Diffusion-Weighted Imaging of a Prostate Cancer Xenograft Model Seen on a 7 Tesla Animal MR Scanner: Comparison of ADC Values and Pathologic Findings

Abstract

ObjectiveTo assess the relationship between apparent diffusion coefficient (ADC) values on diffusion-weighted magnetic resonance (MR) imaging and pathologic measures of a tumor using a prostate cancer xenograft model.Materials and MethodsEighteen athymic nude mice with 36 PC-3-induced tumors were sacrificed to obtain specimens immediately after MR imaging in order to compare the findings on MR images with those seen on pathological specimens. Using a high-field small-animal MR scanner, T1- and T2-weighted imaging and DW MR imaging was performed. Tumors were then processed for Hematoxylin and Eosin staining to evaluate tumor cellularity, intratumoral necrosis and immunostaining using antibodies directed against CD31 and vascular endothelial growth factor (VEGF) to determine the levels of microvessel density (MVD). Mean ADC values that were measured on the solid portion within each tumor were compared with tumor volume, cellularity, degree of necrosis, VEGF expression, and MVD in the corresponding section of the pathological specimen.ResultsMean ADC values of the solid portion within the PC-3-induced high-grade tumors were significantly correlated with the degree of intratumoral necrosis (r = 0.63, p < 0.0001) and MVD (r = -0.44, p = 0.008) on pathologic slides. The ADC values were not significantly correlated with tumor cellularity, VEGF expression, or tumor volume in high-grade prostate cancer tissues.ConclusionIn the xenografted prostate cancer model, the ADC values of the solid portion of the tumors are significantly correlated with tumor necrosis and MVD of the pathologic specimens. The ADC values may be utilized as surrogate markers for the noninvasive assessment of tumor necrosis and MVD in high-grade prostate cancer.

Enhanced binding of necrosis-targeting immunocytokine NHS-IL12 after local tumour irradiation in murine xenograft models

“…For PC3 tumours, TMR (d) and TKR (e) did not change after irradiation with 1 × 8.0 Gy and 5 × 2.0 Gy in comparison with unirradiated controls. Tumours are indicated with arrows, and statistical significance is indicated with * if p < 0.05 necrosis induction triggered by local irradiation in A204 xenografts, but in contrast to Jung et al [24], who described spontaneous necrosis without irradiation in PC3 tumours, we did not find necrosis in PC3 xenografts with our method of individually contoured tumour VOIs. For evaluation of the tumours, we defined the ADC90% value in analogy to Lu et al [26].…”

“…The coherence of high ADC values in MRI and histological findings of necrosis as well as an increase in ADC after irradiation of tumour xenografts has been shown previously for mean ADC of the whole tumour, mean ADC of a small VOI in the tumour and mean ADC of a central tumour slice [24,25]. In our study, MRI and histological findings show In A204 xenografts, an increased accumulation of radiolabelled NHS-IL12 was observed after irradiation with 1 × 8.0 Gy.…”

Evaluation of the efficacy of chemoradiotherapy in cervical cancer using diffusion-weighted imaging and apparent diffusion coefficient

“…The diffusion movement is restricted by the cell membrane and macromolecular substance and its restriction extent was determined by cell density, membrane integrity, viability, and structure and matrix composition 18. The possible mechanism is that as V pretreatment grows, cervical cancer cells show high growth and metabolism, intracellular protein increases, the nucleus grows, extracellular space decreases, and water molecule diffusion in the tumor tissues decreases, which thus leads to relatively low ADC pretreatment value 19. Relatively higher ADC pretreatment value indicates for the presence of necrotic tissues or damaged cell membrane tissues, which lead to poor blood flow perfusion.…”

Biexponential Apparent Diffusion Coefficients Values in the Prostate: Comparison among Normal Tissue, Prostate Cancer, Benign Prostatic Hyperplasia and Prostatitis

“…Several studies have shown that DWI has a high sensitivity and specificity for the detection and location of prostate cancer (8, 9), and a recent research also proved that the apparent diffusion coefficient (ADC) values of tumors were significantly correlated with that of tumor necrosis and microvessel density in high-grade prostate cancer, suggesting that DWI might be further used for the noninvasive evaluation of microscopic structures of the tumors (10). …”