The study, led by Xiaoli Gou and colleagues working across the Xi’an Hospital of Traditional Chinese Medicine and the First Affiliated Hospital of Air Force Medical University in Xi’an, China, enrolled 81 patients with confirmed rectal cancer. Every patient underwent a whole-abdominal MRI scan and a whole-body ⁶⁸Ga-FAPI-04 PET/CT scan before surgery, allowing the researchers to compare both modalities against the pathological gold standard obtained from the resected tissue. The work was a single-center retrospective cohort study, meaning the team looked back at imaging and pathology records rather than randomizing patients prospectively.

The molecular scan at the heart of the study uses a radioactive isotope of gallium-68 attached to a fibroblast activation protein inhibitor, or FAPI. Fibroblast activation protein is expressed at high levels by cancer-associated fibroblasts, the stromal cells that surround and support many solid tumors. Because the tracer homes in on this protein rather than on glucose metabolism, as the more common fluorine-18 fluorodeoxyglucose tracer does, FAPI PET can sometimes light up tumors with higher contrast and lower background signal, particularly in tissues where FDG uptake is normally confusing.

When the researchers compared the two modalities for T staging, which describes how deeply the primary tumor has invaded the rectal wall, MRI came out ahead. For assessing T2-stage tumors, MRI achieved a specificity of 85.25 percent and an overall accuracy of 86.42 percent, while ⁶⁸Ga-FAPI-04 PET/CT reached only 59.02 percent specificity and 62.96 percent accuracy. The pattern repeated for T3 staging, where MRI delivered an overall accuracy of 83.95 percent compared with 69.14 percent for PET/CT. All of these intergroup differences were statistically significant, with P values below 0.001, indicating that the gaps were unlikely to be due to chance alone.

The picture flipped when the team turned to nodal staging. For identifying N1 disease, meaning cancer spread to regional lymph nodes, ⁶⁸Ga-FAPI-04 PET/CT showed a specificity of 87.72 percent and an accuracy of 80.25 percent, compared with 73.68 percent and 62.96 percent respectively for MRI. These differences also reached statistical significance, with P values of 0.039 for specificity and 0.004 for accuracy. The result aligns with the known limitations of MRI for lymph node characterization, which relies on morphological criteria such as size and border irregularity that cannot reliably distinguish reactive from malignant nodes.

The advantage of the molecular scan extended beyond the pelvis. Within the overlapping abdominopelvic scanning range shared by both protocols, ⁶⁸Ga-FAPI-04 PET/CT identified six metastatic lesions compared with three for MRI. More strikingly, the PET/CT scan detected 14 metastatic lesions located outside the abdominopelvic coverage area that were invisible on MRI, which in this study was limited to the abdomen and pelvis. Because the whole-body PET/CT scan surveys the entire torso, it can catch distant deposits in the chest, bones, or elsewhere that a regional MRI protocol would never image. For the statistical comparison of M staging, the researchers only compared detection performance within the overlapping coverage zone, describing lesions outside it qualitatively to avoid biasing the analysis.

Beyond the visual read, the team extracted five quantitative metabolic parameters from the PET scans: maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume, total lesion uptake, and tumor-to-background ratio. All five parameters showed distinct values across different T categories, with P values below 0.001. Total lesion uptake, or TLU, which combines the intensity of tracer uptake with the volume of metabolically active tumor, showed the strongest positive linear association with T stage, with a Spearman correlation coefficient of 0.752 and a P value below 0.001. Binary logistic regression analysis preliminarily indicated a statistical correlation between TLU and T3 disease status.

The diagnostic power of these numbers was then tested formally. When the task was to distinguish T1 and T2 low-stage tumors from T3 lesions, TLU alone generated an area under the receiver operating characteristic curve, or AUC, of 0.889. At its optimal threshold of 64.354, TLU provided a sensitivity of 81.00 percent and a specificity of 86.20 percent. Combined parameter groups performed even better: SUVmax plus TLU produced an AUC of 0.883, while the combination of the apparent diffusion coefficient from MRI and TLU reached an AUC of 0.935. At their respective optimal cut-off values, both combined groups yielded a sensitivity of 78.60 percent and a specificity of 93.10 percent. Decision curve analysis, which quantifies the net clinical benefit of a test across a range of probability thresholds, indicated that the ADC plus TLU combination provided the maximum net benefit throughout the 0 to 50 percent probability threshold interval.

The authors conclude that MRI remains the primary imaging modality for local T-staging evaluation, especially for T2 and T3 rectal lesions, while ⁶⁸Ga-FAPI-04 PET/CT achieves superior diagnostic performance in N1 nodal staging and in the identification of distant metastases. The quantitative indicators derived from the PET scan, particularly TLU and the combined parameter groups, preliminarily indicate favorable diagnostic ability and carry potential auxiliary value to assist MRI in differentiating distinct T-stage subgroups. In practical terms, the two technologies are not competitors but complements, each covering the other’s blind spots.

Several caveats temper the enthusiasm. The study was retrospective and conducted at a single center, so the findings require prospective validation in larger, multi-institution cohorts before they can change clinical guidelines. The comparison of M staging was restricted to the overlapping scan range, and lesions detected outside it were described only qualitatively. The sample of 81 patients, while sufficient for the statistical tests performed, limits the precision of subgroup estimates. Nevertheless, the head-to-head design, the pathological gold standard, and the integration of quantitative PET metrics with MRI-derived diffusion parameters offer a template for how molecular imaging and anatomical imaging might be woven together into a more accurate preoperative roadmap for rectal cancer surgery.

Subject of Research: Oncology

Article Title: Comparison of diagnostic performance between MRI and ⁶⁸Ga-FAPI-04 PET/CT for stratified preoperative TNM staging of rectal cancer: a single-centre retrospective cohort study

Article References: Gou, X., Han, T., Yang, T., Yang, L., Kang, F., Wang, J., Yang, Y., Zhao, W., & Quan, Z. (2026). Comparison of diagnostic performance between MRI and ⁶⁸Ga-FAPI-04 PET/CT for stratified preoperative TNM staging of rectal cancer: a single-centre retrospective cohort study. BMC Medical Imaging. https://doi.org/10.1186/s12880-026-02697-2

Image Credits: AI Generated

DOI: 10.1186/s12880-026-02697-2

Keywords: rectal cancer, MRI, FAPI PET/CT, tumor staging, TNM staging, molecular imaging, TLU, BMC Medical Imaging, Comparison, diagnostic, performance, between