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Preclinical evaluation and pilot clinical study of [68Ga]Ga-THP-APN09, a novel PD-L1 targeted nanobody radiotracer for rapid one-step radiolabeling and PET imaging

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Abstract

Purpose

Programmed cell death protein-1/ligand-1 (PD-1/L1) blockade has been a breakthrough in the treatment of patients with non-small cell lung cancer (NSCLC), but there is still a lack of effective methods to screen patients. Here we report a novel 68 Ga-labeled nanobody [68 Ga]Ga-THP-APN09 for PET imaging of PD-L1 status in mouse models and a first-in-human study in NSCLC patients.

Methods

[68 Ga]Ga-THP-APN09 was prepared by site-specific radiolabeling, with no further purification. Cell uptake assays were completed in the human lung adenocarcinoma cell line A549, NSCLC cell line H1975 and human PD-L1 gene-transfected A549 cells (A549PD−L1). The imaging to image PD-L1 status and biodistribution were investigated in tumor-bearing mice of these three tumor cell types. The first-in-human clinical translational trial was registered as NCT05156515. The safety, radiation dosimetry, biodistribution, and correlations of tracer uptake with immunohistochemical staining and major pathologic response (MPR) were evaluated in NSCLC patients who underwent adjuvant immunotherapy combined with chemotherapy.

Results

Radiosynthesis of [68 Ga]Ga-THP-APN09 was achieved at room temperature and a pH of 6.0–6.5 in 10 min with a high radiochemical yield (> 99%) and 13.9–27.8 GBq/μmol molar activity. The results of the cell uptake study reflected variable levels of surface PD-L1 expression observed by flow cytometry in the order A549PD−L1 > H1975 > A549. In small-animal PET/CT imaging, H1975 and A549PD−L1 tumors were clearly visualized in an 8.3:1 and 2.2:1 ratios over PD-L1-negative A549 tumors. Ex vivo biodistribution studies showed that tumor uptake was consistent with the PET results, with the highest A549PD−L1 being taken up the most (8.20 ± 0.87%ID/g), followed by H1975 (3.69 ± 0.50%ID/g) and A549 (0.90 ± 0.16%ID/g). Nine resectable NSCLC patients were enrolled in the clinical study. Uptake of [68 Ga]Ga-THP-APN09 was mainly observed in the kidneys and spleen, followed by low uptake in bone marrow. The radiation dose is within a reliable range. Tumor uptake was positively correlated with PD-L1 expression TPS (rs = 0.8763, P = 0.019). Tumor uptake of [68 Ga]Ga-THP-APN09 (SUVmax) in MPR patients was higher than that in non-MPR patients (median SUVmax 2.73 vs. 2.10, P = 0.036, determined with Mann–Whitney U-test).

Conclusion

[68 Ga]Ga-THP-APN09 has the potential to be transformed into a kit-based radiotracer for rapid, simple, one-step, room temperature radiolabeling. The tracer can detect PD-L1 expression levels in tumors, and it may make it possibility to predict the response of PD-1 immunotherapy combined with chemotherapy. Confirmation in a large number of cases is needed.

Trial registration

Clinical Trial (NCT05156515). Registered 12 December 2021.

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Data Availability

All data reported in this study can be found in the main manuscript or the supplementary materials. Correspondence and request for materials should be addressed to the corresponding authors.

References

  1. Gong J, Chehrazi-Raffle A, Reddi S, Salgia R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer. 2018;6:8. https://doi.org/10.1186/s40425-018-0316-z.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kim TK, Vandsemb EN, Herbst RS, Chen L. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nat Rev Drug Discovery. 2022;21:529–40. https://doi.org/10.1038/s41573-022-00493-5.

    Article  CAS  PubMed  Google Scholar 

  3. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018;379:2342–50. https://doi.org/10.1056/NEJMoa1809697.

    Article  CAS  PubMed  Google Scholar 

  4. Vansteenkiste J, Wauters E, Reymen B, Ackermann CJ, Peters S, De Ruysscher D. Current status of immune checkpoint inhibition in early-stage NSCLC. Ann Oncol. 2019;30:1244–53. https://doi.org/10.1093/annonc/mdz175.

    Article  CAS  PubMed  Google Scholar 

  5. Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2021;18:345–62. https://doi.org/10.1038/s41571-021-00473-5.

    Article  CAS  PubMed  Google Scholar 

  6. Lu S, Stein JE, Rimm DL, Wang DW, Bell JM, Johnson DB, et al. Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint Blockade: A Systematic Review and Meta-analysis. JAMA Oncol. 2019;5:1195–204. https://doi.org/10.1001/jamaoncol.2019.1549.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hofman P. The challenges of evaluating predictive biomarkers using small biopsy tissue samples and liquid biopsies from non-small cell lung cancer patients. J Thorac Dis. 2019;11:S57-s64. https://doi.org/10.21037/jtd.2018.11.85.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kluger HM, Zito CR, Turcu G, Baine MK, Zhang H, Adeniran A, et al. PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors. Clin Cancer Res. 2017;23:4270–9. https://doi.org/10.1158/1078-0432.Ccr-16-3146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Aguiar PN Jr, De Mello RA, Hall P, Tadokoro H, Lima LG. PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data. Immunotherapy. 2017;9:499–506. https://doi.org/10.2217/imt-2016-0150.

    Article  CAS  PubMed  Google Scholar 

  10. Shukuya T, Carbone DP. Predictive Markers for the Efficacy of Anti-PD-1/PD-L1 Antibodies in Lung Cancer. J Thorac Oncol. 2016;11:976–88. https://doi.org/10.1016/j.jtho.2016.02.015.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sacher AG, Gandhi L. Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non-Small-Cell Lung Cancer: A Review. JAMA Oncol. 2016;2:1217–22. https://doi.org/10.1001/jamaoncol.2016.0639.

    Article  PubMed  Google Scholar 

  12. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. The Lancet. 2017;389:255–65. https://doi.org/10.1016/s0140-6736(16)32517-x.

    Article  Google Scholar 

  13. Bensch F, van der Veen EL, Lub-de Hooge MN, Jorritsma-Smit A, Boellaard R, Kok IC, et al. (89)Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Nat Med. 2018;24:1852–8. https://doi.org/10.1038/s41591-018-0255-8.

    Article  CAS  PubMed  Google Scholar 

  14. Smit J, Borm FJ, Niemeijer AN, Huisman MC, Hoekstra OS, Boellaard R, et al. PD-L1 PET/CT Imaging with Radiolabeled Durvalumab in Patients with Advanced-Stage Non-Small Cell Lung Cancer. J Nucl Med. 2022;63:686–93. https://doi.org/10.2967/jnumed.121.262473.

    Article  CAS  PubMed  Google Scholar 

  15. Verhoeff SR, van de Donk PP, Aarntzen E, Oosting SF, Brouwers AH, Miedema IHC, et al. (89)Zr-DFO-Durvalumab PET/CT Before Durvalumab Treatment in Patients with Recurrent or Metastatic Head and Neck Cancer. J Nucl Med. 2022;63:1523–30. https://doi.org/10.2967/jnumed.121.263470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Niemeijer AN, Leung D, Huisman MC, Bahce I, Hoekstra OS, van Dongen G, et al. Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer. Nat Commun. 2018;9:4664. https://doi.org/10.1038/s41467-018-07131-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Huisman MC, Niemeijer AN, Windhorst AD, Schuit RC, Leung D, Hayes W, et al. Quantification of PD-L1 Expression with (18)F-BMS-986192 PET/CT in Patients with Advanced-Stage Non-Small Cell Lung Cancer. J Nucl Med. 2020;61:1455–60. https://doi.org/10.2967/jnumed.119.240895.

    Article  PubMed  Google Scholar 

  18. Nienhuis PH, Antunes IF, Glaudemans A, Jalving M, Leung D, Noordzij W, et al. (18)F-BMS986192 PET Imaging of PD-L1 in Metastatic Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors: A Pilot Study. J Nucl Med. 2022;63:899–905. https://doi.org/10.2967/jnumed.121.262368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhou X, Jiang J, Yang X, Liu T, Ding J, Nimmagadda S, et al. First-in-Humans Evaluation of a PD-L1-Binding Peptide PET Radiotracer in Non-Small Cell Lung Cancer Patients. J Nucl Med. 2022;63:536–42. https://doi.org/10.2967/jnumed.121.262045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhou M, Wang X, Chen B, Xiang S, Rao W, Zhang Z, et al. Preclinical and first-in-human evaluation of (18)F-labeled D-peptide antagonist for PD-L1 status imaging with PET. Eur J Nucl Med Mol Imaging. 2022;49:4312–24. https://doi.org/10.1007/s00259-022-05876-9.

    Article  CAS  PubMed  Google Scholar 

  21. Verhaar ER, Woodham AW, Ploegh HL. Nanobodies in cancer. Semin Immunol. 2021;52:101425. https://doi.org/10.1016/j.smim.2020.101425.

    Article  CAS  PubMed  Google Scholar 

  22. Wei W, Younis MH, Lan X, Liu J, Cai W. Single-Domain Antibody Theranostics on the Horizon. J Nucl Med. 2022;63:1475–9. https://doi.org/10.2967/jnumed.122.263907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yang EY, Shah K. Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics. Front Oncol. 2020;10:1182. https://doi.org/10.3389/fonc.2020.01182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lv G, Sun X, Qiu L, Sun Y, Li K, Liu Q, et al. PET Imaging of Tumor PD-L1 Expression with a Highly Specific Nonblocking Single-Domain Antibody. J Nucl Med. 2020;61:117–22. https://doi.org/10.2967/jnumed.119.226712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Qin X, Guo X, Liu T, Li L, Zhou N, Ma X, et al. High in-vivo stability in preclinical and first-in-human experiments with [(18)F]AlF-RESCA-MIRC213: a (18)F-labeled nanobody as PET radiotracer for diagnosis of HER2-positive cancers. Eur J Nucl Med Mol Imaging. 2023;50:302–13. https://doi.org/10.1007/s00259-022-05967-7.

    Article  CAS  PubMed  Google Scholar 

  26. Hu B, Liu T, Li L, Shi L, Yao M, Li C, et al. IgG-Binding Nanobody Capable of Prolonging Nanobody-Based Radiotracer Plasma Half-Life and Enhancing the Efficacy of Tumor-Targeted Radionuclide Therapy. Bioconjug Chem. 2022;33:1328–39. https://doi.org/10.1021/acs.bioconjchem.2c00209.

    Article  CAS  PubMed  Google Scholar 

  27. Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54. https://doi.org/10.1007/s00259-014-2961-x.

    Article  CAS  PubMed  Google Scholar 

  28. Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018;378:2288–301. https://doi.org/10.1056/NEJMoa1716948.

    Article  CAS  PubMed  Google Scholar 

  29. Ilie M, Long-Mira E, Bence C, Butori C, Lassalle S, Bouhlel L, et al. Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies. Ann Oncol. 2016;27:147–53. https://doi.org/10.1093/annonc/mdv489.

    Article  CAS  PubMed  Google Scholar 

  30. Mayer AT, Natarajan A, Gordon SR, Maute RL, McCracken MN, Ring AM, et al. Practical Immuno-PET Radiotracer Design Considerations for Human Immune Checkpoint Imaging. J Nucl Med. 2017;58:538–46. https://doi.org/10.2967/jnumed.116.177659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Young JD, Abbate V, Imberti C, Meszaros LK, Ma MT, Terry SYA, et al. (68)Ga-THP-PSMA: A PET Imaging Agent for Prostate Cancer Offering Rapid, Room-Temperature, 1-Step Kit-Based Radiolabeling. J Nucl Med. 2017;58:1270–7. https://doi.org/10.2967/jnumed.117.191882.

    Article  CAS  PubMed  Google Scholar 

  32. Derlin T, Schmuck S, Juhl C, Zorgiebel J, Schneefeld SM, Walte ACA, et al. PSA-stratified detection rates for [(68)Ga]THP-PSMA, a novel probe for rapid kit-based (68)Ga-labeling and PET imaging, in patients with biochemical recurrence after primary therapy for prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:913–22. https://doi.org/10.1007/s00259-017-3924-9.

    Article  CAS  PubMed  Google Scholar 

  33. Donnelly DJ, Smith RA, Morin P, Lipovsek D, Gokemeijer J, Cohen D, et al. Synthesis and Biologic Evaluation of a Novel (18)F-Labeled Adnectin as a PET Radioligand for Imaging PD-L1 Expression. J Nucl Med. 2018;59:529–35. https://doi.org/10.2967/jnumed.117.199596.

    Article  CAS  PubMed  Google Scholar 

  34. Crauwels M, Massa S, Martin C, Betti C, Ballet S, Devoogdt N, et al. Site-Specific Radioactive Labeling of Nanobodies. Methods Mol Biol (Clifton, NJ). 2018;1827:505–40. https://doi.org/10.1007/978-1-4939-8648-4_26.

    Article  CAS  Google Scholar 

  35. Satpati D, Shinto A, Kamaleshwaran KK, Sane S, Banerjee S. Convenient Preparation of [(68)Ga]DKFZ-PSMA-11 Using a Robust Single-Vial Kit and Demonstration of Its Clinical Efficacy. Mol Imaging Biol. 2016;18:420–7. https://doi.org/10.1007/s11307-016-0943-z.

    Article  CAS  PubMed  Google Scholar 

  36. Altunay B, Goedicke A, Winz OH, Hertel F, von Mallek D, Meszaros LK, et al. (99m)Tc-labeled single-domain antibody for SPECT/CT assessment of HER2 expression in diverse cancer types. Eur J Nucl Med Mol Imaging. 2023;50:1005–13. https://doi.org/10.1007/s00259-022-06066-3.

    Article  CAS  PubMed  Google Scholar 

  37. Altunay B, Morgenroth A, Beheshti M, Vogg A, Wong NCL, Ting HH, et al. HER2-directed antibodies, affibodies and nanobodies as drug-delivery vehicles in breast cancer with a specific focus on radioimmunotherapy and radioimmunoimaging. Eur J Nucl Med Mol Imaging. 2021;48:1371–89. https://doi.org/10.1007/s00259-020-05094-1.

    Article  CAS  PubMed  Google Scholar 

  38. Behr TM, Goldenberg DM, Becker W. Reducing the renal uptake of radiolabeled antibody fragments and peptides for diagnosis and therapy: present status, future prospects and limitations. Eur J Nucl Med. 1998;25:201–12. https://doi.org/10.1007/s002590050216.

    Article  CAS  PubMed  Google Scholar 

  39. Chen X, Gao A, Zhang F, Yang Z, Wang S, Fang Y, et al. ILT4 inhibition prevents TAM- and dysfunctional T cell-mediated immunosuppression and enhances the efficacy of anti-PD-L1 therapy in NSCLC with EGFR activation. Theranostics. 2021;11:3392–416. https://doi.org/10.7150/thno.52435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, et al. PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211:781–90. https://doi.org/10.1084/jem.20131916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tracy SI, Venkatesh H, Hekim C, Heltemes-Harris LM, Knutson TP, Bachanova V, et al. Combining nilotinib and PD-L1 blockade reverses CD4+ T-cell dysfunction and prevents relapse in acute B-cell leukemia. Blood. 2022;140:335–48. https://doi.org/10.1182/blood.2021015341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fricke J, Mambetsariev I, Pharaon R, Subbiah S, Rajurkar S, Salgia R. Hyperprogression on immunotherapy with complete response to chemotherapy in a NSCLC patient with high PD-L1 and STK11: A case report. Medicine (Baltimore). 2020;99:e22323. https://doi.org/10.1097/md.0000000000022323.

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Acknowledgements

The authors would like to thank Dr. Huifang Tian, Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education), Central Laboratory, Peking University Cancer Hospital & Institute (Beijing, China) for her technical assistance in MALDI analysis.

Funding

This research was supported by grants from the National Natural Science Foundation of China, grant number (No. 81871416, 82172006); the Capital’s Funds for Health Improvement and Research (No. 2022-2Z-2154 and 2022-2Z-2155); the Beijing Millions of Talent Projects A level funding, grant number (No. 2019A38); the Beijing Hospitals Authority Deng feng Project (DFL20191102); the Beijing Municipal Administration of Hospitals Yang fan Project (ZYLX201816); the Pilot Project (4th Round) to Reform Public Development of Beijing Municipal Medical Research Institute (2021–1).

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  1. Xiaopan Ma, Xin Zhou and Biao Hu are authors contributed equally to this work.

Authors and Affiliations

  1. Medical College, Guizhou University, Guiyang, 550025, China

    Xiaopan Ma

  2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, No.52 Fucheng Rd., Beijing, 100142, China

    Xiaopan Ma, Xin Zhou, Liqiang Li, Xue Qin, DaPeng Li, Yuan Yao, Xingguo Hou, Song Liu, Yan Chen, Zilei Wang, Wenyuan Zhou, Nan Li, Hua Zhu & Zhi Yang

  3. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, No.38 Xueyuan Rd., Beijing, 100191, China

    Biao Hu, Xiaoda Li, Meinan Yao & Bing Jia

  4. Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

    Biao Hu

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Contributions

NL, HZ, BJ and ZY conceived and designed this research. XM was responsible for all experiments, data collection and analysis, and wrote the manuscript. XZ was responsible for the recruitment of patients and image analysis. BH was responsible for screening and identification of the nanobody. XL, MY, LL, and XQ were involved in the preparation of radiopharmaceuticals. DL, YY, XH, SL, YC, and ZW took part in some animal experiments. WZ was involved in immunohistochemical experiments on animal tumors.

Corresponding authors

Correspondence to Nan Li, Hua Zhu, Bing Jia or Zhi Yang.

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All clinical studies were approved by the Medical Ethics Committee of Beijing Cancer Hospital (2021KT111), and registered in the Clinical Trial (NCT05156515). All animal studies were performed according to the guidelines of the Animal Care and Use Committee of Perking University Cancer Hospital.

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Written informed consent was obtained from all participants included in the study.

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Ma, X., Zhou, X., Hu, B. et al. Preclinical evaluation and pilot clinical study of [68Ga]Ga-THP-APN09, a novel PD-L1 targeted nanobody radiotracer for rapid one-step radiolabeling and PET imaging. Eur J Nucl Med Mol Imaging 50, 3838–3850 (2023). https://doi.org/10.1007/s00259-023-06373-3

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