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Agradecimentos: This study was funded by (1) Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (grant numbers 2018/14132-0 and 2021/03421-3); (2) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil—CAPES (finance code 001); and (3) Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (grant number 311841/2018-0) Abstract: Multiple myeloma (MM) accounts for 10-15% of all hematologic malignancies, as well as 20% of deaths related to hematologic malignant tumors, predominantly affecting bone and bone marrow. Positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (FDG-PET/CT) is an important method to assess the tumor burden of these patients. It is often challenging to classify the extent of disease involvement in the PET scans for many of these patients because both focal and diffuse bone lesions may coexist, with varying degrees of FDG uptake. Different metrics involving volumetric parameters and texture features have been proposed to objectively assess these images. Here, we review some metabolic parameters that can be extracted from FDG-PET/CT images of MM patients, including technical aspects and predicting MM outcome impact. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters known to be independent predictors of MM outcome. However, they have not been adopted in clinical practice due to the lack of measuring standards. CT-based segmentation allows automated, and therefore reproducible, calculation of bone metabolic metrics in patients with MM, such as maximum, mean and standard deviation of the standardized uptake values (SUV) for the entire skeleton. Intensity of bone involvement (IBI) is a new parameter that also takes advantage of this approach with promising results. Other indirect parameters obtained from FDG-PET/CT images, such as visceral adipose tissue glucose uptake and subcutaneous adipose tissue radiodensity, may also be useful to evaluate the prognosis of MM patients. Furthermore, the use and quantification of new radiotracers can address different metabolic aspects of MM and may have important prognostic implications FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto

Agradecimentos: The authors would like to thank the Nuclear and Energy Research Institute (IPEN-CNEN), Sao Paulo, Brazil for supplying the radiopharmaceuticals used in the present project [IPEN/UNICAMP agreement No. 01342000458/2017-15]. The authors are grateful for the financial support from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [grant numbers 2009/54065-0, 2018/00654-4]. This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) [Finance Code 001] Abstract: Purpose The parameter intensity of bone involvement (IBI) was recently proposed to quantitatively assess patients with multiple myeloma using F-18-fluorodeoxyglucose-PET combined with computed tomography (F-18-FDG PET/CT) images. Here, we aimed to calculate IBI variation (Delta IBI) between two consecutive PET/CT of the same patient and verified its relationship with a subjective visual analysis of the images and with clinical outcome. Methods Consecutive whole-body F-18-FDG PET/CT performed to assess the outcomes of 29 patients diagnosed with multiple myeloma were retrospectively evaluated. Delta IBI was calculated after bone segmentation, using liver standardized uptake value as a threshold to determine metabolically active volumes in the skeleton. For each pair of consecutive PET/CTs, two nuclear medicine physicians classified visually the most recent image as PET-remission, PET-progression or PET-stable when compared to the previous examination. Results The lowest Delta IBI was -1.27 and the highest was 0.29. PET-remission was related to Delta IBI 0 (median = 0.02; -0.07 to +0.29). Delta IBI around zero was found in images classified as PET-stable (median = 0.00; -0.08 to +0.06). Significant difference in Delta IBI was found between the three groups. Multivariate stepwise analysis showed that IBI value at diagnostic PET/CT, serum calcium and percentage of plasma cells in the bone marrow are independent prognostic factors. Conclusion Delta IBI provides quantitative data for variations of F-18-FDG uptake in the bone marrow during the follow-up of the patients. In addition, higher IBI values at diagnosis are associated with a higher risk of patient's death FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES Fechado

Agradecimentos: We thank the Nuclear and Energy Research Institute (IPEN-CNEN) São Paulo, Brazil, for kindly supplying radiopharmaceuticals used in the present project (IPEN/UNICAMP agreement No. 01342000458/2017-15). We are grateful for financial support from FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo), grant numbers 2009/54065-0 and 2018/00654-4. This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. CDR has a research grant from CNPq (National Council of Research) proc 311841/2018-0. ILM has a research grant from CNPq (National Council of Research) proc 305110/2018-7. This study was funded by (1) Energy Research Institute – IPEN, São Paulo, Brazil, (IPEN/UNICAMP agreement No. 01342000458/2017-15); (2) Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (grant numbers 2009/54065-0, 2018/14132-0 and 2018/00654-4); (3) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil – CAPES (finance code 001); and (4) Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (grant number 311841/2018-0) Abstract: Purpose F-18-fluorodeoxiglucose (F-18-FDG)-PET/CT has been widely used to evaluate multiple myeloma.Tc-99m-sestamibi (MIBI) scintigraphy has also been proposed for assessing multiple myeloma, but its use with state-of-the-art single-photon emission computed tomography/computed tomography (SPECT/CT) technology has not been fully evaluated.This study aimed to compare these two imaging modalities in multiple myeloma staging. Materials and methods Sixty-two patients with recently diagnosed multiple myeloma were submitted to whole-body(18)F-FDG-PET/CT and whole-body MIBI scans plus SPECT/CT of the chest and abdomen/pelvis. Number of focal lesions, contiguous soft tissue involvement (CSTI), extramedullary lesions (EMLs) and diffuse bone marrow (BM) involvement were recorded. Results PET/CT was positive in 59 patients (95%) and MIBI SPECT/CT in 58 (93%) (P = 0.69). MIBI detected more diffuse bone marrow involvement than PET/CT (respectively 78 vs. 58% of the patients), while PET/CT demonstrated more focal lesions than MIBI SPECT/CT (81 vs. 54% of the patients) (P = 0.002). PET/CT detected EMLs in four subjects and MIBI in one subject. CSTI was found in 28 (45%) and 23 (37%) patients on PET/CT and MIBI images, respectively (P = 0.36). Three patients with lytic lesions and no FDG uptake were MIBI positive, and two subjects with lytic lesions without MIBI uptake were FDG positive. Conclusion MIBI SPECT/CT performs similarly to(18)F-FDG-PET/CT in identifying sites of active disease in multiple myeloma staging. MIBI is more efficient than FDG for detecting the diffuse involvement of bone marrow but less efficient for detecting focal lesions. Some patients presented a 'mismatch' pattern of FDG/MIBI uptake FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto