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Limitations of Fluorine 18 Fluoromisonidazole in Assessing Treatment-induced Tissue Hypoxia after Transcatheter Arterial Embolization of Hepatocellular Carcinoma: A Prospective Pilot Study.

ABSTRACT: Purpose To determine the variance and correlation with tumor viability of fluorine 18 (¹⁸F) fluoromisonidazole (FMISO) uptake in hepatocellular carcinoma (HCC) prior to and after embolization treatment. Materials and Methods In this single-arm, single-center, prospective pilot study between September 2016 and March 2017, participants with at least one tumor measuring 1.5 cm or larger with imaging or histologic findings diagnostic for HCC were enrolled (five men; mean age, 68 years; age range, 61-76 years). Participants underwent ¹⁸F-FMISO PET/CT before and after bland embolization of HCC. A tumor-to-liver ratio (TLR) was calculated by using standardized uptake values of tumor and liver. The difference in mean TLR before and after treatment was compared by using a Wilcoxon rank sum test, and correlation between TLR and tumor viability was assessed by using the Spearman rank correlation coefficient. Results Four participants with five tumors were included in the final analysis. The median tumor diameter was 3.2 cm (IQR, 3.0-3.9 cm). The median TLR before treatment was 0.97 (IQR, 0.88-0.98), with a variance of 0.02, and the median TLR after treatment was 0.85 (IQR, 0.79-1), with a variance of 0.01; both findings indicate a narrow range of ¹⁸F-FMISO uptake in HCC. The Spearman rank correlation coefficient was 0.87, indicating a high correlation between change in TLR and nonviable tumor. Conclusion Although there was a correlation between change in TLR and response to treatment, the low signal-to-noise ratio of ¹⁸F-FMISO in the liver limited its use in HCC. Keywords: Molecular Imaging-Clinical Translation, Embolization, Abdomen/Gastrointestinal, Liver Clinical trial registration no. NCT02695628 © RSNA, 2022.

SUBMITTER: Shah RP

PROVIDER: S-EPMC9152693 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Limitations of Fluorine 18 Fluoromisonidazole in Assessing Treatment-induced Tissue Hypoxia after Transcatheter Arterial Embolization of Hepatocellular Carcinoma: A Prospective Pilot Study.

Shah Rajesh P RP Laeseke Paul F PF Shin Lewis K LK Chin Frederick T FT Kothary Nishita N Segall George M GM

Radiology. Imaging cancer 20220501 3

Purpose To determine the variance and correlation with tumor viability of fluorine 18 (<sup>18</sup>F) fluoromisonidazole (FMISO) uptake in hepatocellular carcinoma (HCC) prior to and after embolization treatment. Materials and Methods In this single-arm, single-center, prospective pilot study between September 2016 and March 2017, participants with at least one tumor measuring 1.5 cm or larger with imaging or histologic findings diagnostic for HCC were enrolled (five men; mean age, 68 years; ag ...[more]

PMID: 35485937

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Project description:PurposeTranscatheter arterial embolization or transcatheter arterial chemoembolization has become a critical therapy for unresectable hepatocarcinoma. Although hypoxia caused by embolization can induce apoptosis and necrosis of the majority of tumor cells, a small proportion of cells can survive with hypoxia and chemotherapy resistance. HIF-1α induced by hypoxia is the key factor rendering surviving tumor cells invasive and metastatic properties. Thus, we generated a synthetic hypoxia-replicative oncolytic adenovirus (HYAD) expecting to further eliminate the surviving tumor cells, which expressed HIF-1α.Materials and methodsIn our study, we detected protein expression, proliferation, apoptosis, and necrosis of hepatic tumor cell line when infected with HYAD under hypoxia and normoxia. And we constructed VX2 hepatic cancer rabbit models to explore the therapeutic effect of transcatheter arterial embolization combined with HYAD perfusion under digital subtraction angiography. Inhibition of tumor growth and invasion was detected by histopathological examination and contrast-enhanced CT scan.ResultsExperiments in vitro verified that HYAD expressed and replicated along with HIF-1α expression or hypoxia. Compared with wild adenovirus type 5 (WT), HYAD expressed much more under hypoxia, which was the main principle of HYAD killing surviving tumor cells posttransarterial embolization. In vivo experiment of VX2 models, HYAD perfusion combined with polyvinyl alcohol (PVA) embolization achieved the highest expression quantity and the longest expression duration compared with simple HYAD perfusion, WT perfusion combined with PVA embolization, and simple WT perfusion. Because adenovirus expression protein E1A had the properties of promoting apoptosis, inhibiting invasion, and inhibiting metastasis, HYAD perfusion combined with PVA embolization group efficiently repressed tumor growth and intrahepatic metastases compared to other processing groups.ConclusionHYAD can overcome the hypoxic tumor microenvironment postembolization and target the surviving tumor cells with specificity. In turn, HYAD perfusion combined with PVA embolization can bring out the best effect in each other.

Dataset Information

Limitations of Fluorine 18 Fluoromisonidazole in Assessing Treatment-induced Tissue Hypoxia after Transcatheter Arterial Embolization of Hepatocellular Carcinoma: A Prospective Pilot Study.

Publications

Limitations of Fluorine 18 Fluoromisonidazole in Assessing Treatment-induced Tissue Hypoxia after Transcatheter Arterial Embolization of Hepatocellular Carcinoma: A Prospective Pilot Study.

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