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The invasion status of tumour-draining lymph nodes (LNs) is a critical indicator of cancer stage and is important for treatment planning. Clinicians currently use planar scintigraphy and single-photon emission computed tomography (SPECT) with 99mTc-radiocolloid to guide biopsy and resection of LNs. However, emerging multimodality approaches such as positron emission tomography combined with magnetic resonance imaging (PET/MRI) detect sites of disease with higher sensitivity and accuracy. Here we present a multimodal nanoparticle, 89Zr-ferumoxytol, for the enhanced detection of LNs with PET/MRI. For genuine translational potential, we leverage a clinical iron oxide formulation, altered with minimal modification for radiolabelling. Axillary drainage in naive mice and from healthy and tumour-bearing prostates was investigated. We demonstrate that 89Zr-ferumoxytol can be used for high-resolution tomographic studies of lymphatic drainage in preclinical disease models. This nanoparticle platform has significant translational potential to improve preoperative planning for nodal resection and tumour staging.

In vivo knowledge of the spatial distribution of viable, necrotic, and hypoxic areas can provide prognostic information about the risk of developing metastases and regional radiation sensitivity and may be used potentially for localized dose escalation in radiation treatment. In this study, multimodality in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging using stereotactic fiduciary markers in the Dunning R3327-AT prostate tumor were performed, focusing on the relationship between dynamic contrast-enhanced (DCE) MRI using Magnevist (Gd-DTPA) and dynamic (18)F-fluoromisonidazole ((18)F-Fmiso) PET. The noninvasive measurements were verified using tumor tissue sections stained for hematoxylin/eosin and pimonidazole. To further validate the relationship between (18)F-Fmiso and pimonidazole uptake, (18)F digital autoradiography was performed on a selected tumor and compared with the corresponding pimonidazole-stained slices. The comparison of Akep values (kep = rate constant of movement of Gd-DTPA between the interstitial space and plasma and A = amplitude in the two-compartment model (Hoffmann U, Brix G, Knopp MV, Hess T and Lorenz WJ (1995). Magn Reson Med 33, 506-514) derived from DCE-MRI studies and from early (18)F-Fmiso uptake PET studies showed that tumor vasculature is a major determinant of early (18)F-Fmiso uptake. A negative correlation between the spatial map of Akep and the slope map of late (last 1 hour of the dynamic PET scan) (18)F-Fmiso uptake was observed. The relationships between DCE-MRI and hematoxylin/eosin slices and between (18)F-Fmiso PET and pimonidazole slices confirm the validity of MRI/PET measurements to image the tumor microenvironment and to identify regions of tumor necrosis, hypoxia, and well-perfused tissue.

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A double-delay SR-MGE-SNAP sequence allowing simultaneous T1 and T2* measurement was developed for integrating arterial input function (AIF) measurement into DCE MRI. Implemented on a 4.7-T animal MR system, this technique was applied to mice with colorectal tumor xenografts. AIF, measured in the mouse heart, was modeled by a bi-exponential function, whereas tumor K(trans) and v(e) parameter maps were obtained from analysis with a two- compartment model using an individually measured AIF. AIF analysis of T2*-corrected data yielded A1 = 9.2 +/- 4.3 kg/l, A(2) = 4.2 +/- 0.8 kg/l, m1 = 2.3 +/- 1.1 min(-1), and m2 = 0.05 +/- 0.02 min(-1). The mean initial plasma concentration C ( p )(t = 0) = 8.0 +/- 2.7 mM was compatible with estimated 8.6 mM. Without T2*-correction distribution phase parameters A1, m1, and C(p)(t = 0) were underestimated. In tumors, neglect of T2* effects yielded mean K(trans) values which were reduced by 14% (P < 0.05), whereas v(e) showed only a slight non-significant reduction. Simultaneous measurement of DeltaR1 and DeltaR2* studied in highly and poorly vascularized and (pre-)necrotic tumor regions revealed complementary behavior of both parameters with respect to vascular properties. In conclusion, the presented measurement technique is a promising tool for dynamic MRI applications studied in animal models at high field strengths and/or with CA of high relaxivities, as it combines classical DCE MRI integrating AIF assessment with dynamic T2* measurement.