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PET/CT in Multiple Myeloma Patients

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 41448

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Dr. Caroline Bodet-Milin

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Nantes-Angers Cancer Research Center (CRCNA), University of Nantes, Inserm UMR 892, 8 quai Moncousu, 44007 Nantes, FranceDepartment of Nuclear Medicine, CHU de Nantes, 1 place Alexis Ricordeau, 44093 Nantes, France
Interests: FDG-PET, Immuno-PET, Hematology, Multiple myeloma, Lymphoma, Theranostics, Radionuclide therapy, therapeutic evaluation, radiomics

Dr. Cristina Nanni

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Nuclear Medicine Unit, University of Bologna, S. Orsola-Malpighi Hospital Bologna, University of Bologna, 40138 Bologna, Italy
Interests: Clinical application of PET/CT with FDG and other new tracers in oncology (in particular Multiple myeloma and Prostate cancer) and inflective-inflammatory disease. Integrated morpho-functional imaging (PET/ceCT). PET/CT guided biopsy

Dr. Constantin Lapa

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Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
Interests: multiple myeloma; novel PET tracers; theranostics; radionuclide therapy
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Dear Colleagues,

Over the past decades, positron emission tomography/computed tomography (PET/CT) with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) has increasingly been used in the management of multiple myeloma and other clonal proliferative plasma cell disorders as it provides useful information on patient prognosis and is the tool of choice in treatment response assessment. In addition, new PET/CT tracers targeting different metabolic pathways (such as ¹¹C-methionine, ¹¹C-/¹⁸F-choline) or receptors expressed by multiple myeloma cells (such as C-X-C motif chemokine receptor 4) and acting as molecular imaging biomarkers have been introduced and might provide advantages over the standard ¹⁸F-FDG.

This special issue aims to provide a comprehensive overview over the use of ¹⁸F-FDG PET/CT and new tracers in patients with multiple myeloma and other plasma cell disorders, such as smouldering multiple myeloma and solitary plasmacytoma. In addition, an outlook to new analytic (radiomics), theranostic approaches (including immuno-PET) and functional MRI (including PET/MRI) will be given.

Dr. Caroline Bodet-Milin
Dr. Cristina Nanni
Dr. Constantin Lapa
Guest Editors

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Keywords

Multiple Myeloma
FDG-PET/CT
New tracers
Therapeutic evaluation
Radiomics
Immuno-PET
Theranostics
MRI

Published Papers (11 papers)

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Research

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18 pages, 3474 KiB

Open AccessArticle

Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease

by Sébastien Gouard, Catherine Maurel, Séverine Marionneau-Lambot, Delphine Dansette, Clément Bailly, François Guérard, Nicolas Chouin, Ferid Haddad, Cyril Alliot, Joëlle Gaschet, Romain Eychenne, Françoise Kraeber-Bodéré and Michel Chérel

Cancers 2020, 12(9), 2721; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12092721 - 22 Sep 2020

Cited by 10 | Viewed by 3670

Abstract

Despite therapeutic progress in recent years with the introduction of targeted therapies (daratumumab, elotuzumab), multiple myeloma remains an incurable cancer. The question is therefore to investigate the potential of targeted alpha therapy, combining an anti-CD138 antibody with astatine-211, to destroy the residual cells that cause relapses. A preclinical syngeneic mouse model, consisting of IV injection of 1 million of 5T33 cells in a KaLwRij C57/BL6 mouse, was treated 10 days later with an anti-mCD138 antibody, called 9E7.4, radiolabeled with astatine-211. Four activities of the ²¹¹At-9E7.4 radioimmunoconjugate were tested in two independent experiments: 370 kBq (n = 16), 555 kBq (n = 10), 740 kBq (n = 17) and 1100 kBq (n = 6). An isotype control was also tested at 555 kBq (n = 10). Biodistribution, survival rate, hematological parameters, enzymatic hepatic toxicity, histological examination and organ dosimetry were considered. The survival median of untreated mice was 45 days after engraftment. While the activity of 1100 kBq was highly toxic, the activity of 740 kBq offered the best efficacy with 65% of overall survival 150 days after the treatment with no evident sign of toxicity. This work demonstrates the pertinence of treating minimal residual disease of multiple myeloma with an anti-CD138 antibody coupled to astatine-211. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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10 pages, 1725 KiB

Open AccessCommunication

Glucose Metabolism Quantified by SUVmax on Baseline FDG-PET/CT Predicts Survival in Newly Diagnosed Multiple Myeloma Patients: Combined Harmonized Analysis of Two Prospective Phase III Trials

by Anne-Victoire Michaud-Robert, Elena Zamagni, Thomas Carlier, Clément Bailly, Bastien Jamet, Cyrille Touzeau, Philippe Moreau, Françoise Kraeber-Bodere, Cristina Nanni and Caroline Bodet-Milin

Cancers 2020, 12(9), 2532; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12092532 - 06 Sep 2020

Cited by 15 | Viewed by 2325

Abstract

Background: Multiple myeloma is a hematological neoplasm characterized by a clonal proliferation of malignant plasma cells in the bone marrow, and is associated with high morbidity and mortality and variable survival. Positron emission tomography combined with computed tomography using 18F-deoxyfluoroglucose (FDG-PET/CT) is a promising technique for initial staging of symptomatic multiple myeloma patients. The objective of this study was to assess the prognostic value of this technique at baseline in symptomatic multiple myeloma patients included in two large European prospective studies (French and Italian). Methods: We retrospectively performed a combined harmonized analysis of 227 newly diagnosed transplant eligible multiple myeloma patients from two separate phase III trials. All images were centrally reviewed and analyzed using visual criteria and maximal standardized uptake value. An ad-hoc approach (called modified Combat) was applied to harmonize the data and then remove the “country effect” in order to strengthen the reliability of the final conclusions. Results: Using a multivariate analysis including treatment arm, R-ISS score, presence of extra-medullary disease and bone SUVmax, only bone SUVmax (p = 0.016) was an independent prognosis factor with an OS threshold of 7.1. For PFS, treatment arm and presence of extra-medullary disease were both independent prognosis biomarkers (p = 0.022 and 0.006 respectively). Conclusions: Our results show that bone SUVmax is a simple and reliable biomarker to analyze FDG-PET/CT at baseline that strongly correlates with a poorer prognosis for MM patients. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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13 pages, 2050 KiB

Open AccessArticle

The Link between Cytogenetics/Genomics and Imaging Patterns of Relapse and Progression in Patients with Relapsed/Refractory Multiple Myeloma: A Pilot Study Utilizing 18F-FDG PET/CT

by Xiang Zhou, Alexander Dierks, Olivia Kertels, Samuel Samnick, Malte Kircher, Andreas K. Buck, Larissa Haertle, Sebastian Knorz, David Böckle, Lukas Scheller, Janin Messerschmidt, Mohammad Barakat, Marietta Truger, Claudia Haferlach, Hermann Einsele, Leo Rasche, K. Martin Kortüm and Constantin Lapa

Cancers 2020, 12(9), 2399; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12092399 - 24 Aug 2020

Cited by 4 | Viewed by 2704

Abstract

Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1–10) lines of therapy. Six (25%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUV_max) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUV_max of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUV_max of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUV_max on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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11 pages, 1243 KiB

Open AccessFeature PaperArticle

18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in Patients with Smoldering Multiple Myeloma: Imaging Pattern and Clinical Features

by Xiang Zhou, Alexander Dierks, Olivia Kertels, Malte Kircher, Andreas Schirbel, Samuel Samnick, Andreas K. Buck, Sebastian Knorz, David Böckle, Lukas Scheller, Janin Messerschmidt, Mohammad Barakat, K. Martin Kortüm, Leo Rasche, Hermann Einsele and Constantin Lapa

Cancers 2020, 12(8), 2333; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12082333 - 18 Aug 2020

Cited by 16 | Viewed by 3396

Abstract

This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV_mean) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV_mean of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR_mean) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR_mean in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR_max of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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14 pages, 2112 KiB

Open AccessArticle

Can ¹⁸F-NaF PET/CT before Autologous Stem Cell Transplantation Predict Survival in Multiple Myeloma?

by Christos Sachpekidis, Annette Kopp-Schneider, Maximilian Merz, Anna Jauch, Marc-Steffen Raab, Hartmut Goldschmidt and Antonia Dimitrakopoulou-Strauss

Cancers 2020, 12(5), 1335; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12051335 - 23 May 2020

Cited by 5 | Viewed by 6235

Abstract

There is an unmet need for positron emission tomography (PET) radiotracers that can image bone disease in multiple myeloma (MM) in a more sensitive and specific way than the widely used ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). Sodium fluoride (¹⁸F-NaF) is a highly sensitive tracer of bone reconstruction, evolving as an important imaging agent for the assessment of malignant bone diseases. We attempted to investigate for the first time the prognostic significance of ¹⁸F-NaF PET/CT in newly diagnosed, symptomatic MM patients planned for autologous stem cell transplantation (ASCT). Forty-seven patients underwent dynamic and static PET/CT with ¹⁸F-NaF before treatment. After correlation with the respective findings on CT and ¹⁸F-FDG PET/CT that served as reference, the ¹⁸F-NaF PET findings were compared with established factors of high-risk disease, like cytogenetic abnormalities as well as bone marrow plasma cell infiltration rate. Furthermore, the impact of ¹⁸F-NaF PET/CT on progression-free survival (PFS) was analyzed. Correlation analysis revealed a moderate, significant correlation of the ¹⁸F-NaF parameters SUV_average and K₁ in reference tissue with bone marrow plasma cell infiltration rate. However, no significant correlation was observed regarding all other ¹⁸F-NaF PET parameters. Survival analysis revealed that patients with a pathologic ¹⁸F-NaF PET/CT have a shorter PFS (median = 36.2 months) than those with a physiologic scan (median = 55.6 months) (p = 0.02). Nevertheless, no quantitative ¹⁸F-NaF parameter could be shown to adversely affect PFS. In contrast, the respective analysis for quantitative dynamic ¹⁸F-FDG PET/CT revealed that the parameters SUV_max, fractional blood volume (V_B), k₃ and influx from reference tissue as well as SUV_average from MM lesions had a significant negative impact on patient survival. The herein presented findings highlight the rather limited role of ¹⁸F-NaF PET/CT as a single PET approach in MM. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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12 pages, 3919 KiB

Open AccessArticle

¹⁸F-FDG and ¹¹C-Methionine PET/CT in Newly Diagnosed Multiple Myeloma Patients: Comparison of Volume-Based PET Biomarkers

by Maria I Morales-Lozano, Oliver Viering, Samuel Samnick, Paula Rodriguez-Otero, Andreas K Buck, Maria Marcos-Jubilar, Leo Rasche, Elena Prieto, K Martin Kortüm, Jesus San-Miguel, Maria J. Garcia-Velloso and Constantin Lapa

Cancers 2020, 12(4), 1042; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12041042 - 23 Apr 2020

Cited by 23 | Viewed by 4081

Abstract

¹¹C-methionine (¹¹C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of ¹¹C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to ¹⁸F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone ¹¹C-MET and ¹⁸F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion ¹¹C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), ¹¹C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in ¹¹C-MET than in ¹⁸F-FDG (p < 0.05, respectively). ¹¹C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that ¹¹C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than ¹⁸F-FDG. Its implications for prognosis evaluation need further investigation. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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10 pages, 2739 KiB

Open AccessCommunication

PET-FDG: Impetus

by Cristina Nanni

Cancers 2020, 12(4), 1030; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12041030 - 22 Apr 2020

Cited by 13 | Viewed by 5046

Abstract

The International Myeloma Working Group (IMWG)recommends FDG PET/CT (Fluoro-Deoxy-glucose Positron Emission Tomography/Computed Tomography) as the gold standard imaging modality for initial evaluation and response to therapy assessment in multiple myeloma. In fact, FDG PET/CT, provides multiple useful indexes to risk-stratify patients and has significant prognostic value. However, multiple myeloma remains a complex disease to interpret on imaging. The Italian myeloma criteria for PET use (IMPeTUs) were proposed to standardize FDG PET/CT reading in multiple myeloma. In this communication an overview on IMPeTUs is provided as well as some examples of application. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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Review

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11 pages, 1859 KiB

Open AccessReview

Whole-Body Functional MRI and PET/MRI in Multiple Myeloma

by Sébastien Mulé, Edouard Reizine, Paul Blanc-Durand, Laurence Baranes, Pierre Zerbib, Robert Burns, Refaat Nouri, Emmanuel Itti and Alain Luciani

Cancers 2020, 12(11), 3155; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113155 - 27 Oct 2020

Cited by 21 | Viewed by 4283

Abstract

Bone disease is one of the major features of multiple myeloma (MM), and imaging has a pivotal role in both diagnosis and follow-up. Whole-body magnetic resonance imaging (MRI) is recognized as the gold standard for the detection of bone marrow involvement, owing to its high sensitivity. The use of functional MRI sequences further improved the performances of whole-body MRI in the setting of MM. Whole-body diffusion-weighted (DW) MRI is the most attractive functional technique and its systematic implementation in general clinical practice is now recommended by the International Myeloma Working Group. Whole-body dynamic contrast-enhanced (DCE) MRI might provide further information on lesions vascularity and help evaluate response to treatment. Whole Body PET/MRI is an emerging hybrid imaging technique that offers the opportunity to combine information on morphology, fat content of bone marrow, bone marrow cellularity and vascularization, and metabolic activity. Whole-body PET/MRI allows a one-stop-shop examination, including the most sensitive technique for detecting bone marrow involvement, and the most recognized technique for treatment response evaluation. This review aims at providing an overview on the value of whole-body MRI, including DW and DCE MRI, and combined whole-body ¹⁸F-FDG PET/MRI in diagnosis, staging, and response evaluation in patients with MM. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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13 pages, 2104 KiB

Open AccessReview

Choline PET/CT in Multiple Myeloma

by Charles Mesguich, Cyrille Hulin, Axelle Lascaux, Laurence Bordenave, Gerald Marit and Elif Hindié

Cancers 2020, 12(6), 1394; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12061394 - 28 May 2020

Cited by 12 | Viewed by 2941

Abstract

The field of multiple myeloma (MM) imaging has evolved. The International Myeloma Working Group recently recommended performing ¹⁸F-fluorodeoxyglucose glucose (¹⁸FDG) positron emission tomography/computed tomography (PET/CT) with the aim of staging MM patients at baseline and evaluating response to therapy. Novel oncological radiotracers such as ¹¹C-Choline and ¹⁸F-Fluorocholine, have been studied in comparison with ¹⁸FDG, mostly in MM patients presenting with refractory disease or suspected relapse. Choline-based tracers may overcome some limitations of ¹⁸FDG, which include a lack of sensitivity in depicting skull lesions and the fact that 10% of MM patients are FDG-negative. The majority of MM lesions display a higher uptake of Choline than FDG. Also, in many situations, Choline may offer better lesion visualization, with a higher tumor to background ratio; however, various patterns of Choline and FDG uptake have been observed in MM and some limitations, notably as regards liver lesions, should be recognized. Overall, Choline may provide additional detection of up to 75% more lesions. This article aims to provide a comprehensive review of the potential role of Choline in multiple myeloma, as compared to FDG, encompassing Choline physiopathology as well as data from clinical studies. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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11 pages, 2349 KiB

Open AccessReview

FDG-PET/CT, a Promising Exam for Detecting High-Risk Myeloma Patients?

by Anne-Victoire Michaud-Robert, Bastien Jamet, Clément Bailly, Thomas Carlier, Philippe Moreau, Cyrille Touzeau, Mickael Bourgeois, Françoise Kraeber-Bodere and Caroline Bodet-Milin

Cancers 2020, 12(6), 1384; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12061384 - 28 May 2020

Cited by 5 | Viewed by 2360

Abstract

Multiple myeloma (MM) is a haematological neoplasm characterized by a clonal proliferation of malignant plasma cells in the bone marrow. MM is associated with high morbidity and mortality and variable survival, which can be very short for some patients but over 10 years for others. These differences in survival are explained by intra- and inter-tumoral heterogeneity and demonstrate the potential benefits of adapting the treatment course for high-risk patients with a poorer prognosis. Indeed, identification of these high-risk patients is necessary and is based on the identification of high-risk biomarkers including clinical variables, genomics and imaging results. Positron emission tomography combined with computed tomography using 18F-deoxyfluoroglucose (FDG-PET/CT) is a reliable technique for the initial staging of patients with symptomatic multiple myeloma (MM), and has been included in the IMWG (International Myeloma Working Group) recommendations in 2019. According to clinical studies, FDG-PET/CT characteristics could be used to define high-risk patients at initial diagnosis of symptomatic MM. The goal of this review is to demonstrate the prognostic value of FDG-PET in symptomatic MM patients, particularly in identifying high-risk patients, and thus, to best adapt therapeutic management in the future. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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Other

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17 pages, 1088 KiB

Open AccessPerspective

ImmunoPET in Multiple Myeloma—What? So What? Now What?

by Clément Bailly, Benjamin Chalopin, Sébastien Gouard, Thomas Carlier, Patricia Remaud-Le Saëc, Séverine Marionneau-Lambot, Philippe Moreau, Cyrille Touzeau, Françoise Kraeber-Bodere, Caroline Bodet-Milin and Michel Chérel

Cancers 2020, 12(6), 1467; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12061467 - 04 Jun 2020

Cited by 7 | Viewed by 2560

Abstract

Despite constant progress over the past three decades, multiple myeloma (MM) is still an incurable disease, and the identification of new biomarkers to better select patients and adapt therapy is more relevant than ever. Recently, the introduction of therapeutic monoclonal antibodies (mAbs) (including direct-targeting mAbs and immune checkpoint inhibitors) appears to have changed the paradigm of MM management, emphasizing the opportunity to cure MM patients through an immunotherapeutic approach. In this context, immuno-positron emission tomography (immunoPET), combining the high sensitivity and resolution of a PET camera with the specificity of a radiolabelled mAb, holds the capability to cement this new treatment paradigm for MM patients. It has the potential to non-invasively monitor the distribution of therapeutic antibodies or directly monitor biomarkers on MM cells, and to allow direct observation of potential changes over time and in response to various therapeutic interventions. Tumor response could, in the future, be anticipated more effectively to provide individualized treatment plans tailored to patients according to their unique imaging signatures. This work explores the important role played by immunotherapeutics in the management of MM, and focuses on some of the challenges for this drug class and the significant interest of companion imaging agents such as immunoPET. Full article

(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)

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