Molecular MRI of the Immuno-Metabolic Interplay in a Rabbit Liver Tumor Model: A Biomarker for Resistance Mechanisms in Tumor-targeted Therapy?

Savic, Lynn Jeanette; Doemel, Luzie A.; Schobert, Isabel; Montgomery, Ruth R.; Joshi, Nikhil S.; Walsh, John J.; Santana, Jessica G.; Pekurovsky, Vasily; Zhang, Xuchen; Lin, MingDe; Adam, Lucas C.; Boustani, A.; Duncan, James S.; Leng, Lin; Bucala, Richard John; Goldberg, S. Nahum; Hyder, Fahmeed; Coman, Daniel; Chapiro, Julius

doi:10.1148/radiol.2020200373

Cited by 19 publications

(15 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A total of 28 adult male Japanese white rabbits weighing 2.5 to 3.0 kg were involved ( 19 , 20 ). A tumor-bearing rabbit was used to develop the tumor masses for implantation.…”

Section: Methodsmentioning

confidence: 99%

Early Assessment of Response to Radiofrequency Ablation With CT Perfusion Imaging in Rabbit VX2 Liver Tumor Model

et al. 2021

View full text Add to dashboard Cite

ObjectivesTo discriminate viable tumors from benign periablational enhancement (BPE) in early stage after radiofrequency ablation (RFA) is a major confounding problem. The goal of this study is to evaluate quantitative assessment and diagnostic value of CT perfusion between viable tumors and BPE after RFA in the rabbit liver VX2 tumor model, with pathological results as the standard.MethodsTwenty-eight VX2 liver tumors were treated with RFA, on days 1, 3, 7, and 14, seven rabbits were randomly chosen for CT perfusion and performed pathology examinations immediately. The perfusion parameters along with the profile of time-density curves (TDCs) and pseudo-color images of the parameters were observed in both BPE and viable tumors, then compared with the pathology results. The perfusion parameters included blood flow (BF), blood volume (BV), time to peak (TTP), permeability (P), arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic perfusion index (HPI).ResultsA total of 26/28 rabbits successfully underwent CT perfusion, while 6/26 lesions were confirmed to be viable tumors. The TDCs of BPE were mainly speed-up platform curves (15/26), while the viable tumors showed mainly speed-up speed-down (3/6) and speed-up platform (2/6) curves. The PVP values were significantly higher, and the HPI values were significantly lower for BPE at all time points than viable tumors (P < 0.05). Both of PVP value and HPI value have high efficiency for the differential diagnosis of the viable tumors and BPE at each time point. These characteristics of CT perfusion parameters were consistent with pathological changes.ConclusionsThe TDCs, PVP and HPI have the potential to indicate BPE and viable tumors effectively early after RFA treatment, the results were highly consistent with pathology. CT perfusion has advantages with great efficacy in monitoring the therapeutic effect early after RFA treatment.

show abstract

“…A total of 28 adult male Japanese white rabbits weighing 2.5 to 3.0 kg were involved ( 19 , 20 ). A tumor-bearing rabbit was used to develop the tumor masses for implantation.…”

Section: Methodsmentioning

confidence: 99%

Early Assessment of Response to Radiofrequency Ablation With CT Perfusion Imaging in Rabbit VX2 Liver Tumor Model

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Drinking water and food were available ad libitum. Twelve rabbits (experimental group) underwent implantation of VX2 tumor chunks in the left liver lobe as described in detail in previous studies 37 – 40 . Briefly, a freshly prepared suspension of cells derived from an established VX2 tumor cell line was injected in the muscle of the hind thigh of four donor rabbits (donor group).…”

Section: Methodsmentioning

confidence: 99%

Elastin-specific MRI of extracellular matrix-remodelling following hepatic radiofrequency-ablation in a VX2 liver tumor model

Collettini

Reimann

Brangsch

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

Hepatic radiofrequency ablation (RFA) induces a drastic alteration of the biomechanical environment in the peritumoral liver tissue. The resulting increase in matrix stiffness has been shown to significantly influence carcinogenesis and cancer progression after focal RF ablation. To investigate the potential of an elastin-specific MR agent (ESMA) for the assessment of extracellular matrix (ECM) remodeling in the periablational rim following RFA in a VX2 rabbit liver tumor-model, twelve New-Zealand-White-rabbits were implanted in the left liver lobe with VX2 tumor chunks from donor animals. RFA of tumors was performed using a perfused RF needle-applicator with a mean tip temperature of 70 °C. Animals were randomized into four groups for MR imaging and scanned at four different time points following RFA (week 0 [baseline], week 1, week 2 and week 3 after RFA), followed by sacrifice and histopathological analysis. ESMA-enhanced MR imaging was used to assess ECM remodeling. Gadobutrol was used as a third-space control agent. Molecular MR imaging using an elastin-specific probe demonstrated a progressive increase in contrast-to-noise ratio (CNR) (week 3: ESMA: 28.1 ± 6.0; gadobutrol: 3.5 ± 2.0), enabling non-invasive imaging of the peritumoral zone with high spatial-resolution, and accurate assessment of elastin deposition in the periablational rim. In vivo CNR correlated with ex vivo histomorphometry (ElasticaVanGiesson-stain, y = 1.2x − 1.8, R2 = 0.89, p < 0.05) and gadolinium concentrations at inductively coupled mass spectroscopy (ICP-MS, y = 0.04x + 1.2, R2 = 0.95, p < 0.05). Laser-ICP-MS confirmed colocalization of elastin-specific probe with elastic fibers. Following thermal ablation, molecular imaging using an elastin-specific MR probe is feasible and provides a quantifiable biomarker for the assessment of the ablation-induced remodeling of the ECM in the periablational rim.

show abstract

“…( 67 ) A study demonstrated that specific gadolinium 160‐labeled anti‐human leukocyte antigen–DR isotope antibodies (160Gd‐HLA‐DR antibodies) and superparamagnetic iron oxide nanoparticles (SPIONs) showed curvilinear peritumoral distribution on MRI scans in a VX2 rabbit liver tumor model, corresponding to APCs and iron deposits in macrophages, respectively. ( 68 ) In addition, glypican‐3 (GPC3) is a carcinoembryonic antigen that is an ideal target for anticancer immunotherapy against HCC. A study showed that patients with GPC3‐expressing HCCs exhibited an increase in GPC3‐specific cytotoxic T lymphocytes after RFA or TACE, whereas none of the patients did after surgical resection.…”

Section: Molecular Imaging Of Tme After Lrt In Hccmentioning

confidence: 99%

Molecular Imaging of Tumor Microenvironment to Assess the Effects of Locoregional Treatment for Hepatocellular Carcinoma

Chen

et al. 2021

Hepatol Commun

View full text Add to dashboard Cite

Liver cancer is one of the leading causes of cancer deaths worldwide. Among all primary liver cancers, hepatocellular carcinoma (HCC) is the most common type, representing 75%‐85% of all primary liver cancer cases. Median survival following diagnosis of HCC is approximately 6 to 20 months due to late diagnosis in its course and few effective treatment options. Interventional therapy with minimal invasiveness is recognized as a promising treatment for HCC. However, due to the heterogeneity of HCC and the complexity of the tumor microenvironment, the long‐term efficacy of treatment for HCC remains a challenge in the clinic. Tumor microenvironment, including factors such as hypoxia, angiogenesis, low extracellular pH, interstitial fluid pressure, aerobic glycolysis, and various immune responses, has emerged as a key contributor to tumor residual and progression after locoregional treatment for HCC. New approaches to noninvasively assess the treatment response and assist in the clinical decision‐making process are therefore urgently needed. Molecular imaging tools enabling such an assessment may significantly advance clinical practice by allowing real‐time optimization of treatment protocols for the individual patient. This review discusses recent advances in the application of molecular imaging technologies for noninvasively assessing changes occurring in the microenvironment of HCC after locoregional treatment.

show abstract

Molecular MRI of the Immuno-Metabolic Interplay in a Rabbit Liver Tumor Model: A Biomarker for Resistance Mechanisms in Tumor-targeted Therapy?

Cited by 19 publications

References 35 publications

Early Assessment of Response to Radiofrequency Ablation With CT Perfusion Imaging in Rabbit VX2 Liver Tumor Model

Early Assessment of Response to Radiofrequency Ablation With CT Perfusion Imaging in Rabbit VX2 Liver Tumor Model

Elastin-specific MRI of extracellular matrix-remodelling following hepatic radiofrequency-ablation in a VX2 liver tumor model

Molecular Imaging of Tumor Microenvironment to Assess the Effects of Locoregional Treatment for Hepatocellular Carcinoma

Contact Info

Product

Resources

About