As is known, liver metastases may often develop in GIS cancers, and the presence of metastasis of paramount importance in terms of treatment options and prognosis. As in many tumor groups, PET/CT is a globally accepted hybrid molecular imaging method in the diagnosis, staging and restaging of GIS cancers. 18FDG, a glucose analog, is the most commonly used radiopharmaceutical in PET imaging owing to its physical features and practicality in many tumor groups. There are numerous studies comparing 18FDG-PET/CT with radiological imaging modalities especially such as MRI in primary and metastatic liver tumors, and these studies have reported some limitations about 18FDG-PET/CT [13, 14].
The more specific radiopharmaceuticals are also needed in liver tumors as in most tumor subgroups in PET imaging. Recently, it is seen that the studies have been conducted to detect various cancers and metastases with 68GaDOTA-FAPI which is a novel PET radiopharmaceutical [15–17]. To our knowledge, our study is the first in the literature comparing 68GaDOTA-FAPI-PET/CT and 18FDG-PET/CT methods in detection of liver metastases of GIS cancers. Because of the 68GaDOTA-FAPI has been introduced as a new radiopharmaceutical in our clinic, this is a pilot study. On the other hand, although the number of the patients is low especially for tumor subgroups, data presented with total numbers of patients and lesions are sufficient for statistical significance.
According to our patient based results; a higher rate of cases was detected with 68GaDOTA-FAPI-PET/CT compared to those found with 18FDG-PET/CT modality and the difference was statistically significant. We believe that lower radiopharmaceutic uptake of liver parenchyma in 68GaDOTA-FAPI-PET/CT is one of the most important factors for this result. Although it was not exactly similar to our study in terms of patient groups and study design, in a study by Chen et al.  comparing both modalities, 68GaDOTA-FAPI-PET/CT was found to be superior in detection of the cases and lesions, similarly.
In addition to the advantage provided by 68GaDOTA-FAPI in terms of radiopharmaceutic uptake of liver parenchyma, previous studies have stated that 68GaDOTA-FAPI lacks physiological gastric and intestines radiopharmaceutic uptakes that are seen with 18FDG, and thus primary focus and peritoneal-mesenteric-omental metastases can be better detected in GIS cancers [15, 16, 18].
We believe that 68GaDOTA-FAPI-PET/CT may be preferred instead of 18FDG-PET/CT in GIS cancers in the near future, due to its’ superiorities stated in the mentioned studies and its success in detecting liver metastases as demonstrated in our study.
While a significantly higher number of lesions were detected with 68GaDOTA-FAPI-PET/CT compared to 18FDG-PET/CT in total lesions number, no statistically significant difference was found for lesion numbers on each-one patient.
Although histopathological confirmation and distinguishing of the differentiation status could not be made in all lesions, as stated before this situtation can be explained with better detection of the lesions because of low liver parenchymal radiopharmaceutical activity. Furthermore, in addition to the high radiopharmaceutic uptake of liver parenchyma in 18FDG-PET/CT imaging, especially small-sized lesions might have not been distinguished due to partial volume effect. Other conditions that may explain this results are other processes that may cause false positive and negative findings in 18FDG-PET/CT imaging.
On the other hand, some studies have reported that processes related to inflammation may also cause false positive findings in 68GaDOTA-FAPI-PET/CT imaging [18–20]. In the considering of the possible causes stated in these studies, cirrhotic patients were excluded from our study in order to minimize the processes that could resulted in inflammation and fibrosis in the liver parenchyma. And also, the decision for positive-negative lesions on the both PET/CT imaging was made taken into account mlr values in addition of SUVmax values to optimize inflammation that could be resulted from hepatosteatosis. In our study, it was found that false positivity in 1 patient and false negativity in 1 patient on 68GaDOTA-FAPI-PET/CT.
Unfortunately, since majority of the metastatic lesions could not be confirmed histopathologically and studies in the literature on this subjects have just started to be published, we could not made a clear interpretation about the other possible mechanisms that might have caused false positive-negative results in 68GaDOTA-FAPI-PET/CT. Therefore, further studies are needed on this subject in which the lesions are confirmed histopathologically.
In the current study, SUVmax values of the lesions were also found to be in 68Ga-FAPI-PET-CT higher than 18FDG-PET/CT, and these results are consistent with the results of Chen et al. . But, no statistically significant difference was found between the two PET/CT imaging modalities in terms of the SUVmax of the lesions in tumor subgroups.
On the other hand, statistically significant difference was found in favor of 68Ga-FAPI-PET-CT for mlr values in all subgroups. For further studies that will compare both PET/CT imaging methods, we think that mlr would provide a significant contribution for the detection of liver lesions, and will be useful especially in the cases where making a decision based on SUVmax values is challenging.
The main limitations in our study can be listed as; the number of cases was relatively small especially in tumor subgroups in spite of the sufficient total number of lesions, it was not designed as a prospective randomized study, and not all lesions were histopathologically confirmed.
In conclusion; despite the main limiting factors, our study showed that 68GaDOTA-FAPI-PET/CT is a superior imaging modality over 18FDG-PET/CT in detection of liver metastases of GIS cancers, and in current conditions it may be a complementary method for 18FDG-PET/CT. We believe that 68GaDOTA-FAPI-PET/CT will be a more practical method in the diagnosis, staging and restaging of GIS cancers because of both its success in detection of liver metastases and the advantages that it provides in visualization of the primary lesions and intra-abdominal metastases, and will take place in diagnosis and follow-up algorithm in line with the results of further studies to be conducted in this field.