Dataset Information

Feasibility of ¹⁸F-Fluorocholine PET for Evaluating Skeletal Muscle Atrophy in a Starved Rat Model.

ABSTRACT: Imaging techniques for diagnosing muscle atrophy and sarcopenia remain insufficient, although various advanced diagnostic methods have been established. We explored the feasibility of ¹⁸F-fluorocholine (¹⁸F-FCH) positron emission tomography/computed tomography (PET/CT) for evaluating skeletal muscle atrophy, as an imaging technique that tracks choline level changes in muscles. Cell uptake in L6 cells by ¹⁸F-FCH was performed in a complete medium containing serum (untreated group, UN) and a serum-free medium (starved group, ST). Small-animal-dedicated PET/CT imaging with ¹⁸F-FCH was examined in in-vivo models with rats that were starved for 2 days to cause muscle atrophy. After the hind limbs were dissected, starvation-induced in-vivo models were anatomically confirmed by reverse-transcription polymerase chain reaction to evaluate the expression levels of the atrophy markers muscle RING-finger protein-1 (MuRF-1) and atrogin-1. ¹⁸F-FCH uptake was lower in the starvation-induced cells than in the untreated group, and in-vivo PET uptake also revealed a similar tendency (the average standardized uptake value (SUV_mean) = 0.26 ± 0.06 versus 0.37 ± 0.07, respectively). Furthermore, the expression levels of MuRF-1 and atrogin-1 mRNA were significantly increased in the starvation-induced muscle atrophy of rats compared to the untreated group. ¹⁸F-FCH PET/CT may be a promising tool for diagnosing skeletal muscle atrophy.

SUBMITTER: Park SM

PROVIDER: S-EPMC9141294 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Feasibility of 18F-Fluorocholine PET for Evaluating Skeletal Muscle Atrophy in a Starved Rat Model.

Park Sun Mi SM Kim Jisu J Baek Suji S Jeon Joo-Yeong JY Lee Sang Ju SJ Kang Seo Young SY Yoo Min Young MY Yoon Hai-Jeon HJ Kwon Seung Hae SH Lim Kiwon K Oh Seung Jun SJ Kim Bom Sahn BS Lee Kang Pa KP Moon Byung Seok BS

Diagnostics (Basel, Switzerland) 20220520 5

Imaging techniques for diagnosing muscle atrophy and sarcopenia remain insufficient, although various advanced diagnostic methods have been established. We explored the feasibility of 18F-fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) for evaluating skeletal muscle atrophy, as an imaging technique that tracks choline level changes in muscles. Cell uptake in L6 cells by 18F-FCH was performed in a complete medium containing serum ...[more]

PMID: 35626428

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Project description:Purpose[18F]fluorocholine PET/CT can detect hepatocellular carcinoma (HCC) based on imaging the initial steps of phosphatidylcholine synthesis. To relate the diagnostic performance of [18F]fluorocholine positron emission tomography (PET)/x-ray computed tomography (CT) to the phospholipid composition of liver tumors, radiopathologic correspondence was performed in patients with early-stage liver cancer who had undergone [18F]fluorocholine PET/CT before tumor resection.ProceduresTumor and adjacent liver were profiled by liquid chromatography mass spectrometry, quantifying phosphatidylcholine species by mass-to-charge ratio. For clinical-radiopathologic correlation, HCC profiles were reduced to two orthogonal principal component factors (PCF1 and PCF2) accounting for 80 % of total profile variation.ResultsTissues from 31 HCC patients and 4 intrahepatic cholangiocarcinoma (ICC) patients were analyzed, revealing significantly higher levels of phosphocholine, CDP-choline, and highly saturated phosphatidylcholine species in HCC tumors relative to adjacent liver and ICC tumors. Significant loading values for PCF1 corresponded to phosphatidylcholines containing poly-unsaturated fatty acids while PCF2 corresponded only to highly saturated phosphatidylcholines. Only PCF2 correlated significantly with HCC tumor-to-liver [18F]fluorocholine uptake ratio (ρ = 0.59, p < 0.0005). Sensitivity for all tumors based on an abnormal [18F]fluorocholine uptake ratio was 93 % while sensitivity for HCC based on increased tumor [18F]fluorocholine uptake was 84 %, with lower levels of highly saturated phosphatidylcholines in tumors showing low [18F]fluorocholine uptake.ConclusionMost HCC tumors contain high levels of saturated phosphatidylcholines, supporting their dependence on de novo fatty acid metabolism for phospholipid membrane synthesis. While [18F]fluorocholine PET/CT can serve to identify these lipogenic tumors, its imperfect diagnostic sensitivity implies metabolic heterogeneity across HCC and a weaker lipogenic phenotype in some tumors.

Project description:BackgroundThe optimal condition for the clinical application of 18F-fluorocholine positron emission tomography-computed tomography (FCH-PET/CT) to detect recurrence sites in prostate-specific antigen (PSA) failure remains unclear due to the heterogeneity of prostate cancer failure. We aimed to evaluate the detection rate of FCH-PET/CT in prostate cancer patients with PSA failure and to determine the optimal PSA level for performing FCH-PET/CT.MethodsFCH-PET/CT was conducted in 89 patients diagnosed with PSA failure after radical treatment (radical prostatectomy in 75 and definitive radiotherapy in 14) between November 2018 and May 2021. Detection rates were examined via receiver operating characteristic (ROC) analysis, and multivariable logistic regression was performed to identify factors affecting positive FCH-PET/CT findings. We also conducted subgroup analyses according to the PSA failure patterns after the radical treatment (persistently high PSA [N = 48] and biochemical recurrence [BCR] [N = 41]).ResultsFCH-PET/CT demonstrated a 59.6% overall detection rate, and the optimal PSA threshold for detecting positive findings was ≥ 1.00 ng/mL at the time of imaging. On multivariable analysis, PSA > 1.00 ng/mL (P < 0.001) was a significant predictor of positive FCH-PET/CT findings, especially regarding distant bone metastases (P < 0.001) and recurrence outside the pelvis (P < 0.001). In a subgroup analysis of patients with BCR after initial radical treatment, the area under the ROC curve (AUC) was 0.82, and PSA ≥ 1.75 ng/mL was the optimal value for identifying positive FCH-PET/CT findings. This PSA value was also associated with significantly higher detection rates of distant bone metastases and outside-pelvis metastasis (P < 0.001, both).ConclusionFCH-PET/CT is a clinically useful tool for detecting tumor recurrence sites in prostate cancer patients with PSA failure if PSA has exceeded a certain value at the time of imaging. Particularly, higher AUC values were observed when FCH-PET/CT was performed in patients with BCR after initial treatment.

Project description:PurposeRadiographic changes of brain metastases after stereotactic radiosurgery (SRS) can signify tumor recurrence and/or radiation necrosis (RN); however, standard imaging modalities cannot easily distinguish between these two entities. We investigated whether 18F-Fluorocholine uptake in surgical samples of the resected lesions correlates with pathologic evidence of recurrent tumor and PET imaging.MethodsAbout 14 patients previously treated with SRS that developed radiographic changes were included. All patients underwent a preoperative 40-min dynamic PET/CT concurrent with 392 ± 11 MBq bolus injection of 18F-Fluorocholine. 18F-Fluorocholine pharmacokinetics were evaluated by standardized uptake value (SUV), graphical analysis (Patlak plot; KiP) and an irreversible two-compartment model (K1, k2, k3, and Ki). 12 out of 14 patients were administered an additional 72 ± 14 MBq injection of 18F-Fluorocholine 95 ± 26 minutes prior to surgical resection. About 113 resected samples from 12 patients were blindly reviewed by a neuropathologist to assess the viable tumor and necrotic content, microvascular proliferation, reactive gliosis, and mono- and polymorphonuclear inflammatory infiltrates. Correlation between these metrics 18F-Fluorocholine SUV was investigated with a linear mixed model. Comparison of survival distributions of two groups of patients (population median split of PET SUVmax) was performed with the log-rank test.ResultsExactly 10 out of 12 patients for which surgical samples were acquired exhibited pathologic recurrence. Strong correlation was observed between SUVmax as measured from a surgically removed sample with highest uptake and by PET (Pearson's r = 0.66). Patients with 18F-Fluorocholine PET SUVmax > 6 experienced poor survival. Surgical samples with viable tumor had higher 18F-fluorocholine uptake (SUV) than those without tumor (4.5 ± 3.7 and 2.6 ± 3.0; p = 0.01). 18F-fluorocholine count data from surgical samples is driven not only by the percentage viable tumor but also by the degree of inflammation and reactive gliosis (p ≤ 0.02; multivariate regression).Conclusions18F-Fluorocholine accumulation is increased in viable tumor; however, inflammation and gliosis may also lead to elevated uptake. Higher 18F-Fluorocholine PET uptake portends worse prognosis. Kinetic analysis of dynamic 18F-Fluorocholine PET imaging supports the adequacy of the simpler static SUV metric.

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Dataset Information

Feasibility of ¹⁸F-Fluorocholine PET for Evaluating Skeletal Muscle Atrophy in a Starved Rat Model.

Publications

Feasibility of <sup>18</sup>F-Fluorocholine PET for Evaluating Skeletal Muscle Atrophy in a Starved Rat Model.

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