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Theranostics 2024; 14(3):1212-1223. doi:10.7150/thno.92481 This issue Cite

Research Paper

A novel approach to guide GD2-targeted therapy in pediatric tumors by PET and [⁶⁴Cu]Cu-NOTA-ch14.18/CHO

Nils Florian Trautwein^1,2, Johannes Schwenck^1,2,3, Christian Seitz^3,4, Ferdinand Seith⁵, Eduardo Calderón¹, Sebastian von Beschwitz¹, Stephan Singer⁶, Gerald Reischl^2,3, Rupert Handgretinger⁴, Jürgen Schäfer⁵, Peter Lang⁴, Bernd J. Pichler^2,3,7, Johannes H. Schulte⁴, Christian la Fougère^1,3,7✉, Helmut Dittmann¹

1. Department of Nuclear Medicine and Clinical Molecular Imaging, University of Tübingen.
2. Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen.
3. Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen.
4. Department of Pediatric Hematology and Oncology, University of Tübingen.
5. Department of Diagnostic and Interventional Radiology, University of Tübingen.
6. Department of Pathology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
7. German Cancer Consortium (DKTK), Partner Site Tübingen, Germany.

✉ Corresponding author: Christian la Fougère, Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University, Otfried-Müller-Straße 14, 72076 Tübingen, Germany. christian.lafougereuni-tuebingen.de.

Abstract

Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease. Therefore, a non-invasive approach for the assessment and visualization of GD2 expression in-vivo is of upmost interest and might enable a more appropriate treatment stratification.

Methods: Recently, [⁶⁴Cu]Cu-NOTA-ch14.18/CHO (⁶⁴Cu-GD2), a radiolabeled GD2-antibody for imaging with Positron-Emission-Tomography (PET) was developed. We here report our first clinical patients' series (n = 11) in different pediatric tumors assessed with ⁶⁴Cu-GD2 PET/MRI. GD2-expression in tumors and tissue uptake in organs was evaluated by semiquantitative measurements of standardized uptake values (SUV) with PET/MRI on day 1 p.i. (n = 11) as well as on day 2 p.i. (n = 6).

Results: In 8 of 9 patients with suspicious tumor lesions on PET/MRI at least one metastasis showed an increased ⁶⁴Cu-GD2 uptake and a high tracer uptake (SUV_max > 10) was measured in 4 of those 8 patients. Of note, sufficient image quality with high tumor to background contrast was readily achieved on day 1. In case of ⁶⁴Cu-GD2-positive lesions, an excellent tumor to background ratio (at least 6:1) was observed in bones, muscles or lungs, while lower tumor to background contrast was seen in the spleen, liver and kidneys. Furthermore, we demonstrated extensive tumor heterogeneity between patients as well as among different metastatic sites in individual patients. Dosimetry assessment revealed a whole-body dose of only 0.03 mGy/MBq (range 0.02-0.04).

Conclusion: ⁶⁴Cu-GD2 PET/MRI enables the non-invasive assessment of individual heterogeneity of GD2 expression, which challenges our current clinical practice of patient selection, stratification and immunotherapy application scheme for treatment with anti-GD2 directed therapies.

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