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The inferior performance of [68Ga]Ga-FAPI-04 PET/CT as a diagnostic and theranostic biomarker in [177Lu]Lu-DOTATATE refractory well-differentiated neuroendocrine tumors

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

Abstract

Purpose

We aimed to investigate the potential of [68Ga]Ga-FAPI-04 PET/CT as an alternative diagnostic and theranostic tool in well-differentiated NETs refractory to [177Lu]Lu-DOTATATE therapy.

Methods

Patients who received at least two cycles of [177Lu]Lu-DOTATATE therapy for metastatic NETs and progressed under treatment were included. All patients had performed [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI-04 PET/CT within 3 weeks. The number of PET-positive lesions related to NETs and tumor sites was documented. Mann-Whitney U and chi-square tests were used to compare SUVmax levels of tracers and the number of detected metastases.

Results

Twelve patients (7 male, 5 female) who met the eligibility criteria were included in the study. Ten patients had grade 1–2 NET of various origins, and two had paraganglioma and pheochromocytoma. One hundred ninety-eight of 230 lesions (86%) were SSTR positive with a median SUVmax of 16.6 (2.2–76.5), and 88 of 230 lesions (38.2%) were [68Ga]Ga-FAPI-04 positive with a median SUVmax of 5.1 (2.3–21). Median SUVmax level and detected number of tumors were significantly higher in [68Ga]Ga-DOTATATE PET/CT (p=<0.001). [68Ga]Ga-FAPI-04 PET/CT was completely (n:2) or almost completely (n:3) negative in 5 (42%) patients. Two (17%) patients had flip-flop SSTR/FAPI uptake in tumors. In four patients (33%), tumor uptake or the number of PET-positive lesions was inferior in [68Ga]Ga-FAPI-04 PET/CT. In only one patient (8%), tumor uptakes were higher in [68Ga]Ga-FAPI-04 PET/CT. Low-dose [177Lu]Lu-FAPI-46 dosimetry was performed on the FAPI-dominant patient; absorbed radiation doses per GBq were 1.26 Gy, 0.36 Gy, 0.32 Gy, and 0.2 Gy for kidneys, liver, spleen, and total body, respectively. The mean absorbed dose per GBq was 0.33 Gy for liver mass and 0.41 Gy for metastatic lymph nodes.

Conclusion

Our preliminary results demonstrated that [68Ga]Ga-FAPI-04 PET/CT mainly failed in well-differentiated NETs refractory to [177Lu]Lu-DOTATATE therapy and had a limited role as an alternative diagnostic or theranostic agent. Further investigations with a larger patient population are required to determine the impact of [68Ga]Ga-FAPI-04 PET/CT on NETs.

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Authors and Affiliations

  1. Istanbul Faculty of Medicine, Department of Nuclear Medicine, Istanbul University, 34093 Fatih, Istanbul, Turkey

    Duygu Has Simsek, Dilara Denizmen, Yasemin Sanli, Fikret Buyukkaya, Bilal Kovan, Emine Goknur Isik, Zeynep Gozde Ozkan & Serkan Kuyumcu

  2. Gazi Yasargil Training and Research Hospital, Department of Nuclear Medicine, Saglik Bilimleri University, 21070 Kayapinar, Diyarbakir, Turkey

    Yunus Guzel & Halil Komek

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  1. Duygu Has Simsek
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This prospective study was approved by our institutional review board, and written informed consent was obtained from all patients.

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Has Simsek, D., Guzel, Y., Denizmen, D. et al. The inferior performance of [68Ga]Ga-FAPI-04 PET/CT as a diagnostic and theranostic biomarker in [177Lu]Lu-DOTATATE refractory well-differentiated neuroendocrine tumors. Eur J Nucl Med Mol Imaging 51, 828–840 (2024). https://doi.org/10.1007/s00259-023-06497-6

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