Quantifying Gadolinium-Based, Theranostic Nanoparticle Uptake in MR Images of Pancreatic Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Nanomedicines are proving to be a viable option in improving radiotherapeutic benefits by amplifying the effects of radiotherapy. A recently developed, gadolinium (Gd) based theranostic agent has shown promise in the treatment of previously difficult to treat tumors. Here we examine, for the first time, uptake of this agent in patients with pancreatic cancer undergoing MR-guided adaptive radiotherapy. <h3>Materials/Methods</h3> Data have been acquired from four patients with pancreatic cancer enrolled in a stereotactic MR-guided adaptive radiotherapy clinical trial utilizing Gd-based nanoparticles (Nano-SMART). This trial has nanoparticles intravenously infused prior to MR simulation scanning (3T and 0.35T) and again prior to the first fraction (of five daily fractions). Physician-drawn contours were delineated on an MRI-guided real-time on-table adaptive radiotherapy 0.35T planning bSSFP scan. T1 maps of the abdomen were produced on a 3T scanner (a fully-body MRI scanner, from a technology company) before and after nanoparticle administration, using a prototype Look-Locker T1 mapping sequence with 28-30 slices (3 mm thickness, 1 mm spacing) and 244 × 244 pixels (1.56 × 1.56mm). Pre- and post- nanoparticle T1 maps were registered to the 0.35T planning images. Nanoparticle concentrations within contour defined volumes were calculated from T1 maps using the measured change in T1 values and a previously determined relaxivity constant (8.9 mM⁻¹s⁻¹). Average concentrations were compared across patients and anatomical structures. The use of an MR-Linac for adaptive radiotherapy enabled examination of nanoparticle uptake over time. MRI scans (bSSFP) were captured at each fraction, processed for bias field correction and normalized to spinal canal volumes; a region previously determined to not have significant uptake. Adapted contours defined fraction-specific volumes which were examined for patterns in signal intensity (SI) over time. <h3>Results</h3> Average T1 values for all targeted volumes (CTV, GTV) dropped after nanoparticle infusion. The amount of uptake varied significantly amongst patients but similarly amongst structures, with a notable initial concentration in the liver and kidneys. Fraction-specific MR scans indicated an approximate 20% drop in SI after the first fraction, followed by a more gradual loss of SI, suggesting a persistence of tumor uptake after initial administration. <h3>Conclusion</h3> We have demonstrated the ability to quantify nanoparticle uptake in patients with pancreatic cancer. Results indicate significant uptake of this new radiosensitizer agent in the pancreatic lesions as well as in the liver and kidneys. Follow-up scans and control subjects will inform tumor response due to nanoparticle-enhanced adaptive radiotherapy.