MR/NIRF Dual-Mode Imaging of αvß3 Integrin-Overexpressing Tumors Using a Lipopeptide-Based Contrast Agent.

Early diagnosis and noninvasive detection of hepatocellular carcinoma have profound clinical implications for treatment quality and improved prognosis. To obtain high-resolution macroscopic anatomical information and high-sensitivity microscopic optical signals to detect tumors, it is highly desirable to develop dual-mode magnetic resonance imaging (MRI) and near-infrared fluorescent (NIRF) probes. An MR/NIRF dual-mode targeted contrast agent was created by encapsulating cyclic arginine-glycine-aspartate (cRGD) and Cy5.5 in liposomes and characterized by the particle size distribution, cytotoxicity, targeting, and MRI relaxivity. The MR T2 intensity and fluorescence intensity were evaluated in the tumors, livers, and muscles after the injection of cRGD-Liposome-Cy5.5 and Liposome-Cy5.5 at different time points. The average size of cRGD-Liposome-Cy5.5 was 62.33 ± 4.648 nm. The transverse relaxivity (R2) values had a negative correlation with the concentration of molecular probes. The MR signal intensity was enhanced in tumors after the cRGD-Liposome-Cy5.5 injection and not enhanced in liver parenchyma and muscles at the same time. The fluorescence intensity was enhanced in tumors after cRGD-Liposome-Cy5.5 injection in the targeted group. cRGD -Liposome-Cy5.5 as an entirely organic T2-positive dual-mode MR/NIRF targeted contrast agent is therefore able to detect early-stage hepatocellular carcinoma by targeting integrin αvß3, providing advantages for potential clinical utility and ease of clinical transformation.

Changes in Apparent Diffusion Coefficient as Surrogate Marker for Changes in Ki-67 Index Due to Neoadjuvant Chemotherapy in Patients with Invasive Breast Cancer.

RATIONALE AND OBJECTIVES: To evaluate possible correlation between changes in apparent diffusion coefficient (ADC) and Ki-67 index as a result of neoadjuvant chemotherapy (NAC) in patients with invasive breast cancer. METHODS AND MATERIALS: Between February 2016 and October 2017, 87 patients with breast cancer underwent diffusion-weighted magnetic resonance imaging (b = 0 and 800 sec/mm2) before and after NAC. ADC and tumor diameter before and after NAC were compared to the Ki-67 index determined from biopsy or surgical specimens. RESULTS: Ki-67 index did not correlate significantly with ADC before NAC (p = 0.862) or afterwards (p = 0.292), nor did it correlate with tumor diameter before (p = 0.545) or afterwards (p = 0.478). However, change in ADC as a result of NAC correlated inversely with change in Ki-67 index (r = -0.326, p = 0.002). The percentage change in Ki-67 index did not correlate with the percentage change in ADC (p = 0.404). Similarly, the change in Ki-67 index or percentage change in that index did not correlate with the change in tumor diameter (p = 0.075) or percentage change in tumor diameter (p = 0.233). CONCLUSION: Comparison of pre- and post-NAC ADC can be used to estimate the change in Ki-67 index in patients with invasive breast cancer.

Synthesis and In Vitro Study of a Dual-Mode Probe Targeting Integrin αvß3.

Malignant tumors constitute a serious disease that threaten human life, and early diagnosis and metastasis prediction are critical to the choice of treatment plan and the timing of treatment. Integrin αvß3, which has received broad attention as a molecular marker of the tumor neovasculature, is an important target for monitoring tumorigenesis and progression in molecular imaging research. This study reports a magnetic resonance (MR)/fluorescence dual-mode molecular probe, cRGD-Gd-Cy5.5, which targets the integrin αvß3 receptor and uses liposomes as carrier. The obtained nanoprobe had a size of 60.08 ± 0.45 nm, with good dispersion in water, a uniform distribution of sizes, desirable stability, and high relaxivity. Its r1 relaxation rate was 10.515 mM-1 s-1, much higher than that of other Gd chelates in clinical use. The probe showed no cytotoxicity at the tested concentrations in vitro, and its ability to target A549 cells and SUNE-1-5-8F cells was preliminarily evaluated through in vitro fluorescence imaging and MR imaging. The results demonstrated that the cRGD-Gd-Cy5.5 nanoprobe had good characteristics, showing desirable stability and biosafety, a high T1 relaxation rate, and strong targeting and binding to tumors with high expression of integrin αvß3. Therefore, cRGD-Gd-Cy5.5 is a promising agent for the visual monitoring of tumor metastasis.

Diagnostic value of diffusion-weighted magnetic resonance imaging for local and skull base recurrence of nasopharyngeal carcinoma after radiotherapy.

Tumor recurrence is a major cause of nasopharyngeal carcinoma (NPC) treatment failure. Diffusion-weighted imaging (DWI) is used for a variety of cancers, but few data are available for NPC.The aim of the study was to investigate the DWI features of recurrent NPC after radiotherapy and apparent diffusion coefficient (ADC) thresholds for the diagnosis of recurrent NPC.This was a retrospective study of 160 patients with NPC treated by radiotherapy at the Cancer Hospital affiliated to Guangxi Medical University from May 2012 to March 2015. The patients were divided into the local recurrence (n = 39), fibrosis (n = 51), clivus recurrence (n = 22), and clivus nonrecurrence (n = 48) groups. The patients underwent magnetic resonance imaging (MRI), enhanced MRI, and DWI. Receiver operating characteristics curves were used to determine sensitivity, specificity, and negative predictive values.ADC values were significantly different between the recurrence and fibrosis groups (P < .0001). Using ADC threshold values of 0.887 × 10 mm/s for local recurrence, the area under the curve (AUC) of DWI was 0.967 (87.2% sensitivity and 94.1% specificity), compared with 0.732 for routine MRI (71.8% sensitivity and 74.5% specificity) (P < .001). Using ADC threshold values of 1.018 × 10 mm/s for the diagnosis of clivus recurrent NPC, the AUC of DWI was 0.984 (95.5% sensitivity and 91.7% specificity) compared with 0.558 for routine MRI (63.6% sensitivity and 47.9% specificity) (P < .001).DWI has a higher diagnostic value for recurrent NPC than MRI. DWI can increase the diagnosis sensitivity and specificity of locally recurrent NPC.

Meta-analysis of diffusion-weighted magnetic resonance imaging in detecting prostate cancer.

PURPOSE: The objective of this study was to determine the diagnostic performance of quantitative diffusion-weighted magnetic resonance imaging in detection of prostate cancer. METHODS: A comprehensive search was performed for English articles published before May 2012 that fulfilled the following criteria: patients had histopathologically proved prostate cancer; diffusion-weighted imaging (DWI) was performed for the detection of prostate cancer, and data for calculating sensitivity and specificity were included. Methodological quality was assessed by using the quality assessment of diagnostic studies instrument. Publication bias analysis, homogeneity, inconsistency index, and threshold effect were performed by STATA version 12. RESULTS: Of 119 eligible studies, 12 with 1637 malignant and 4803 benign lesions were included. There was notable heterogeneity beyond threshold effect and publication bias. The sensitivity and specificity with 95% confidence interval (CI) estimates of DWI on a per-lesion basis were 77% (CI, 0.76-0.84) and 84% (CI, 0.78-0.89), respectively, and the area under the curve of summary receiver operating characteristic curve was 0.88 (CI, 0.85-0.90). The overall positive and negative likelihood ratios with 95% CI were 4.93 (3.39-7.17) and 0.278 (0.19-0.39), respectively. CONCLUSIONS: Quantitative DWI has a relative sensitivity and specificity to distinguish malignant from benign in prostate lesions. However, large-scale randomized control trials are necessary to assess its clinical value because of nonuniformed diffusion gradient b factor, diagnosis threshold, and small number of studies.

Apparent diffusion coefficient ratio between axillary lymph node with primary tumor to detect nodal metastasis in breast cancer patients.

PURPOSE: To evaluate the ratios of apparent diffusion coefficient (ADC) calculated from diffusion weighted imaging (DWI) between axillary lymph nodes with primary breast tumor lesions in the detection of axillary lymph nodes metastasis in breast cancer patients. MATERIALS AND METHODS: A total of 36 patients with breast tumors and their axillary lymph nodes were included in this study for MR image scan. The ADC values were calculated using DW-MR imaging software. The ADC values and the ADC ratios of axillary lymph nodes in patients with primary breast lesion were compared among benign and metastatic axillary lymph nodes. All the diagnosis were confirmed by histopathological examination. RESULTS: The mean ADC value of metastatic lymph nodes was significantly lower than those of benign lymph nodes (0.787 × 10(-3) mm(2)/s ± 0.145 versus 1.043 × 10(-3) mm(2)/s ± 0.257) (P < 0.05). In addition, ADC ratio of metastatic lymph nodes with breast lesion was significantly lower than those of benign lymph nodes with breast tumor lesions (0.986 ± 0.17 versus 1.375 ± 0.417) (P < 0.05). Once the ADC ratio was fixed at 0.889 × 10(-3) mm(2)/s, the sensitivity, specificity, and accuracy were 82.22%, 82.35% and 82.28%, respectively. The cutoff of ADC ratio was at 1.097 × 10(-3) mm(2)/s, the sensitivity, specificity, and accuracy can be up to 84.44%, 88.24%, and 86.08%. CONCLUSION: ADC value and ADC ratio could be used as a reliable parameter to detect the axillary lymph nodes metastasis in breast cancer patients, and ADC ratio has a higher accuracy.

The accuracy of computed tomographic perfusion in detecting recurrent nasopharyngeal carcinoma after radiation therapy.

OBJECTIVES: To assess the diagnostic accuracy of computed tomographic (CT) perfusion technique in discriminating recurrent nasopharyngeal carcinoma (NPC) after radiation therapy. METHODS: Forty-eight patients with a pathologic finding as reference standards were divided into 2 groups, recurrent and nonrecurrent NPCs. Perfusion parameters blood flow (BF), blood volume (BV), permeability surface (PS), and mean transit time were statistically analyzed. A receiver operating characteristic curve was used to study whether CT perfusion parameters could aid in detecting recurrent NPC. RESULTS: Blood flow, BV, and PS values between recurrent NPC (n = 27) and nonrecurrent NPC (n = 21) were 526.8 (168.1) versus 312.1 (214.4) mL/100 g per minute, 35.1 (23.6) versus 9.2 (8.0) (ml/100 g), and 53.4 (34.3) versus 17.6 (14.7) mL/100 g per minute, respectively. There was a significant difference between these 2 groups (P < 0.01). Mean transit time values in these 2 groups were 3.5 (2.0) versus 4.3 (2.7) seconds; there was no statistical difference. To optimize sensitivity and specificity, BF, BV, and PS threshold values for differentiating between recurrent and nonrecurrent NPCs were 537.20 mL/100 g per minute, 37.18 (ml/100 g), and 57.34 mL/100 g per minute, respectively. According to threshold values of BF, BV, and PS, sensitivity and specificity for distinguishing recurrent and nonrecurrent NPCs were 92.6% and 76.2%, 96.3% and 81%, and 81.5% and 61.9%, respectively. CONCLUSIONS: The CT perfusion technique may be helpful to find patients with recurrent NPC after radiation therapy.