# Correlations between Ki67 expression and uptake of 68Ga-FAPI-04 versus 18F-FDG in different types of tumors: a lesion-based study

## TL;DR

This study compares how well two imaging agents, 68Ga-FAPI-04 and 18F-FDG, correlate with Ki67 expression in tumors, finding that 18F-FDG is more closely linked to tumor cell proliferation.

## Contribution

The study reveals that 18F-FDG PET/CT parameters correlate with Ki67, while 68Ga-FAPI-04 does not, suggesting different biological mechanisms.

## Key findings

- 18F-FDG SUVmax and TBR are moderately correlated with Ki67 expression (rho = 0.471 and 0.405, respectively).
- 68Ga-FAPI-04 uptake parameters show no significant correlation with Ki67 (rho = 0.121 and 0.119).
- 18F-FDG uptake is more consistent across tumor types compared to 68Ga-FAPI-04, which shows significant heterogeneity.

## Abstract

This study aimed to evaluate the correlation between Ki67 expression and uptake values of 68Ga-FAPI-04 and 18F-FDG PET/CT in different types of tumor lesions.

Patients who underwent concurrent 68Ga-FAPI-04 and 18F-FDG PET/CT and were candidates for biopsy of any lesion positive on either imaging agent were enrolled in this retrospective study. Receiver operating characteristic (ROC) curve analysis was conducted on Ki67 prediction of 18F-FDG and 68Ga-FAPI-04 positive lesions. The maximum standard uptake values (SUVmax) and tumor-to-background ratio (TBR) of the lesions were collected. The mean SUVmax and mean TBR of lesions from different tumor groups were compared using the Kruskal-Wallis test. Spearman rho test was used to analyze the correlation between the same parameters of two types of PET. The protein expression of Ki67 was examined by immunohistochemical staining. The correlation between the parameters of two imaging agents and Ki67 expression in tissue samples was analyzed by Spearman’s rho test.

A total of 66 patients were included (31 men, 35 women; mean age 56.11 ± 12.64 years), with 69 malignant tumor samples analyzed. All tumors exhibited Ki67 expression, with varying intensity and positivity rates ranging from 1% to 95%. ROC curve analysis showed that Ki67 expression had a good ability to predict visual positive of 18F-FDG (AUC = 0.819, p < 0.0001), but it did not have statistical significance in predicting positive of 68Ga-FAPI-04 (AUC = 0.698, p = 0.069). The optimal critical value for Ki67 was 15%. Overall, 18F-FDG SUVmax and TBR were moderately positively correlated with Ki67 (rho = 0.471, p < 0.0001 and rho = 0.405, P < 0.001, respectively), while the 68Ga-FAPI-04 parameters showed no significant correlation with Ki67 (rho = 0.121, p = 0.321 and rho = 0.119, P = 0.329, respectively). In subgroup analysis, the correlation between 18F-FDG (SUVmax and TBR) and Ki67 remained moderate in lesions with Ki67 > 15% (rho = 0.346, p = 0.008 and rho = 0.327, p = 0.013, respectively). 18F-FDG (SUVmax and TBR) and Ki67 also showed a particularly correlation in tumor groups of hematology and head and neck tumors. In any tumor group or Ki67 subgroup, there was no significant association between 68Ga-FAPI-04 (SUVmax and TBR) and Ki67. Regarding the correlation between two imaging agents, the tracer correlation in Ki67≤15% lesions is stronger than that in Ki67 > 15% lesions. Unlike 18F-FDG, which showed no difference between tumor groups (SUVmax: p = 0.260, TBR: p = 0.072), significant heterogeneity in 68Ga-FAPI-04 uptake was observed between different tumor groups (SUVmax: p = 0.002, TBR: p = 0.004).

Mechanistic differences likely exist between 68Ga-FAPI-04 and Ki67. In contrast, 18F-FDG may serve as a direct indicator for assessing tumor proliferative capacity. Limitations of this study could be addressed in future research with larger sample sizes and subgroup analyses to yield more valuable insights.

ChiCTR, ChiCTR2100044131. Registered 10 October 2022, https://www.chictr.org.cn, ChiCTR2100044131.