Effective Detection and Monitoring of Glioma Using [18F]FPIA PET Imaging.
Ontology highlight
ABSTRACT: Background
Reprogrammed cellular metabolism is a cancer hallmark. In addition to increased glycolysis, the oxidation of acetate in the citric acid cycle is another common metabolic phenotype. We have recently developed a novel fluorine-18-labelled trimethylacetate-based radiotracer, [18F]fluoro-pivalic acid ([18F]FPIA), for imaging the transcellular flux of short-chain fatty acids, and investigated whether this radiotracer can be used for the detection of glioma growth.Methods
We evaluated the potential of [18F]FPIA PET to monitor tumor growth in orthotopic patient-derived (HSJD-GBM-001) and cell line-derived (U87, LN229) glioma xenografts, and also included [18F]FDG PET for comparison. We assessed proliferation (Ki-67) and the expression of lipid metabolism and transport proteins (CPT1, SLC22A2, SLC22A5, SLC25A20) by immunohistochemistry, along with etomoxir treatment to provide insights into [18F]FPIA uptake.Results
Longitudinal PET imaging showed gradual increase in [18F]FPIA uptake in orthotopic glioma models with disease progression (p < 0.0001), and high tumor-to-brain contrast compared to [18F]FDG (p < 0.0001). [18F]FPIA uptake correlated positively with Ki-67 (p < 0.01), SLC22A5 (p < 0.001) and SLC25A20 (p = 0.001), and negatively with CPT1 (p < 0.01) and SLC22A2 (p < 0.01). Etomoxir reduced [18F]FPIA uptake, which correlated with decreased Ki-67 (p < 0.05).Conclusions
Our findings support the use of [18F]FPIA PET for the detection and longitudinal monitoring of glioma, showing a positive correlation with tumor proliferation, and suggest transcellular flux-mediated radiotracer uptake.
SUBMITTER: Vassileva V
PROVIDER: S-EPMC8301305 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Poly(ADP-ribose) polymerase (PARP) inhibitors are increasingly being studied as cancer drugs, as single agents, or as a part of combination therapies. Imaging of PARP using a radiolabeled inhibitor has been proposed for patient selection, outcome prediction, dose optimization, genotoxic therapy evaluation, and target engagement imaging of novel PARP-targeting agents. Methods: Here, via the copper-mediated 18F-radiofluorination of aryl boronic esters, we accessed, for the first time (to our knowledge), the 18F-radiolabeled isotopolog of the Food and Drug Administration-approved PARP inhibitor olaparib. The use of the 18F-labeled equivalent of olaparib allows direct prediction of the distribution of olaparib, given its exact structural likeness to the native, nonradiolabeled drug. Results: 18F-olaparib was taken up selectively in vitro in PARP-1-expressing cells. Irradiation increased PARP-1 expression and 18F-olaparib uptake in a radiation-dose-dependent fashion. PET imaging in mice showed specific uptake of 18F-olaparib in tumors expressing PARP-1 (3.2% ± 0.36% of the injected dose per gram of tissue in PSN-1 xenografts), correlating linearly with PARP-1 expression. Two hours after irradiation of the tumor (10 Gy), uptake of 18F-olaparib increased by 70% (P = 0.025). Conclusion: Taken together, we show that 18F-olaparib has great potential for noninvasive tumor imaging and monitoring of radiation damage.
| S-EPMC6448459 | biostudies-literature
Project description:Cancer immunotherapy urgently calls for methods to monitor immune responses at the site of the cancer. Since activated T lymphocytes may serve as a hallmark for anticancer responses, we targeted these cells using the radiotracer N-(4-[18F]fluorobenzoyl)-interleukin-2 ([18F]FB-IL-2) for positron emission tomography (PET) imaging. Thus, we noninvasively monitored the effects of local tumor irradiation and/or immunization on tumor-infiltrating and systemic activated lymphocytes in tumor-bearing mice. A 10- and 27-fold higher [18F]FB-IL-2 uptake was observed in tumors of mice receiving tumor irradiation alone or in combination with immunization, respectively. This increased uptake was extended to several non-target tissues. Administration of the CXCR4 antagonist AMD3100 reduced tracer uptake by 2.8-fold, indicating a CXCR4-dependent infiltration of activated T lymphocytes upon cancer treatment. In conclusion, [18F]FB-IL-2 PET can serve as a clinical biomarker to monitor treatment-induced infiltration of activated T lymphocytes and, on that basis, may guide cancer immunotherapies.
| S-EPMC5283633 | biostudies-literature
Project description:BackgroundA low amount and extent of Aβ deposition at early stages of Alzheimer's disease (AD) may limit the use of previously developed pathology-proven composite SUVR cutoffs. This study aims to characterize the population with earliest abnormal Aβ accumulation using 18F-florbetaben PET. Quantitative thresholds for the early (SUVRearly) and established (SUVRestab) Aβ deposition were developed, and the topography of early Aβ deposition was assessed. Subsequently, Aβ accumulation over time, progression from mild cognitive impairment (MCI) to AD dementia, and tau deposition were assessed in subjects with early and established Aβ deposition.MethodsThe study population consisted of 686 subjects (n = 287 (cognitively normal healthy controls), n = 166 (subjects with subjective cognitive decline (SCD)), n = 129 (subjects with MCI), and n = 101 (subjects with AD dementia)). Three categories in the Aβ-deposition continuum were defined based on the developed SUVR cutoffs: Aβ-negative subjects, subjects with early Aβ deposition ("gray zone"), and subjects with established Aβ pathology.ResultsSUVR using the whole cerebellum as the reference region and centiloid (CL) cutoffs for early and established amyloid pathology were 1.10 (13.5 CL) and 1.24 (35.7 CL), respectively. Cingulate cortices and precuneus, frontal, and inferior lateral temporal cortices were the regions showing the initial pathological tracer retention. Subjects in the "gray zone" or with established Aβ pathology accumulated more amyloid over time than Aβ-negative subjects. After a 4-year clinical follow-up, none of the Aβ-negative or the gray zone subjects progressed to AD dementia while 91% of the MCI subjects with established Aβ pathology progressed. Tau deposition was infrequent in those subjects without established Aβ pathology.ConclusionsThis study supports the utility of using two cutoffs for amyloid PET abnormality defining a "gray zone": a lower cutoff of 13.5 CL indicating emerging Aβ pathology and a higher cutoff of 35.7 CL where amyloid burden levels correspond to established neuropathology findings. These cutoffs define a subset of subjects characterized by pre-AD dementia levels of amyloid burden that precede other biomarkers such as tau deposition or clinical symptoms and accelerated amyloid accumulation. The determination of different amyloid loads, particularly low amyloid levels, is useful in determining who will eventually progress to dementia. Quantitation of amyloid provides a sensitive measure in these low-load cases and may help to identify a group of subjects most likely to benefit from intervention.Trial registrationData used in this manuscript belong to clinical trials registered in ClinicalTrials.gov ( NCT00928304 , NCT00750282 , NCT01138111 , NCT02854033 ) and EudraCT (2014-000798-38).
| S-EPMC8005243 | biostudies-literature
Project description:BackgroundInflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover.ObjectivesThis study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation.MethodsWe confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis.ResultsTarget SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients.ConclusionsWe validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188).
| S-EPMC5381358 | biostudies-literature
Project description:PurposeThis study aimed to determine the impact of carbidopa premedication on static, dynamic and radiomics parameters of 18F-FDOPA PET in brain tumors.MethodsThe study included 54 patients, 18 of whom received carbidopa, who underwent 18F-FDOPA PET for newly diagnosed gliomas. SUV-derived, 105 radiomics features and TTP dynamic parameters were extracted from volumes of interest in healthy brains and tumors. Simulation of the effects of carbidopa on time-activity curves were generated.ResultsAll static and TTP dynamic parameters were significantly higher in healthy brain regions of premedicated patients (ΔSUVmean = +53%, ΔTTP = +48%, p < 0.001). Furthermore, carbidopa impacted 81% of radiomics features, of which 92% correlated with SUVmean (absolute correlation coefficient ≥ 0.4). In tumors, premedication with carbidopa was an independent predictor of SUVmean (ΔSUVmean = +52%, p < 0.001) and TTP (ΔTTP = +24%, p = 0.025). All parameters were no longer significantly modified by carbidopa premedication when using ratios to healthy brain. Simulated data confirmed that carbidopa leads to higher tumor TTP values, corrected by the ratios.ConclusionIn 18F-FDOPA PET, carbidopa induces similarly higher SUV and TTP dynamic parameters and similarly impacts SUV-dependent radiomics in healthy brain and tumor regions, which is compensated for by correcting for the tumor-to-healthy-brain ratio. This is a significant advantage for multicentric study harmonization.
| S-EPMC8582429 | biostudies-literature
Project description:PurposeThe aim of this study was to examine whether the translocator protein 18-kDa (TSPO) PET ligand [18F]FEPPA has the sensitivity for detecting changes in CD68-positive microglial/macrophage activation in hemiparkinsonian rhesus macaques treated with allogeneic grafts of induced pluripotent stem cell-derived midbrain dopaminergic neurons (iPSC-mDA).MethodsIn vivo positron emission tomography (PET) imaging with [18F]FEPPA was used in conjunction with postmortem CD68 immunostaining to evaluate neuroinflammation in the brains of hemiparkinsonian rhesus macaques (n = 6) that received allogeneic iPSC-mDA grafts in the putamen ipsilateral to MPTP administration.ResultsBased on assessment of radiotracer uptake and confirmed by visual inspection of the imaging data, nonhuman primates with allogeneic grafts showed increased [18F]FEPPA binding at the graft sites relative to the contralateral putamen. From PET asymmetry analysis of the images, the mean asymmetry index of the monkeys was AI = - 0.085 ± 0.018. Evaluation and scoring of CD68 immunoreactivity by an investigator blind to the treatment identified significantly more neuroinflammation in the grafted areas of the putamen compared to the contralateral putamen (p = 0.0004). [18F]FEPPA PET AI showed a positive correlation with CD68 immunoreactivity AI ratings in the monkeys (Spearman's ? = 0.94; p = 0.005).ConclusionThese findings reveal that [18F]FEPPA PET is an effective marker for detecting increased CD68-positive microglial/macrophage activation and demonstrates sufficient sensitivity to detect changes in neuroinflammation in vivo following allogeneic cell engraftment.
| S-EPMC7410886 | biostudies-literature
Project description:BackgroundCardiac PET has recently found novel applications in coronary atherosclerosis imaging using [18F]NaF as a radiotracer, highlighting vulnerable plaques. However, the resulting uptakes are relatively small, and cardiac motion and respiration-induced movement of the heart can impair the reconstructed images due to motion blurring and attenuation correction mismatches. This study aimed to apply an MR-based motion compensation framework to [18F]NaF data yielding high-resolution motion-compensated PET and MR images.MethodsFree-breathing 3-dimensional Dixon MR data were acquired, retrospectively binned into multiple respiratory and cardiac motion states, and split into fat and water fraction using a model-based reconstruction framework. From the dynamic MR reconstructions, both a non-rigid cardiorespiratory motion model and a motion-resolved attenuation map were generated and applied to the PET data to improve image quality. The approach was tested in 10 patients and focal tracer hotspots were evaluated concerning their target-to-background ratio, contrast-to-background ratio, and their diameter.ResultsMR-based motion models were successfully applied to compensate for physiological motion in both PET and MR. Target-to-background ratios of identified plaques improved by 7 ± 7%, contrast-to-background ratios by 26 ± 38%, and the plaque diameter decreased by -22 ± 18%. MR-based dynamic attenuation correction strongly reduced attenuation correction artefacts and was not affected by stent-related signal voids in the underlying MR reconstructions.ConclusionsThe MR-based motion correction framework presented here can improve the target-to-background, contrast-to-background, and width of focal tracer hotspots in the coronary system. The dynamic attenuation correction could effectively mitigate the risk of attenuation correction artefacts in the coronaries at the lung-soft tissue boundary. In combination, this could enable a more reproducible and reliable plaque localisation.
| S-EPMC8241750 | biostudies-literature
Project description:PET imaging of amino acid transport using O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) and proton MR spectroscopy (MRS) imaging of cell turnover measured by the ratio of choline to N-acetyl-aspartate (Cho/NAA) may provide additional information on tumor extent of cerebral gliomas compared with anatomic imaging; however, comparative studies are rare. Methods: In this prospective study, 41 patients (16 women, 25 men; mean age ± SD, 48 ± 14 y) with cerebral gliomas (World Health Organization [WHO] grade II: 10 [including 1 patient with 2 lesions], WHO III: 17, WHO IV: 13, without biopsy low-grade: 1, high-grade: 1) were investigated with a hybrid PET/MR scanner. Tumor extent, spatial overlap, and the distance between the corresponding centers of mass in 18F-FET PET and MRS imaging of Cho/NAA, determined by simultaneously acquired, 3-dimensional spatially resolved MRS imaging data, were compared. Results: The average tumor volumes for 18F-FET uptake and increased Cho/NAA were 19 ± 20 cm3 (mean ± SD) and 22 ± 24 cm3, respectively, with an overlap of 40% ± 25% and separation of the centers of mass by 9 ± 8 mm. None of the parameters showed a significant correlation with tumor grade. Conclusion:18F-FET uptake and increased Cho/NAA ratio are not always congruent and may represent different properties of glioma metabolism. The relationship to histologic tumor extent needs to be further analyzed.
| S-EPMC5932747 | biostudies-literature
Project description:PurposeThe aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection.MethodsTwenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI.Results18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5?±?2.3), while 11C-Methionine's tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0?±?2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p?<?0.0001). This was due to 18F-Fluciclovine's lower background in normal brain tissue (0.5?±?0.2 compared to 1.3?±?0.4 for 11C-Methionine). 18F-Fluciclovine uptake in both normal brain and tumors was well described by a simple one-compartment (three-parameter: Vb,k1,k2) model. Normal brain was found to approach transient equilibrium with a half-time that varied greatly, ranging from 1.5 to 8.3 h (mean 2.7?±?2.3 h), and achieving a consistent final distribution volume averaging 1.4?±?0.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57?±?51 min), with an average distribution volume of 3.2?±?1.1 ml/cc. A qualitative comparison showed that the rate of normal brain uptake of 11C-Methionine was much faster than that of 18F-Fluciclovine.ConclusionTumor uptake of 18F-Fluciclovine correlated well with the established brain tumor imaging agent 11C-Methionine but provided significantly higher image contrast. 18F-Fluciclovine may be particularly useful when the contrast MRI is non-diagnostic. Based on the data gathered, we were unable to determine whether Fluciclovine uptake was due solely to recurrent tumor or if inflammation or other processes also contributed.
| S-EPMC7188736 | biostudies-literature
Project description:PurposesChlorotoxin can specifically bind to matrix metalloproteinase 2 (MMP-2), which are overexpressed in the glioma. In this work, radiosynthesis of [18F]-fluoropropionyl-chlorotoxin ([18F]-FP-chlorotoxin) as a novel PET tracer was investigated, and biodistribution in vivo and PET imaging were performed in the C6 glioma model.Procedures[18F]-FP-chlorotoxin was prepared from the reaction of chlorotoxin with [18F]-NFB (4-nitrophenyl 2-[18F]-fluoropropionate), which was synthesized from multistep reactions. Biodistribution was determined in 20 normal Kunming mice. Small-animal PET imaging with [18F]-FP-chlorotoxin was performed on the same rats bearing orthotopic C6 glioma at different time points (60 min, 90 min, and 120 min) after injection and compared with 2-deoxy-2-[18F] fluoro-D-glucose ([18F]-FDG).Results[18F]-FP-Chlorotoxin was successfully synthesized in the radiochemical yield of 41% and the radiochemical purity of more than 98%. Among all the organs, the brain had the lowest and stable uptake of [18F]-FP-chlorotoxin, while the kidney showed the highest uptake. Compared with [18F]-FDG, a low uptake of [18F]-FP-chlorotoxin was detected in normal brain parenchyma and a high accumulation of [18F]-FP-chlorotoxin was found in the gliomas tissue. The glioma to normal brain uptake ratio of [18F]-FP-chlorotoxin was higher than that of [18F]-FDG. Furthermore, the uptake of [18F]-FP-chlorotoxin at 90 min after injection was better than that at 60 min after injection.ConclusionsCompared with [18F]-FDG, [18F]-FP-chlorotoxin has a low and stable uptake in normal brain parenchyma. [18F]-FP-Chlorotoxin seems to be a potential PET tracer with a good performance in diagnosis of the glioma.
| S-EPMC6317094 | biostudies-literature