New PET Tracer Outshines Standard FDG Scan in Spotting Cancer Spread to the Liver

A novel molecular imaging agent has delivered a striking performance against the long-reigning standard of cancer imaging. In a head-to-head comparison of gallium-68 labeled FAPI-04 and fluorine-18 fluorodeoxyglucose PET/CT, researchers found that the newer tracer detected liver metastases across a wide range of malignant tumors with significantly higher sensitivity and accuracy. The findings, drawn from one of the largest directly comparative datasets published to date, suggest that FAPI-based imaging could reshape how clinicians hunt for cancer that has spread to the liver, the organ most commonly colonized by metastatic disease.

The stakes are high. The liver is among the most frequent sites of distant spread in malignant tumors, and the number of patients with liver metastases substantially exceeds the number diagnosed with primary liver cancer. Prognosis is poor: one-year overall survival for patients with liver metastases has been reported at roughly 15 percent, compared with 24 percent for patients without such spread. Yet early and precise detection matters enormously, because options ranging from surgical resection and ablation to stereotactic radiotherapy and transarterial therapies can be curative or life-extending in selected patients. In colorectal cancer, for example, resection of limited liver metastases can push five-year survival to between 47 and 60 percent, and some patients with non-colorectal liver metastases also benefit from surgery. Accurate imaging is the gateway to those decisions.

The study, conducted at Fudan University Shanghai Cancer Center and published in Holistic Integrative Oncology, enrolled 76 patients between May 2020 and April 2023 who underwent both scans within one week. The cohort spanned 19 different malignant tumor types, comprising 65 patients with carcinomas and 11 with sarcomas, and a total of 189 liver lesions, of which 173 were ultimately confirmed as metastases through at least three months of clinical and imaging follow-up. Two experienced nuclear medicine physicians, blinded to clinical data and follow-up results, independently evaluated the images using a standardized visual scoring system supplemented by quantitative measurements.

The technical logic behind the comparison hinges on the biology of each tracer. Fluorodeoxyglucose, or FDG, is a glucose analogue that accumulates in cells with high glycolytic activity, the metabolic hallmark of many cancers. But FDG is relatively nonspecific: all living cells consume glucose, and the liver’s own background uptake is brisk, which can mask malignant lesions and inflate the false-negative rate. FAPI-04, by contrast, targets fibroblast activation protein, or FAP, a marker abundantly expressed by cancer-associated fibroblasts in the tumor stroma of a broad spectrum of malignancies. Crucially for liver imaging, FAP expression in normal hepatic parenchyma is low, producing a dark, quiet background against which bright metastatic lesions stand out with high contrast.

The results were emphatic. Across all 76 patients, the sensitivity of gallium-68 FAPI-04 PET/CT for detecting liver metastases was 94.80 percent, compared with 69.94 percent for FDG PET/CT, a difference that was highly statistically significant. Accuracy followed the same pattern, at 91.53 percent versus 70.37 percent. In the carcinoma subgroup the gap widened further: sensitivity of 97.87 percent versus 73.05 percent, and accuracy of 96.05 percent versus 74.34 percent. Even in the smaller sarcoma group, FAPI-04 achieved significantly higher sensitivity, 81.25 percent versus 56.25 percent, although accuracy did not reach statistical significance in that subset. Specificity did not differ significantly between the two tracers in any group.

Quantitative uptake measurements reinforced the visual findings. The researchers compared the maximum standardized uptake value, or SUVmax, of each lesion with the mean uptake of normal liver tissue to derive the tumor-to-background ratio, or TBR. Normal liver background activity was markedly lower with FAPI-04 than with FDG, with a mean SUV of 1.10 versus 2.61. Although overall SUVmax of metastases did not differ significantly across the whole cohort, the median TBR for FAPI-04 was more than double that of FDG, 4.60 versus 1.67, and in carcinomas both SUVmax and TBR were significantly higher for FAPI-04. In essence, even when lesion signal was similar, the quieter liver background made FAPI-04 lesions far easier to see.

The clinical consequences of that contrast were tangible. In ten patients, liver metastases were clearly positive on FAPI-04 PET/CT yet invisible to FDG PET/CT. Because distant spread determines the M stage of the TNM classification, detecting these lesions changed the staging of those patients and could alter treatment planning, from surgical candidacy and radiotherapy target delineation to systemic therapy decisions. For patients with limited, oligometastatic liver disease, more aggressive local interventions such as resection, stereotactic ablative radiotherapy, or microwave ablation may be appropriate, but only if all sites of disease are reliably identified first.

The study’s authors contextualized their findings against existing imaging standards. Magnetic resonance imaging with diffusion-weighted sequences and gadoxetic acid contrast remains the reference method for characterizing liver lesions, with pooled sensitivity of about 95 percent and specificity of about 82 percent in meta-analysis. Notably, the carcinoma subgroup performance of FAPI-04 PET/CT in this study approached those figures, making it a credible alternative for patients who cannot receive gadolinium contrast because of renal impairment or allergy. Prior smaller studies in gastrointestinal cancers and mixed tumor populations had already hinted at FAPI’s advantage, with sensitivities of 96.6 to 98.2 percent, but limited sample sizes and narrow tumor spectra left the picture incomplete. The Shanghai team’s broader cohort and explicit carcinoma-versus-sarcoma stratification add statistical weight and biological nuance.

Why did FAPI-04 perform less decisively in sarcomas? The authors point to fundamental differences in tumor origin. Carcinomas arise from epithelial tissue and typically provoke a robust stromal reaction rich in FAP-expressing fibroblasts, whereas sarcomas of mesenchymal origin display heterogeneous and often lower stromal FAP expression. That heterogeneity likely explains both the lower accuracy of 72.97 percent in sarcoma and the absence of a significant SUVmax advantage, even though the tumor-to-background ratio still favored FAPI-04 significantly. The modest specificity observed for both tracers also has recognized culprits: benign lesions such as angiomyolipoma and focal nodular hyperplasia can take up FAPI, inflammatory focal liver lesions can be FAPI-avid, and fibrotic nodules from chronic hepatitis, alcoholic liver disease, or fatty liver disease may trap the tracer, since fibroblast activation protein is a hallmark of activated hepatic stellate cells in fibrosis.

The researchers are careful to frame their conclusions as preliminary. The analysis was retrospective, most metastases were confirmed by follow-up rather than biopsy, the cohort came from a single center, and the sarcoma subgroup was small enough to invite statistical bias. Only the lesion most suspicious for malignancy per patient was generally included, which may have flattered both scanners’ performance. Still, the magnitude and consistency of FAPI-04’s advantage in carcinoma metastases, the modality where detection most often determines resectability, make a compelling case for larger prospective trials, including direct comparisons with liver MRI. If validated, a routine switch in tracer for patients at risk of hepatic spread would be a rare and consequential upgrade in an imaging workhorse that has remained largely unchanged for decades.

Subject of Research: Comparative diagnostic performance of 68Ga-FAPI-04 and 18F-FDG PET/CT imaging for detecting liver metastases from malignant tumors.

Article Title: Head-to-head comparison of the detection performance and tumor uptake of 68Ga-FAPI-04 and 18F-FDG PET/CT in liver metastases from malignant tumors of different types

Article References: Ma, G., Liu, C., Qi, M., Li, J., & Song, S. (2026). Head-to-head comparison of the detection performance and tumor uptake of 68Ga-FAPI-04 and 18F-FDG PET/CT in liver metastases from malignant tumors of different types. Holistic Integrative Oncology, 5(1), Article 74. https://doi.org/10.1007/s44178-026-00295-4

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00295-4

Keywords: 68Ga-FAPI-04, 18F-FDG, PET/CT, liver metastases, molecular imaging, fibroblast activation protein, carcinoma, sarcoma, SUVmax, tumor-to-background ratio, cancer staging, nuclear medicine