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.

Keywords: Abdomen/Gastrointestinal; Embolization; Liver; Molecular Imaging-Clinical Translation.

Conflict of interest statement

Disclosures of conflicts of interest: R.P.S. Funding from Stanford University Department of Radiology; grants from Merit Medical Healthcore-NERI, Lucence Health; consulting fees from Intuitive Surgical, Genentech, Artio Medical Histosonics; participation on a Data Safety Monitoring Board or Advisory Board from Histosonics; leadership or fiduciary role in the Society of Interventional Radiology; investor in Sky Creek Capital Healthcare Fund. P.F.L. Grants from Siemens Medical, Histosonics; consulting fees from Johnson and Johnson, Ethicon, Neuwave, Histosonics, Elucent Medical; stock or stock options from Histosonics, Elucent Medical, McGinley Orthopedic Innovations. L.K.S. No relevant relationships. F.T.C. Grants, as follows: R01 CA238686-01A1 Rosenthal & Chin (Co-PIs) 09/01/2019 – 08/31/2021, R21 HD095319 (PI: Chin) 05/01/2019 – 04/30/2021, R01 AG061120-01A1 (Co-Investigator: Chin) 03/01/2019 – 12/31/2023, R21AG058859 (Co-Investigator: Chin) 03/15/2018 – 02/28/2021, 1RF1MH11425201 (Co-Investigator: Chin) 07/19/2017 – 07/18/2021; R01 HD084214 (PI: Chin) 09/22/2014 – 11/30/2020, GE Healthcare Research Grant (Co-Investigator: Chin) 09/04/2016 – 09/30/2020, Stanford SPARK Project Seed Grant Yoon and Chin (Co-PIs) 06/01/2018 – 12/31/2020; leadership or fiduciary role in other board, society, committee, or advocacy group, as follows: GE Healthcare PET Radiopharmacy User Forum Meeting at 2019 Annual Society of Nuclear Medicine and Molecular Imaging, Anaheim, CA – Chairperson; iQ PHARMA, International Expert Panel, iQ PHARMA PET NETWORK Meeting held during ALASBIMN Congress on November 13, 2019 in Lima, Peru; ALASBIMN (aka The Latin American Association of Societies of Biology and Nuclear Medicine). Stock or stock options in Ground Fluor Pharma. N.K. Research funding from Echopixel; consulting fees from Quantum Surgical; stock or stock options from Neptune medical. G.M.S. No relevant relationships.

Figures

Figure 1:

Participant study flowchart. Participants were screened in the interventional radiology clinic after consent was obtained and underwent fluorine 18 (18F) fluoromisonidazole (FMISO) PET/CT imaging if criteria were met.

Figure 2:

Tumor-to-liver ratio (TLR) plotted for tumor viability before treatment versus after treatment. The TLR after embolization was higher for nonviable tumors than for viable tumors.

Figure 3:

Fluorine 18 (18F) fluoromisonidazole (FMISO) uptake in the liver before and after embolization for participant 1 (66-year-old man with hepatocellular carcinoma) with residual tumor after treatment.(A) Axial contrast-enhanced CT image acquired before embolization shows enhancing tumor (arrow) in segments 5/8.(B) Axial 18F-FMISO PET/CT image acquired before embolization shows uptake in the tumor (arrow) similar to that of liver parenchyma, with yellow and red areas indicating increased uptake.(C) Axial 18F-FMISO PET/CT image acquired after embolization shows minimal uptake in the tumor (arrow).(D) Axial contrast-enhanced CT image acquired 2 months after embolization shows enhancing viable tumor (arrow).

Figure 4:

Fluorine 18 (18F) fluoromisonidazole (FMISO) uptake in the liver before and after embolization in participant 3, a 65-year-old man with hepatocellular carcinoma and nonviable tumor after treatment.(A) Axial contrast-enhanced CT image acquired before embolization shows a segment-7 enhancing tumor (arrow). (B)Axial 18F-FMISO PET/CT image acquired before embolization shows uptake in the tumor (arrow) similar to that of liver parenchyma, with yellow and red areas indicating increased uptake. (C)Axial 18F-FMISO PET/CT image acquired after embolization shows continued uptake in the tumor (arrow). Note the focal contrast retention in the tumor from retained embolic particles. (D)Axial contrast-enhanced CT image acquired at 2 months after embolization shows necrosis with no viable tumor (arrow).