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Tumor-to-blood ratio for assessment of fibroblast activation protein receptor density in pancreatic cancer using [68Ga]Ga-FAPI-04

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

[68Ga]Ga-FAPI PET/CT has been widely used in clinical diagnosis and radiopharmaceutical therapy. In this study, tumor-to-blood ratio (TBR) was evaluated as a powerful tool for semiquantitative assessment of [68Ga]Ga-FAPI-04 tumor uptake and as an effective index for tumors with high FAP expression in theranostics.

Methods

Nine patients with pancreatic cancer underwent a 60-min dynamic PET/CT scan by total-body PET/CT (with a long AFOV of 194 cm) after injection of [68Ga]Ga-FAPI-04. After dynamic PET/CT scan, three patients received chemotherapy and underwent the second dynamic scan to evaluate treatment response. Time-activity curves (TACs) were obtained by drawing regions of interest for primary pancreatic lesions and metastatic lesions. The lesion TACs were fitted using four compartment models by the software PMOD PKIN kinetic modeling. The preferred pharmacokinetic model for [68Ga]Ga-FAPI-04 was evaluated based on the Akaike information criterion. The correlations between simplified methods for quantification of [68Ga]Ga-FAPI-04 (SUVs; tumor-to-blood ratios [TBRs]) and the total distribution volume (Vt) estimates obtained from pharmacokinetic analysis were calculated.

Results

In total, 9 primary lesions and 25 metastatic lesions were evaluated. The reversible two-tissue compartment model (2TCM) was the most appropriate model among the four compartment models. The total distribution volume Vt values derived from 2TCM varied significantly in pathological lesions and background regions. A strong positive correlation was observed between TBRmean and Vt from the 2TCM model in pathological lesions (R2=0.92, P<0.001). The relative difference range for TBRmean was 2.1% compared to the reduction rate of Vt in the patients who were treated with chemotherapy.

Conclusions

A strong positive correlation was observed between TBRmean and Vt for [68Ga]Ga-FAPI-04. TBRmean reflects FAP receptor density better than SUVmean and SUVmax, and would be the preferred measurement tool for semiquantitative assessment of [68Ga]Ga-FAPI-04 tumor uptake and as a means for evaluating treatment response.

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Data availability

The data could be obtained from the corresponding author upon request.

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Funding

The study was supported by National Key R&D Program of China (No. 2021YFA0910004); National Natural Science Foundation of China (No. 82171972); Clinical Research Project of Health Industry of Shanghai Municipal Health Commission (20214Y0438); and Nurture projects for the Youth Medical Talents-Medical Imaging Practitioners Program (SHWRS(2021)_099).

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Correspondence to Gang Huang, Yun Zhou or Jianjun Liu.

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The study involving human participants was in line with the principles of the ethics committee in Renji hospital and the declaration of Helsinki in 1964. Animal-based research was not included in this study.

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The informed consent was waived.

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The authors declare no competing interests.

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This article is part of the Topical Collection on Oncology - Digestive tract

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ESM 1

The maximum intensity projection of dynamic reconstructed images with 92 frames. The animation lasts 92 seconds, and each second represents one frame. (DOCX 5382 kb)

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Chen, R., Yang, X., Yu, X. et al. Tumor-to-blood ratio for assessment of fibroblast activation protein receptor density in pancreatic cancer using [68Ga]Ga-FAPI-04. Eur J Nucl Med Mol Imaging 50, 929–936 (2023). https://doi.org/10.1007/s00259-022-06010-5

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