Early detection of radiation therapy response in non‐Hodgkin's lymphoma xenografts byin vivo¹H magnetic resonance spectroscopy and imaging

Abstract

The purpose of the study was to investigate the capability of (1)H MRS and MRI methods for detecting early response to radiation therapy in non-Hodgkin's lymphoma (NHL). Studies were performed on the WSU-DLCL2 xenograft model in nude mice of human diffuse large B-cell lymphoma, the most common form of NHL. Radiation treatment was applied as a single 15 Gy dose to the tumor. Tumor lactate, lipids, total choline, T(2) and apparent diffusion coefficients (ADC) were measured before treatment and at 24 h and 72 h after radiation. A Hadamard-encoded slice-selective multiple quantum coherence spectroscopy sequence was used for detecting lactate (Lac) while a stimulated echo acquisition mode sequence was used for detection of total choline (tCho) and lipids. T(2)- and diffusion-weighted imaging sequences were used for measuring T(2) and ADC. Within 24 h after radiation, significant changes were observed in the normalized integrated resonance intensities of Lac and the methylenes of lipids. Lac/H(2)O decreased by 38 +/- 15% (p = 0.03), and lipid (1.3 ppm, CH(2))/H(2)O increased by 57 +/- 14% (p = 0.01). At 72 h after radiation, tCho/H(2)O decreased by 45 +/- 14% (p = 0.01), and lipid (2.8 ppm, polyunsaturated fatty acid)/H(2)O increased by 970 +/- 36% (p = 0.001). ADC increased by 14 +/- 2% (p = 0.003), and T(2) did not change significantly. Tumor growth delay and regression were observed thereafter. This study enabled comparison of the relative sensitivities of various (1)H MRS and MRI indices to radiation and suggests that (1)H MRS/MRI measurements detect early responses to radiation that precede tumor volume changes.

Whole-Body Diffusion-weighted MR Imaging in Cancer: Current Status and Research Directions

“…Preclinical studies show that ADC increases occur rapidly in tumors that are radiation sensitive ( 125 ), with changes visible as early as 24-72 hours after a single large radiation fraction ( 126 ). This fi nding occurred in the absence of a change in tumor size and coincided with metabolic disruption shown with proton MR spectroscopy ( 126 ).…”

Repeatability of edited lactate and other metabolites in astrocytoma at 3T

“…For example, tumors can contain large amounts of lactate, and an early drop in the lactate signal may be a sensitive measure of response to therapy (2)(3)(4). Conversely, increases in lactate in normalappearing peritumoral regions may predict progression (5).…”

Exploiting tumor metabolism for non-invasive imaging of the therapeutic activity of molecularly targeted anticancer agents

“…18,42 Although FDG-PET has been the main metabolic imaging modality for studying tumor glycolytic activity in patients, both 1 H and 13 C MRS have been useful for monitoring glucose uptake and lactate production in pre-clinical cancer models at baseline and following radiation or cytotoxic drug treatment. 44,45 The alterations in tumor metabolism detectable by imaging methods such as MRS and PET are being investigated as noninvasive diagnostic as well as treatment response biomarkers. 14,46 In the context of targeted therapeutics, the knowledge that oncogene activation impacts on several metabolic processes creates exciting new opportunities for using metabolism as a tool for discovering PD biomarkers for oncogenic signaling inhibitors as well as agents acting on metabolic pathways.…”