Antonia Dimitrakopoulou-Strauss
Christos Sachpekidis
Constantin Lapa- 1Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany
- 2Department of Nuclear Medicine, University of Augsburg, Augsburg, Germany
Editorial on Research Topic
Molecular Imaging in Multiple Myeloma: An Update and Future Perspectives
Multiple myeloma (MM) is the second most common hematologic malignancy after non-Hodgkin lymphoma accounting for approximately 1% of neoplastic diseases. MM is not curable despite the progress in diagnostic procedures and therapeutic approaches. Though still considered an incurable disease, its prognosis has been continuously improving since the ‘90s due to new therapies, including immunomodulators, proteasome inhibitors and monoclonal antibodies. Nowadays, MM can be classified as a chronic disease (1). In terms of imaging, modern diagnostic and staging modalities include computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/CT (PET/CT), mainly with the radiotracer 18F-FDG. 18F-FDG PET imaging has nowadays a great impact on the diagnostics and management of oncological patients and has gained increasing use worldwide (2). On the other hand, despite being a valuable tool in diagnosis, prognosis and therapy monitoring, 18F-FDG PET/CT has some limitations including a non-negligible rate of false-negative and false-positive findings in patients with MM (3, 4).
In this Research Topic Mesguich et al. present in an interesting review the strengths and limitations of both molecular hybrid imaging techniques, PET/CT and PET/MRI, for the diagnosis and therapy monitoring in MM. In particular, the role of 18F-FDG PET/CT in the diagnosis, staging, prognosis and monitoring of treatment response, also including new therapeutic protocols like immunomodulatory drugs and proteasome inhibitors, are discussed and compared to other imaging modalities, such as MRI and diffusion-weighted MRI (DW-MRI). Overall, DW-MRI has a high sensitivity for bone marrow involvement, whereas baseline 18F-FDG PET carries a strong prognostic value and a strong association with relapse risk and survival. Both imaging modalities 18F-FDG PET/CT and DW-MRI are crucial for the detection of extramedullary and paramedullary myeloma manifestations. Longitudinal 18F-FDG PET/CT studies are superior to MRI and DW-MRI for the evaluation of treatment response, since they provide an earlier assessment of post-therapeutic changes and prognosis with (even in the absence of standardized reading) a negative 18F-FDG PET/CT scan being associated with a longer PFS (Mesguich et al.). More studies are needed to address the role of novel therapies involving antibodies, antibody–drug conjugates, bispecific antibodies, and chimeric antigen receptor (CAR) T cells as mentioned by Mesguich et al. In the setting of response evaluation, both bone marrow-based minimal residual disease (MRD) diagnostics and 18F-FDG PET seem to have a complementary role meaning that double-negative patients demonstrate a longer PFS as compared to either MRD or 18F-FDG PET positive findings (Mesguich et al.) (5).
The role of several, non-18F-FDG radiopharmaceuticals is presented in another review by von Hinten et al. The authors discuss the impact of C-X-C motif chemokine receptor 4 (CXCR-4) imaging with 68Ga-Pentixafor, amino acid imaging with 11C-Methionine and 11C-Choline, proliferation imaging with 18F-FLT and imaging of bone remodeling with 18F-NaF. This review demonstrates the potential of Pentixafor also for theranostic approaches in MM using the combination of 68Ga-Pentixafor for selection of patients and 177Lu-Pentixafor for therapy (6). The value of labeled amino acids, in particular 11C-Methionine and the proliferation tracer 18F-FLT is topic of another review by Minamimoto. Both reviews demonstrate some advantages of these non-FDG tracers and show the complementary role to 18F-FDG, in particular in 18F-FDG-negative myeloma lesions. Main limitation of these non 18F-FDG tracers is the lack of studies in larger patient cohorts (7).
In conclusion, and contemplating the future of molecular imaging, the combination of fourth generation PET/CT scanners with extended field of view, which provide higher sensitivity, faster scanning protocols, application of less tracer activities, and more sophisticated reconstruction and image evaluation algorithms based on artificial intelligence approaches, will further improve diagnosis and therapy monitoring with PET/CT in MM (8). New dedicated tracers which may complement 18F-FDG in combination to MRD diagnostics, and/or sequencing of tumor probes, including whole genome sequencing, RNA sequencing, exome sequencing and gene expression, will provide a more holistic approach for the characterization of MM patients in the near future for both diagnosis and treatment response assessment and will allow personalized therapeutic approaches.
Author Contributions
CL and CS: editing of manuscript. AD-S: writing of manuscript. All authors contributed to the article and approved the submitted version.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
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2. Dimitrakopoulou-Strauss A. PET-based molecular imaging in personalized oncology: potential of the assessment of therapeutic outcome. Future Oncology. (2015) 5:127–42. doi: 10.2217/fon.15.28
3. Sachpekidis C, Goldschmidt H, Hose D, Pan L, Cheng C, Kopka K, et al. PET/CT studies of multiple myeloma using (18) F-FDG and (18) F-NaF: comparison of distribution patterns and tracers' pharmacokinetics. Eur J Nucl Med Mol Imaging. (2014) 41:1343–53. doi: 10.1007/s00259-014-2721-y
4. Sachpekidis C, Goldschmidt H, Dimitrakopoulou-Strauss A. Positron emission tomography (PET) radiopharmaceuticals in multiple myeloma. Molecules. (2019) 25:134. doi: 10.3390/molecules25010134
5. Moreau P, Attal M, Caillot D, Macro M, Karlin L, Garderet L, et al. Prospective evaluation of magnetic resonance imaging and [(18)F]Fluorodeoxyglucose positron emission tomography-computed tomography at diagnosis and before maintenance therapy in symptomatic patients with multiple myeloma included in the IFM/DFCI (2009). Trial: results of the IMAJEM study. J Clin Oncol. (2017) 35:2911–8. doi: 10.1200/JCO.2017.72.2975
6. Buck AK, Haug A, Dreher N, Lambertini A, Higuchi T, Lapa C, et al. Imaging of C-X-C motif chemokine receptor 4 expression in 690 patients with solid or hematologic neoplasms using 68 Ga-PentixaFor PET. Nucl Med. (2022) jnumed.121.263693. doi: 10.2967/jnumed.121.263693
7. Lapa C, Kircher M, Da Via M, Schreder M, Rasche L, Kortüm KM, et al. Comparison of 11C-choline and 11C-methionine PET/CT in multiple myeloma. Clin Nucl Med. (2019) 44:620–4. doi: 10.1097/RLU.0000000000002638
Keywords: multiple myeloma, PET/CT, PET-MRI, therapy diagnosis, therapy monitoring, prognosis
Citation: Dimitrakopoulou-Strauss A, Sachpekidis C and Lapa C (2022) Editorial: Molecular Imaging in Multiple Myeloma: An Update and Future Perspectives. Front. Nucl. Med. 2:904502. doi: 10.3389/fnume.2022.904502
Received: 25 March 2022; Accepted: 31 March 2022;
Published: 25 April 2022.
Edited and reviewed by: Mario Petretta, IRCCS SYNLAB SDN, Italy
Copyright © 2022 Dimitrakopoulou-Strauss, Sachpekidis and Lapa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Antonia Dimitrakopoulou-Strauss, a.dimitrakopoulou-strauss@dkfz.de