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OtherClinical Investigations (Human)

Prospective phase II trial of prognostication by 68Ga-NOTA-AE105 uPAR PET in patients with neuroendocrine neoplasms: Implications for uPAR targeted therapy

Esben Andreas Carlsen, Mathias Loft, Annika Loft, Anne Kiil Berthelsen, Seppo Wang Langer, Ulrich Knigge and Andreas Kjaer
Journal of Nuclear Medicine January 2022, jnumed.121.263177; DOI: https://doi.org/10.2967/jnumed.121.263177
Esben Andreas Carlsen
1 Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark; ENETS Neuroendocrine Tumor Center of Excel;
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Mathias Loft
1 Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark; ENETS Neuroendocrine Tumor Center of Excel;
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Annika Loft
1 Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark; ENETS Neuroendocrine Tumor Center of Excel;
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Anne Kiil Berthelsen
1 Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark; ENETS Neuroendocrine Tumor Center of Excel;
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Seppo Wang Langer
2 Dept. of Oncology & Dept. Clinical Medicine, Copenhagen University Hospital - Rigshospitalet & University of Copenhagen, Denmark; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Denmark;
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Ulrich Knigge
3 Depts. of Clinical Endocrinology and Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet, Denmark; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Denmark, Denmark
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Andreas Kjaer
1 Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark; ENETS Neuroendocrine Tumor Center of Excel;
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Abstract

The clinical course for patients with neuroendocrine neoplasms (NENs) ranges from indolent to highly aggressive. Non-invasive tools to improve prognostication and guide decisions on treatment are warranted. Expression of urokinase plasminogen activator receptor (uPAR) is present in many cancer types and associated with a poor outcome. Therefore, using an in-house developed uPAR PET tracer (68Ga-NOTA-AE105) we aimed to assess uPAR expression in NENs. We hypothesized that uPAR expression was detectable in a significant proportion of patients and associated with a poorer outcome. In addition, as uPAR-targeted radionuclide therapy has previously proven effective in preclinical models, the study would also indicate the potential for uPAR-targeted radionuclide therapy in NEN patients. METHODS: In a prospective clinical phase II trial, we included 120 patients with NENs of all grades of whom 96 subsequently had uPAR PET/CT performed with evaluable lesions. PET/CT was acquired 20 minutes after injection of approximately 200 MBq 68Ga-NOTA-AE105. uPAR target-to-liver ratio (uPAR TLR) was used to define lesions as uPAR positive when lesion SUVmax /liver SUVmean ≥ 2. Patients were followed for at least 1 year to assess progression-free survival (PFS) and overall survival (OS). RESULTS: The majority of patients had small intestinal NEN (n = 61) and metastatic disease (n = 86). uPAR positive lesions were seen in 68% (n = 65) of all patients and in 75% (n = 18) of patients with high grade disease (NEN G3). During follow-up (median 28 months), 59 patients (62%) experienced progressive disease and 28 patients (30%) died. High uPAR expression, defined as uPAR TLR above median, had a hazard ratio (95% confidence interval) of 1.87 (1.11-3.17) and 2.64 (1.19-5.88) for PFS and OS, respectively (p<0.05 for both). CONCLUSION: Using 68Ga-NOTA-AE105 PET for imaging uPAR in patients with NEN, uPAR positive lesions were seen in the majority of patients and most notably in patients with both low and high grade NEN. Furthermore, uPAR expression was associated with a worse prognosis. We suggest that uPAR PET is relevant for risk stratification and uPAR may be a promising target for therapy in patients with NEN.

  • Molecular Imaging
  • Neuroendocrine
  • PET/CT
  • Molecular imaging
  • Neuroendocrine neoplasms
  • PET
  • Prognosis
  • Urokinase plasminogen activator receptor (uPAR)
  • Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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Journal of Nuclear Medicine: 63 (7)
Journal of Nuclear Medicine
Vol. 63, Issue 7
July 1, 2022
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Prospective phase II trial of prognostication by 68Ga-NOTA-AE105 uPAR PET in patients with neuroendocrine neoplasms: Implications for uPAR targeted therapy
Esben Andreas Carlsen, Mathias Loft, Annika Loft, Anne Kiil Berthelsen, Seppo Wang Langer, Ulrich Knigge, Andreas Kjaer
Journal of Nuclear Medicine Jan 2022, jnumed.121.263177; DOI: 10.2967/jnumed.121.263177

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Prospective phase II trial of prognostication by 68Ga-NOTA-AE105 uPAR PET in patients with neuroendocrine neoplasms: Implications for uPAR targeted therapy
Esben Andreas Carlsen, Mathias Loft, Annika Loft, Anne Kiil Berthelsen, Seppo Wang Langer, Ulrich Knigge, Andreas Kjaer
Journal of Nuclear Medicine Jan 2022, jnumed.121.263177; DOI: 10.2967/jnumed.121.263177
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Keywords

  • molecular imaging
  • Neuroendocrine
  • PET/CT
  • neuroendocrine neoplasms
  • PET
  • prognosis
  • Urokinase plasminogen activator receptor (uPAR)
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