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Afyouni et al. Hepatoma Res 2023;9:28 https://dx.doi.org/10.20517/2394-5079.2023.29 Page 7 of 14

More recently, novel ligands have been developed alongside the PET technique. Of note, in contrast to
cancer-associated fibroblasts, normal human tissues have very little fibroblast activation protein (FAP)
[70]
expression . PET can image this pathophysiological process using the new ligand “fibroblast activation
protein inhibitor (FAPI)” attached to fluorine-18 or gallium-68. FAPI PET is safe and has outperformed
FDG in early clinical trials . In a recent study, Veldhuijzen van Zanten et al. compared FAPI PET to FDG
[71]
PET, CECT, and MRI to stage pancreatic, gastric, and cholangiocarcinoma. While initial studies have
suggested that FAPI PET may outperform other conventional diagnostic methods, few investigations have
been done, and more data are needed. FAPI has theranostic potential since its ligand can bind to diagnostic
or therapeutic radioisotopes .
[72]

THE ROLE OF DIAGNOSTIC RADIOLOGY IN MONITORING THE TREATMENT RESPONSE
Conventional tumor response criteria proposed by the World Health Organization WHO, the response
evaluation criteria in solid tumors (RECIST), the modified RECIST (mRECIST), and the European
Association for the Study of the Liver all use a decrease in tumor size or enhancement as an indicator of
[74]
[73]
tumor response . However, these methods may not be very reliable or very reproducible . In addition, it
can be difficult to use mRECIST and European Association for the Study of the Liver criteria because of the
hypovascular character of ICC caused by its fibrous stroma .
[75]
The most recent innovation in functional MRI techniques has enabled quantitative assessment of cellular
integrity. Data have suggested a potential value of functional MRI characteristics to determine the efficacy
of local-regional therapies, particularly intraarterial therapies, for various hepatic malignancies .
[3]

Multiparametric MRI, which includes T2-weighted imaging, DWI, DCE-MRI, and spectroscopic imaging, is
more sensitive to cellular changes throughout treatment, allowing for a more accurate description of the
therapeutic response and prognosis. Using these methods, it is possible to detect early cellular damage in
tumors before any change in size . Increased cell membrane permeability caused by cellular necrosis
[76]
allows water molecules to circulate freely, hence elevating ADC values .
[37]
Monitoring the response to TACE
A more precise and tailored patient selection to TACE would be possible with the help of forecasting
therapeutic outcomes prior to this therapy and its probable efficacy. In this regard, Halappa et al. evaluated
volumetric changes in ADC and contrast enhancement on MRI in ICC patients undergoing TACE.
According to their results, patients with a percentage tumor volume increase in ADC of 45% or greater and
60% or greater above the threshold level of 1.60 × 10 mm /sec had a favorable response to therapy and
-3
2
improved survival .
[76]
Recently, Pandey et al. performed a study to evaluate the efficacy of MRI-extracted features for assessment
of response to TACE. They reported that changes in volumetric ADC can predict the outcome among these
[77]
patients .
In another study, Pandey et al. reported that certain characteristics observed in baseline MRI scans can
serve as predictors of higher survival rates in patients with ICC, independent of clinical factors. These
predictors include a low ADC, indicating a smaller viable tumor volume and a higher level of necrosis and
cell membrane damage. These characteristics suggest a more aggressive tumor phenotype, as indicated by
the hypoxic environment and resistance to systemic therapy .
[78]