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Comparison of 68Ga-DOTA-JR11 PET/CT with dosimetric 177Lu-satoreotide tetraxetan (177Lu-DOTA-JR11) SPECT/CT in patients with metastatic neuroendocrine tumors undergoing peptide receptor radionuclide therapy

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Abstract

Purpose

Paired imaging/therapy with radiolabeled somatostatin receptor (SSTR) antagonists is a novel approach in neuroendocrine tumors (NETs). The aim of this study was to compare tumor uptake of 68Ga-DOTA-JR11 and 177Lu-satoreotide tetraxetan (177Lu-DOTA-JR11) in patients with NETs.

Methods

As part of a prospective clinical trial, 20 patients with metastatic NETs underwent 68Ga-DOTA-JR11 PET/CT and serial imaging with 177Lu-satoreotide tetraxetan. PET/CT and SPECT/CT parameters for lesion uptake and absorbed dose of 177Lu-satoreotide tetraxetan in lesions were compared using linear regression analysis and Pearson correlation.

Results

A total of 95 lesions were analyzed on 68Ga-DOTA-JR11 PET/CT and 177Lu-satoreotide tetraxetan SPECT/CT. SUVs and tumor-to-normal-tissue ratios on PET/CT and SPECT/CT were significantly correlated (p < 0.01), but the degree of correlation was modest with Pearson correlation coefficients ranging from 0.3 to 0.7. Variation in intrapatient lesional correlation was observed. Nevertheless, in all patients, the lesion SUVpeak uptake ratio for 177Lu-satoreotide tetraxetan vs. 68Ga-DOTA-JR11 was high; even in those with low uptake on 68Ga-DOTA-JR11 PET/CT (SUVpeak ≤ 10), a ratio of 8.0 ± 5.2 was noted. Correlation of SUVpeak of 68Ga-DOTA-JR11 with projected 177Lu-satoreotide tetratexan-absorbed dose (n = 42) was modest (r = 0.5, p < 0.01), while excellent correlation of SUVpeak of 177Lu-satoreotide tetraxetan with projected 177Lu-satoreotide tetraxetan-absorbed dose was noted (r = 0.9, p < 0.0001).

Conclusion

Our study shows that 68Ga-DOTA-JR11 PET can be used for patient selection and PRRT and that low tumor uptake on PET should not preclude patients from treatment with 177Lu-satoreotide tetraxetan. The ability to use single time-point SPECT/CT for absorbed dose calculations could facilitate dosimetry regimens, save costs, and improve patient convenience.

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Acknowledgments

We gratefully acknowledge Rashid Ghani and members of the Nuclear Medicine Pharmacy; nuclear medicine nurses Ann Longing and Louise Harris for their help in patient management; clinical research coordinators Alicia Lashley, Hanh Pham, and Martha Ziolkowska, and Clinical Research Manager Bolorsukh Gansukh for their excellent support with patient flow and protocol management; the radiation safety officers and nuclear medicine technologists for their excellent technical assistance; and members of the Department of Medicine at MSK for patient referral. We also thank Leah Bassity for her assistance in editing this manuscript.

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Not applicable.

Funding

This study was supported in part by the Geoffrey Beene Cancer Research Center at MSK, and the MSK Radiochemistry and Molecular Imaging Probe Core was funded in part through NIH/NCI Cancer Center Support Grant P30 CA008748. We gratefully acknowledge funding from the Neuroendocrine Tumor Research Foundation (NETRF) (previously known as the Caring for Carcinoid Foundation). S.K. was supported in part by NIH/NCI Paul Calabresi Career Development Award for Clinical Oncology K12 CA184746 and by the Clinical and Translational Science Center at Weill Cornell Medical Center and MSK (grant number UL1TR00457). J.S.L. acknowledges support from NIH R35 CA232130. The precursor used in this study was provided by Ipsen.

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Authors and Affiliations

  1. Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Simone Krebs, Serge K. Lyashchenko, Jason S. Lewis, Lisa Bodei, Wolfgang A. Weber & Neeta Pandit-Taskar

  2. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Joseph A. O’Donoghue, Evan Biegel & Bradley J. Beattie

  3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Diane Reidy

  4. Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Serge K. Lyashchenko & Jason S. Lewis

  5. Department of Radiology, Weill Cornell Medical College, New York, NY, USA

    Serge K. Lyashchenko, Jason S. Lewis, Lisa Bodei, Wolfgang A. Weber & Neeta Pandit-Taskar

  6. Department of Nuclear Medicine, Technical University of Munich, Munich, Germany

    Wolfgang A. Weber

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  1. Simone Krebs
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Correspondence to Simone Krebs.

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Conflict of interest

J. A. O’Donoghue is a consultant for Janssen Pharmaceuticals, Inc. D. Reidy is on advisory boards for Novartis, Ipsen and AAA and has received research support from Novartis, Merck, and Ipsen. J. Lewis serves on advisory boards and has received compensation (or stock) from pHLIP, Inc., Clarity Pharmaceuticals, Varian Medical Systems, InVicro, Inc., Evergreen Theragnostics, Inc., Telix Pharmaceuticals Ltd., and Trace-Ability, Inc. He is a consultant for TPG Capital, L.P., and has received research support (financial and/or reagents) from Eli Lilly and Company, Sapience Therapeutics, Inc., Mabvax Therapeutics Holdings Inc., SibTech, Inc., Thermo Fisher Scientific, ImaginAb, Inc. U.S., Merck & Company, Inc., AbbVie Inc., Bristol-Myers Squibb Company, Genentech, Inc., Y-mAbs Therapeutics, Inc., and Regeneron Pharmaceuticals, Inc. L. Bodei is a consultant (unpaid) for AAA, Ipsen, Clovis, and Curium and receives research support from AAA. W. Weber is on advisory boards and receives compensation from Bayer, Blue Earth Diagnostics, Endocyte, Pentixapharm, and ITG. He has received research support from BMS, Imaginab, Ipsen, and Piramal. N. Pandit-Taskar is a consultant, receives honoraria or serves on the advisory board for Actinium Pharma, Progenics, Medimmune/Astrazeneca, and conducted research supported by Imaginab, Genentech, Janssen. S. Krebs, E. Biegel, B.J. Beattie, and S.K. Lyashchenko declare that they have no conflicts of interest.

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All procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Krebs, S., O’Donoghue, J.A., Biegel, E. et al. Comparison of 68Ga-DOTA-JR11 PET/CT with dosimetric 177Lu-satoreotide tetraxetan (177Lu-DOTA-JR11) SPECT/CT in patients with metastatic neuroendocrine tumors undergoing peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 47, 3047–3057 (2020). https://doi.org/10.1007/s00259-020-04832-9

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