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Biodistribution and first clinical results of 18F-SiFAlin-TATE PET: a novel 18F-labeled somatostatin analog for imaging of neuroendocrine tumors

  • Harun IlhanEmail author
  • S. Lindner
  • A. Todica
  • C. C. Cyran
  • R. Tiling
  • C. J. Auernhammer
  • C. Spitzweg
  • S. Boeck
  • M. Unterrainer
  • F. J. Gildehaus
  • G. Böning
  • K. Jurkschat
  • C. Wängler
  • B. Wängler
  • R. Schirrmacher
  • P. Bartenstein
Original Article
  • 94 Downloads
Part of the following topical collections:
  1. Oncology – General

Abstract

Introduction

PET/CT using 68Ga-labeled somatostatin analogs (SSA) targeting somatostatin receptors (SSR) on the cell surface of well-differentiated neuroendocrine tumors (NET) represents the clinical reference standard for imaging. However, economic and logistic challenges of the 68Ge/68Ga generator-based approach have disadvantages over 18F-labeled compounds. Here, we present the first in-human data of 18F-SiFAlin-TATE, a novel 18F-labeled, SSR-targeting peptide. The aim was to compare the intra-individual biodistribution, tumor uptake, and image quality of 18F-SiFAlin-TATE to the clinical reference standard 68Ga-DOTA-TOC.

Methods

Thirteen patients with NET staged with both 68Ga-DOTA-TOC and 18F-SiFAlin-TATE PET/CT have been included in this retrospective analysis. We compared the biodistribution in normal organs and tumor uptake of NET lesions by SUVmean and SUVmax measurement for tracers. Additionally mean and max tumor-to-liver (TLR) and tumor-to-spleen ratios (TSR) have been calculated by division of SUVmean and SUVmax of tumor lesions by the SUVmean of the liver and spleen, respectively. Additionally, image quality was visually rated by 5 blinded readers and an intra-class correlation (ICC) analysis on inter-observer agreement has been performed.

Results

Compared with 68Ga-DOTA-TOC, the biodistribution of 18F-SiFAlin-TATE showed somewhat higher, however, statistically not significant higher uptake in the liver, spleen, and adrenal glands. Significantly higher uptake was observed in the kidneys. Tumor uptake was higher in most tumor lesions with significantly higher uptake in common metastatic sites of NET including the liver (SUVmax 18.8 ± 8.4 vs. 12.8 ± 5.6; p < 0.001), lymph nodes (SUVmax 23.8 ± 20.7 vs. 17.4 ± 16.1; p < 0.001) and bone (SUVmax 16.0 ± 10.1 vs. 10.3 ± 5.7; p < 0.01) for 18F-SiFAlin-TATE. The high tumor uptake resulted in favorable TLR and TSR, comparable with that of 68Ga-DOTA-TOC. The ICC analysis on the inter-observer agreement on image quality was substantial and almost perfect. Image quality was rated as excellent in most cases in both 68Ga-DOTA-TOC and 18F-SiFAlin-TATE PET.

Conclusion

The favorable characteristics of 18F-SiFAlin-TATE with a high image quality, the kit-like labeling procedure, and the promising clinical performance enable improved logistics and diagnostic possibilities for PET imaging of NET. Our first clinical results warrant further systematic studies investigating the clinical use of 18F-SiFAlin-TATE in NET patients.

Keywords

NET PET/CT imaging Somatostatin receptor imaging 68Ga-DOTA-TOC 18F-SiFAlin-TATE 18F labeling 

Notes

Compliance with ethical standards

Conflict of interest

HI is an advisory board member of Bayer, received research funding from Novartis and speaker honoraria from Bayer and Ipsen. CA received research contracts from Ipsen, Novartis, and ITM Solucin; lecture honoraria from Ipsen, Novartis, and Falk Foundation; and advisory board honoraria from Novartis. CS received research grants from Novartis; lecture honoraria from Ipsen and Novartis; and advisory board honoraria from Ipsen, Novartis, and Pfizer. All other authors declare no competing interests.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Harun Ilhan
    • 1
    • 2
    Email author
  • S. Lindner
    • 1
  • A. Todica
    • 1
    • 2
  • C. C. Cyran
    • 3
  • R. Tiling
    • 1
  • C. J. Auernhammer
    • 2
    • 4
  • C. Spitzweg
    • 2
    • 4
  • S. Boeck
    • 2
    • 5
  • M. Unterrainer
    • 1
  • F. J. Gildehaus
    • 1
  • G. Böning
    • 1
  • K. Jurkschat
    • 6
  • C. Wängler
    • 7
  • B. Wängler
    • 8
  • R. Schirrmacher
    • 9
  • P. Bartenstein
    • 1
    • 2
  1. 1.Department of Nuclear Medicine, University HospitalLMU MunichMunichGermany
  2. 2.ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM)University Hospital of MunichMunichGermany
  3. 3.Department of Radiology, University HospitalLMU MunichMunichGermany
  4. 4.Department of Internal Medicine 4, University HospitalLMU MunichMunichGermany
  5. 5.Department of Internal Medicine 3, University HospitalLMU MunichMunichGermany
  6. 6.Chair of Inorganic Chemistry II, Faculty of Chemistry and Chemical BiologyTechnical University of DortmundDortmundGermany
  7. 7.Biomedical Chemistry, Department of Clinical Radiology and Nuclear MedicineMedical Faculty Mannheim of Heidelberg UniversityMannheimGermany
  8. 8.Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear MedicineMedical Faculty Mannheim of Heidelberg UniversityMannheimGermany
  9. 9.Department of Oncology, Division of Oncological ImagingUniversity of AlbertaEdmontonCanada

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