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Dose escalation of an Evans blue–modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors

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

Abstract

Purpose

To evaluate the safety and efficacy of 177Lu-DOTA-EB-TATE, a radiolabeled somatostatin analog modified by Evans blue, at escalating doses, was used to increase tumor retention in patients with progressive metastatic neuroendocrine tumors (NETs).

Methods

Thirty-three patients with metastatic NETs were prospectively enrolled into four groups: group A (n = 6, 43 ± 12 years) administered approximately 3.7 GBq (100 mCi) 177Lu-DOTATATE as controls; group B (n = 7, 55 ± 7 years) administered approximately 1.11 GBq (30 mCi) 177Lu-DOTA-EB-TATE; group C (n = 6, 55 ± 10 years) administered approximately 1.85 GBq (50 mCi) 177Lu-DOTA-EB-TATE; group D (n = 14, 50 ± 10 years) administered approximately 3.7 GBq (100 mCi) 177Lu-DOTA-EB-TATE. Treatment-related adverse events were graded according to the CTCAE v.5.0. 68Ga-DOTATATE PET/CT were performed at baseline and 2–3 months after treatment for response evaluation.

Results

Administration was well tolerated. No CTC 3/4 hematotoxicity, nephrotoxicity, or hepatotoxicity was observed during or after treatment in groups A–C. In group D, CTC-3 hematotoxicity was recorded in 2 patients with multicourse chemotherapy previously. After one-cycle treatment, the SUVmax decreased in group C (Δ% = − 17.4 ± 29.3%) and group D (Δ% = − 15.1 ± 39.1%), but greatly increased in group B (Δ% = 30.0 ± 68.0%) and mildly increased in group A (Δ% = 5.4 ± 45.9%). Referring to EORTC criteria, 16.7% (1/6), 0% (0/7), 50% (3/6), and 50% (7/14) were evaluated as partial response in groups A, B, C, and D, respectively. When selecting lesions with comparable baseline SUVmax ranging from 15 to 40, SUVmax showed no significant decrease in group B (Δ% = − 7.3 ± 24.5%) (P = 0.214), significant decrease in group C (Δ% = − 34.9 ± 12.4%) (P = 0.001), and in group D (Δ% = − 17.9 ± 19.7%) (P = 0.012) as compared with group A with increased SUVmax (Δ% = 8.4 ± 48.8%). SUVmax significantly decreased in the EBTATE groups (groups B–D combined) (Δ% = − 19.0 ± 21.5%) as compared with the TATE group (P = 0.045).

Conclusion

177Lu-DOTA-EB-TATE is well tolerated and is more effective than 177Lu-DOTATATE. Both 1.85 GBq (50 mCi) and 3.7 GBq (100 mCi) doses appear to be more effective than 1.11 GBq (30 mCi) dose. Further investigation with more cycles of 177Lu-DOTA-EB-TATE treatment and longer follow-up is warranted.

Trial registration

Treatment Using 177Lu-DOTA-EB-TATE in Patients with Advanced Neuroendocrine Tumors (NCT03478358). URL: https://register.clinicaltrials.gov/prs/app/action/ViewOrUnrelease?uid=U0001JRW&ts=13&sid=S0007RNX&cx=y3yqv4

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Funding

This study was supported by the Key Project on Inter-Governmental International Scientific and Technological Innovation Cooperation in National Key Projects of Research and Development Plan (2016YFE0115400), the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), and was also partly supported by the Chinese Academy of Medical Science Major Collaborative Innovation Project (2016-I2M-1-011), Capital Health Development Scientific Research Project (2018-1-4011), National Nature Science Foundation (81871392, 81741142, 3316 81701742), and Beijing Municipal Natural Science Foundation (7161012).

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Authors and Affiliations

  1. Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Qingxing Liu, Jie Zang, Huimin Sui, Hao Wang & Zhaohui Zhu

  2. Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, 100730, China

    Qingxing Liu, Jie Zang, Huimin Sui, Hao Wang & Zhaohui Zhu

  3. Oncology Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Yuejuan Cheng

  4. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 35A Convent Dr., GD937, Bethesda, MD, 20892, USA

    Orit Jacobson & Xiaoyuan Chen

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  1. Qingxing Liu
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Correspondence to Zhaohui Zhu or Xiaoyuan Chen.

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All procedures involving human participants in studies were in accordance with the ethical standards of the Institute Review Board of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Liu, Q., Cheng, Y., Zang, J. et al. Dose escalation of an Evans blue–modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors. Eur J Nucl Med Mol Imaging 47, 947–957 (2020). https://doi.org/10.1007/s00259-019-04530-1

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