Proposal for a Quantitative 18F-FDG PET/CT Metabolic Parameter to Assess the Intensity of Bone Involvement in Multiple Myeloma

Abstract

Many efforts have been made to standardize the interpretation of 18 f-fDG pet/ct in multiple myeloma (MM) with qualitative visual analysis or with quantitative metabolic parameters using various methods for lesion segmentation of PET images. The aim of this study was to propose a quantitative method for bone and bone marrow evaluation of 18 F-FDG PET/CT considering the extent and intensity of bone 18 F-FDG uptake: Intensity of Bone Involvement (IBI). Whole body 18 F-FDG PET/CT of 59 consecutive MM patients were evaluated. Compact bone tissue was segmented in PET images using a global threshold for HU of the registered CT image. A whole skeleton mask was created and the percentage of its volume with 18 F-FDG uptake above hepatic uptake was calculated (Percentage of Bone Involvement -PBI). IBI was defined by multiplying PBI by mean SUV above hepatic uptake. IBI was compared with visual analysis performed by two experienced nuclear medicine physicians. IBI calculation was feasible in all images (range:0.00-1.35). Visual analysis categorized PET exams into three groups (negative/ mild, moderate and marked bone involvement), that had different ranges of IBI (multi comparison analysis, p < 0.0001). There was an inverse correlation between the patients' hemoglobin values and IBI (r = −0.248;p = 0.02). IBI score is an objective measure of bone and bone marrow involvement in MM, allowing the categorization of patients in different degrees of aggressiveness of the bone disease. The next step is to validate IBI in a larger group of patients, before and after treatment and in a multicentre setting.Lytic bone lesions are reported in approximately 80% of myeloma multiple (MM) patients 1,2 . Early and precise evaluation of bone involvement is crucial for staging and correct disease management.Hybrid image of positron emission tomography with 18 F-fluordeoxyglucose and computed tomography ( 18 F-FDG PET/CT) is one of the main methods for the evaluation of MM patients. It allows whole-body images, intra and extramedullary lesion detection, distinction between active lesions and scar or necrotic tissue and has been more sensitive than MRI in treatment assessment 3-5 .Many efforts have been attempted to standardize the interpretation of 18 F-FDG PET/CT in MM, using qualitative visual analysis or quantitative metabolic parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) 6-9 . However, none of these methods have been extensively used in clinical practice or research projects, probably because of the complexity of the visual quantification 6,7 or due to the lack of standardization of MTV and TLG calculations 8-10 . Also, MTV and TLG only consider areas visually defined as lesions and ignore diffuse uptake of the bone marrow.

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

“…In addition, there is still a need for the standardization of segmentation methods when calculating TMTV. In the present study, it was decided to segment individually by an absolute or a relative threshold instead of employing a global threshold of the CT image, as described by Takahashi et al [23] or a fixed threshold of 40% of SUVmax as described by Fonti et al [24]. In our experience, the use of a fixed cut-off value does not necessarily work for all patients, especially when focal disease is present or double tracer studies are carried out ( Figure S1).…”

99mTc-sestamibi SPECT/CT and 18F-FDG-PET/CT have similar performance but different imaging patterns in newly diagnosed multiple myeloma

“…This is at least partially explained by the fact that bone marrow is part of the normal biodistribution of FDG [ 28 , 29 ]. Quantitative methods have been proposed to overcome this issue, but still with some complexity for routine use [ 30 , 31 ]. Bone marrow is not part of the normal biodistribution of MIBI [ 28 ] and, as suggested by the present study, it seems to be a good alternative for assessing bone marrow involvement by multiple myeloma.…”

Metabolic Reprogramming Induces Immune Cell Dysfunction in the Tumor Microenvironment of Multiple Myeloma

“…In contrast to the reliance on oxidative phosphorylation (OXPHOS) to obtain energy in normal cells, most cancer cells adapted to their microenvironment rely heavily on aerobic glycolysis, converting glucose into lactic acid, for rapid production of adenosine triphosphate (ATP) to provide competitive advantages to cancer cells, thus meeting the requirements of rapid division and growth. This phenomenon is known as the Warburg effect ( 6 ), which is a hallmark of cancers, and is utilized in the 18F-fluorodeoxyglucose PET (18F- FDG–PET) as a sensitive diagnostic and prognostic tool in clinic ( 7 , 8 ). MM is also reported to be dependent on glycolysis due to an elevated glycolytic gene profile, as well as its susceptibility to glycolysis inhibitors, such as inhibitors of glucose transporter (GLUT) and key glycolytic enzyme ( 9 ).…”