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Purpose: The aim of this study was to compare [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 PET/CT image findings in patients with multiple myeloma (MM)., Methods: Twenty consecutive patients with symptomatic biopsy-proven MM were submitted to whole body [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 PET/CT with a time interval of 1-8 days between procedures. All lesions were counted and had their maximum SUV (SUVmax) measured. Intra-class correlation (ICC) was used to assess the agreement between [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 PET/CT findings., Results: A total of 266 lesions were detected in 19/20 patients. [ 18 F]FDG detected 223/266 (84%) lesions in 17 patients and [ 68 Ga]Ga-PSMA-11 190/266 (71%) lesions in 19 patients. Both procedures did not identify any active lesion in 1 patient. Forty-three (16%) lesions were detected only by [ 68 Ga]Ga-PSMA-11 and 76 (29%) only by [ 18 F]FDG. Both tracers identified 147 (55%) lesions. Intralesional mismatch of FDG-PSMA uptake was identified in 25 of these 147 lesions, found in 8 different patients. Different lesions with uptake of only [ 18 F]FDG or [ 68 Ga]Ga-PSMA-11 in the same patient were found in 4 patients. The highest SUVmax of [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 had a median (min-max) SUVmax of 6.5 (2.0-37.8) and 5.5 (1.7-51.3), respectively. [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 respectively identified 18 and 19 soft tissue lesions. False-positive [ 18 F]FDG findings had minimal or no uptake of [ 68 Ga]Ga-PSMA-11. Good reliability (ICC ≥ 0.75) was found for number of lesions, number of soft tissue lesions and highest SUVmax in each patient., Conclusion: [ 18 F]FDG or [ 68 Ga]Ga-PSMA-11 alone can detect most MM lesions. Almost half of the lesions take up only one of the tracers, reflecting increased glycolysis or angiogenesis in specific lesions, and suggesting their possible complementary role in MM. The marked [ 68 Ga]Ga-PSMA-11 uptake in some cases raises the possibility of a theranostic approach in selected patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The parameter intensity of bone involvement (IBI) was recently proposed to quantitatively assess patients with multiple myeloma using 18F-fluorodeoxyglucose-PET combined with computed tomography (18F-FDG PET/CT) images. Here, we aimed to calculate IBI variation (ΔIBI) 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 18F-FDG PET/CT performed to assess the outcomes of 29 patients diagnosed with multiple myeloma were retrospectively evaluated. ΔIBI 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 ΔIBI was -1.27 and the highest was 0.29. PET-remission was related to ΔIBI <0 (median = -0.10; -1.27 to +0.03), while PET-progression was related to ΔIBI >0 (median = 0.02; -0.07 to +0.29). ΔIBI around zero was found in images classified as PET-stable (median = 0.00; -0.08 to +0.06). Significant difference in ΔIBI 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 18F-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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: F-fluorodeoxiglucose (F-FDG)-PET/CT has been widely used to evaluate multiple myeloma. Tc-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 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 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.

Purpose: Quantifications in nuclear medicine are occasionally limited by the lack of standardization for defining volumes of interest (VOIs) on functional images. In the present article, we propose the use of computed tomography (CT)-based skeletal segmentation to determine anatomically the VOI in order to calculate quantitative parameters of fluorine 18 fluorodeoxyglucose (F-FDG) PET/CT images from patients with multiple myeloma., Methods: We evaluated 101 whole-body F-FDG PET/CTs of 58 patients with multiple myeloma. An initial subjective visual analysis of the PET images was used to classify the bone involvement as negative/mild, moderate, or marked. Then, a fully automated CT-based segmentation of the skeleton was performed on PET images. The maximum, mean, and SD of the standardized uptake values (SUVmax, SUVmean, and SDSUV) were calculated for bone tissue and compared with the visual analysis., Results: Forty-five (44.5%), 32 (31.7%), and 24 (23.8%) PET images were, respectively, classified as negative/mild, moderate, or marked bone involvement. All quantitative parameters were significantly related to the visual assessment of bone involvement. This association was stronger for the SUVmean [odds ratio (OR): 10.52 (95% confidence interval (CI), 5.68-19.48); P < 0.0001] and for the SDSUV [OR: 5.58 (95% CI, 3.31-9.42); P < 0.001) than for the SUVmax [OR: 1.01 (95% CI, 1.003-1.022); P = 0.003]., Conclusion: CT-based skeletal segmentation allows for automated and therefore reproducible calculation of PET quantitative parameters of bone involvement in patients with multiple myeloma. Using this method, the SUVmean and its respective SD correlated better with the visual analysis of F-FDG PET images than SUVmax. Its value in staging and evaluating therapy response needs to be evaluated.

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.

Introduction: CD34(+) cells collected for autologous bone marrow transplantation (BMT) are usually quantified in the apheresis product after collection, but the necessity to repeat these measures post-thaw is controversial., Methods: We examined the loss of CD34(+) cells after collection, preparation for freezing and post-thaw in apheresis products collected for BMT., Results: Median number of CD34(+) cells collected per unit was 1.61×10(6)/kg, viability: 97-100%. This number decreased to 1.38×10(6)/kg, viability: 96-100% before freezing and was 1.17×10(6)/kg post-thaw. Viability decreased to 86-98%. The relative loss of viable PBHPC showed an inverse correlation with the ratio "CD34(+) cells/total nucleated cells" (r=-0.45; p=<0.0005). This relative loss was largest in patients with Hodgkin's lymphoma., Conclusion: Cryopreservation and thawing of PBHPCs in leukapheresis products provokes a small but significant stem cell loss. So, quantification of viable CD34(+) cells post-thaw is important, especially in poorly mobilizing patients. Besides, the ratio "CD34(+) cells/total nucleated cells" after leukapheresis is an important parameter for prediction of neutrophil recovery after BMT., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n = 52) or dexamethasone with thalidomide (arm B; n = 56; 200 mg daily) for 12 months or until disease progression. After a median follow-up of 27 months, an intention to treat analysis showed a 2-year progression-free survival (PFS) of 30% in arm A (95% CI 22-38) and 64% in arm B (95% CI 57-71; P = 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P = 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P = 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: The use of computerized image analysis for the study of nuclear texture features has provided important prognostic information for several neoplasias. Recently fractal characteristics of the chromatin structure in routinely stained smears have shown to be independent prognostic factors in acute leukemia. In the present study we investigated the influence of the fractal dimension (FD) of chromatin on survival of patients with multiple myeloma., Methodology: We analyzed 67 newly diagnosed patients from our Institution treated in the Brazilian Multiple Myeloma Study Group. Diagnostic work-up consisted of peripheral blood counts, bone marrow cytology, bone radiograms, serum biochemistry and cytogenetics. The International Staging System (ISS) was used. In every patient, at least 40 digital nuclear images from diagnostic May-Grünwald-Giemsa stained bone marrow smears were acquired and transformed into pseudo-3D images. FD was determined by the Minkowski-Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R(2) values in the log-log plots. The influence of diagnostic features on overall survival was analyzed in Cox regressions. Patients that underwent autologous bone marrow transplantation were censored at the day of transplantation., Principal Findings: Median age was 56 years. According to ISS, 14% of the patients were stage I, 39% were stage II and 47% were stage III. Additional features of a bad prognosis were observed in 46% of the cases. When stratifying for ISS, both FD and its goodness-of-fit were significant prognostic factors in univariate analyses. Patients with higher FD values or lower goodness-of-fit showed a worse outcome. In the multivariate Cox-regression, FD, R(2), and ISS stage entered the final model, which showed to be stable in a bootstrap resampling study., Conclusions: Fractal characteristics of the chromatin texture in routine cytological preparations revealed relevant prognostic information in patients with multiple myeloma.

We tested whether the polymorphisms of the methylenetetrahydrofolate reductase gene, MTHFR C677T and A1298C, the methionine synthase gene, MTR A2756G, the methionine synthase reductase gene, MTRR A66G, and the thymidylate synthase gene, TYMS 2R-->3R, involved in folate and methionine metabolism, altered the risk for multiple myeloma (MM). Genomic DNA from 123MM patients and 188 controls was analysed by polymerase chain reaction and restriction digestion for the polymorphism analyses. The frequency of the MTR 2756 AG plus GG genotype was higher in patients than in controls (39.8% versus 23.4%, P=0.001). Individual carriers of the variant allele G had a 2.31 (95% CI: 1.38-3.87)-fold increased risk for MM compared with others. In contrast, similar frequencies of the MTHFR, the MTRR and the TYMS genotypes were seen in patients and controls. These results suggest, for the first time, a role for the MTR A2756G polymorphism in MM risk in our country, but should be confirmed by large-scale epidemiological studies with patients and controls age matched.

The GSTM1 and GSTT1 genes reduce the effects of exposure to cytotoxic agents. Both genes have a null variant allele in which the entire gene is absent. On the other hand, a common polymorphism of the tumour suppressor P53 gene results in either arginine (A) or proline (P) at amino-acid position 72. The A and P alleles code proteins with distinct functions in apoptosis and DNA repair and have been associated with variable risks for several cancers. However, their roles in multiple myeloma (MM) are still unknown. We tested in study whether the GSTM1, GSTT1 and P53 genotypes altered the risk for MM in Brazilian patients. Genomic DNA from 106 patients and 230 controls were analysed by polymerase chain reaction-based methods for identification of the genotypes. Similar frequencies of the GSTM1, GSTT1 and P53 genotypes were seen in patients and controls. Individuals with the distinct genotypes had similar risks for disease. In contrast, an excess of the GSTM1 null (45.1 vs 17.2%, P = 0.009), the P53 PP+AP (70.4 vs 44.8%, P = 0.041) and the GSTM1 null plus P53 PP+AP (29.6 vs 10.3%, P = 0.004) genotypes were seen in MM patients at stage III compared with those at stages I + II. Our data suggest that the GSTM1, GSTT1 and P53 genotypes do not influence the risk for MM. However, the inherited presence of the variant codon 72 P53 allele, described here for the first time, and the absence of the GSTM1 detoxification pathway, seem to act in disease progression in our country.

Purpose: The aim of this study was to compare [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT image findings in patients with multiple myeloma (MM). Methods: Twenty consecutive patients with symptomatic biopsy-proven MM were submitted to whole body [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT with a time interval of 1–8 days between procedures. All lesions were counted and had their maximum SUV (SUVmax) measured. Intra-class correlation (ICC) was used to assess the agreement between [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT findings. Results: A total of 266 lesions were detected in 19/20 patients. [18F]FDG detected 223/266 (84%) lesions in 17 patients and [68Ga]Ga-PSMA-11 190/266 (71%) lesions in 19 patients. Both procedures did not identify any active lesion in 1 patient. Forty-three (16%) lesions were detected only by [68Ga]Ga-PSMA-11 and 76 (29%) only by [18F]FDG. Both tracers identified 147 (55%) lesions. Intralesional mismatch of FDG-PSMA uptake was identified in 25 of these 147 lesions, found in 8 different patients. Different lesions with uptake of only [18F]FDG or [68Ga]Ga-PSMA-11 in the same patient were found in 4 patients. The highest SUVmax of [18F]FDG and [68Ga]Ga-PSMA-11 had a median (min–max) SUVmax of 6.5 (2.0–37.8) and 5.5 (1.7–51.3), respectively. [18F]FDG and [68Ga]Ga-PSMA-11 respectively identified 18 and 19 soft tissue lesions. False-positive [18F]FDG findings had minimal or no uptake of [68Ga]Ga-PSMA-11. Good reliability (ICC ≥ 0.75) was found for number of lesions, number of soft tissue lesions and highest SUVmax in each patient. Conclusion: [18F]FDG or [68Ga]Ga-PSMA-11 alone can detect most MM lesions. Almost half of the lesions take up only one of the tracers, reflecting increased glycolysis or angiogenesis in specific lesions, and suggesting their possible complementary role in MM. The marked [68Ga]Ga-PSMA-11 uptake in some cases raises the possibility of a theranostic approach in selected patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]