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Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18F-FDG and 18F-FLT PET/CT imaging.

ABSTRACT: BACKGROUND:Despite the significant upgrading in recent years of the role of 18F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3'-Deoxy-3'-[18F]fluorothymidine (18F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate 18F-FLT PET/CT in imaging of MM patients, in the context of its combined use with 18F-FDG PET/CT. RESULTS:Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent 18F-FDG PET/CT and 18F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. 18F-FDG PET/CT demonstrated focal, 18F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, 18F-FLT PET/CT showed focal, 18F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 18F-FDG avid, focal, MM-indicative lesions were detected with 18F-FDG PET/CT, while 17 18F-FLT avid, focal, MM-indicative lesions were detected with 18F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for 18F-FDG PET/CT than for 18F-FLT PET/CT. A common finding was a mismatch of focally increased 18F-FDG uptake and reduced 18F-FLT uptake (lower than the surrounding bone marrow). Moreover, 18F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUVmean and SUVmax were significantly higher for 18F-FLT than for 18F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in reference bone marrow for both tracers. CONCLUSIONS:Despite the limited number of patients analyzed in this pilot study, the first results of the trial indicate that 18F-FLT does not seem suitable as a single tracer in MM diagnostics. Further studies with a larger patient population are warranted to generalize the herein presented results.

SUBMITTER: Sachpekidis C

PROVIDER: S-EPMC5891438 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18F-FDG and 18F-FLT PET/CT imaging.

Sachpekidis C C Goldschmidt H H Kopka K K Kopp-Schneider A A Dimitrakopoulou-Strauss A A

EJNMMI research 20180410 1

<h4>Background</h4>Despite the significant upgrading in recent years of the role of 18F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3'-Deoxy-3'-[18F]fluorothymidine (18F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate 18F-FLT PET/CT in imaging of MM patients, in the co ...[more]

PMID: 29633046

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Project description:PurposeThe purpose of this study was to explore the application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) image radiomics in the identification of spine multiple myeloma (MM) and bone metastasis (BM), and whether this method could improve the classification diagnosis performance compared with traditional methods.MethodsThis retrospective study collected a total of 184 lesions from 131 patients between January 2017 and January 2021. All images were visually evaluated independently by two physicians with 20 years of experience through the double-blind method, while the maximum standardized uptake value (SUVmax) of each lesion was recorded. A total of 279 radiomics features were extracted from the region of interest (ROI) of CT and PET images of each lesion separately by manual method. After the reliability test, the least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation were used to perform dimensionality reduction and screening of features. Two classification models of CT and PET were derived from CT images and PET images, respectively and constructed using the multivariate logistic regression algorithm. In addition, the ComModel was constructed by combining the PET model and the conventional parameter SUVmax. The performance of the three classification diagnostic models, as well as the human experts and SUVmax, were evaluated and compared, respectively.ResultsA total of 8 and 10 features were selected from CT and PET images for the construction of radiomics models, respectively. Satisfactory performance of the three radiomics models was achieved in both the training and the validation groups (Training: AUC: CT: 0.909, PET: 0.949, ComModel: 0.973; Validation: AUC: CT: 0.897, PET: 0.929, ComModel: 0.948). Moreover, the PET model and ComModel showed significant improvement in diagnostic performance between the two groups compared to the human expert (Training: P = 0.01 and P = 0.001; Validation: P = 0.018 and P = 0.033), and no statistical difference was observed between the CT model and human experts (P = 0.187 and P = 0.229, respectively).ConclusionThe radiomics model constructed based on 18F-FDG PET/CT images achieved satisfactory diagnostic performance for the classification of MM and bone metastases. In addition, the radiomics model showed significant improvement in diagnostic performance compared to human experts and PET conventional parameter SUVmax.

Project description:BackgroundNon-invasive imaging biomarkers of cellular proliferation hold great promise for quantifying response to personalized medicine in oncology. An emerging approach to assess tumor proliferation utilizes the positron emission tomography (PET) tracer 3'-deoxy-3'[(18)F]-fluorothymidine, [(18)F]-FLT. Though several studies have associated serial changes in [(18)F]-FLT-PET with elements of therapeutic response, the degree to which [(18)F]-FLT-PET quantitatively reflects proliferative index has been continuously debated for more that a decade. The goal of this study was to elucidate quantitative relationships between [(18)F]-FLT-PET and cellular metrics of proliferation in treatment naïve human cell line xenografts commonly employed in cancer research.Methods and findings[(18)F]-FLT-PET was conducted in human cancer xenograft-bearing mice. Quantitative relationships between PET, thymidine kinase 1 (TK1) protein levels and immunostaining for proliferation markers (Ki67, TK1, PCNA) were evaluated using imaging-matched tumor specimens. Overall, we determined that [(18)F]-FLT-PET reflects TK1 protein levels, yet the cell cycle specificity of TK1 expression and the extent to which tumors utilize thymidine salvage for DNA synthesis decouple [(18)F]-FLT-PET data from standard estimates of proliferative index.ConclusionsOur findings illustrate that [(18)F]-FLT-PET reflects tumor proliferation as a function of thymidine salvage pathway utilization. Unlike more general proliferation markers, such as Ki67, [(18)F]-FLT PET reflects proliferative indices to variable and potentially unreliable extents. [(18)F]-FLT-PET cannot discriminate moderately proliferative, thymidine salvage-driven tumors from those of high proliferative index that rely primarily upon de novo thymidine synthesis. Accordingly, the magnitude of [(18)F]-FLT uptake should not be considered a surrogate of proliferative index. These data rationalize the diversity of [(18)F]-FLT-PET correlative results previously reported and suggest future best-practices when [(18)F]-FLT-PET is employed in oncology.

Dataset Information

Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18F-FDG and 18F-FLT PET/CT imaging.

Publications

Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined <sup>18</sup>F-FDG and <sup>18</sup>F-FLT PET/CT imaging.

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