS-7 cells and its in vivo enhancement of T2-weighted images (4.7 T) of a human breast cancer xenografted on a nude mouse. The physiologically compatible [Fe8]-HA conjugate was i.v. injected to the tumor-bearing mouse, resulting in observable, heterogeneous signal change within the tumor, evident 15 min after injection and persisting for approximately 30 min. Both molecular [Fe8] and its HA-conjugate show a strong magnetic field dependence on r2, rendering them promising platforms for the further development of T2 MRI contrast agents in high and ultrahigh magnetic fields.

Current and future applications of magnetic resonance imaging (MRI) to breast and ovarian cancer patient management.

Magnetic resonance imaging (MRI) is occupying an increasing niche in the clinical diagnostic workup of several cancers, including breast cancers. Despite the high level of implementation of mammography, it has become apparent that MRI can play at least a complementary role in the imaging and diagnosis of primary breast cancers, including ductal carcinoma in situ, the earliest stage of breast cancer that is associated with an increased risk of invasive breast cancer. This can also be said of inflammatory breast cancer, of low incidence but with high impact on overall breast cancer mortality rates, and for which mammography is not ideal due to the typically diffused nature of this disease. Much of the value of breast MRI is dependent on its high sensitivity, resulting from the use of contrast agent enhancement in the detection of breast cancer. Interest has also increased in the application of diffusion-weighted MRI for early assessment of treatment response in this disease. Regarding ovarian and other gynecological cancers, MRI has already demonstrated value in the evaluation of patients with ovarian masses, uterine leiomyoma, endometrioma, and cervical cancer. Features on MRI suggestive of malignant ovarian tumors are varied, and span irregular or solid components to a cystic mass, prominent septations, evidence of peritoneal, hematogenous, or lymphatic spread, or local invasion. The majority of ovarian malignancies are diagnosed in advanced, incurable stages, where exploratory laparotomy provides the opportunity for maximal debulking. Although a role for MRI has yet to be established in this initial setting or in staging, some studies have shown that high sensitivity may be achieved with contrast agent-enhanced MRI for detection of recurrent disease, including demonstration of macroscopic intraabdominal dissemination and the hallmark omental "cake". Efforts in recent years have been focused on design of MRI contrast agents (MRI-CAs), which either target biomarkers, or take advantage of the different physiology of cancerous cells. MRI-CAs based on gadolinium complexes, ferrumoxides, or other metallic nanoparticles have been investigated. This review will focus on the recent progress in the application of MRI to the imaging of breast and ovarian cancers, and present a possible role for molecularly-targeted contrast agents in enriching the context for MRI-based diagnosis.