Variety and complexity of fluorine-18-labelled fluoro-2-deoxy-D-glucose accumulations in the oral cavity of patients with oral cancers.
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ABSTRACT:
SUBMITTER: Kito S
PROVIDER: S-EPMC3699977 | biostudies-other | 2013
REPOSITORIES: biostudies-other
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Project description:BackgroundSkeletal muscle glucose utilization is an important component of whole-body glucose consumption in normal humans. Fluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) is a non-invasive molecular imaging probe for evaluating tissue glucose utilization. It remains unclear whether or not 18 F-FDG uptake by skeletal muscle has utility as a biomarker for metabolic derangement. We investigated the utility of measurement of muscle 18 F-FDG positron emission tomography/computed tomography uptake as a surrogate marker for existing and incipient metabolic abnormalities.MethodsFluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) uptakes of insulin-sensitive organs (liver, pancreas, mesenteric visceral fat, psoas muscle, and abdominal subcutaneous fat) and their association with metabolic abnormalities were evaluated in an experimental group comprising 91 men and 66 women (mean age 49.9 ± 11.1 years). In this cross-sectional cohort, we assessed the predictive power of the optimal cut-off 18 F-FDG uptake [maximum standardized uptake value (SUVmax )]. We confirmed its feasibility and reliability for diagnosis of existing and incipient metabolic derangement in the validation group (longitudinal cohort comprising 91 men and 67 women; mean age 52.6 ± 7.9 years).ResultsFluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) uptake (SUVmax ) of psoas muscle was strongly correlated with clinical metabolic parameters in the experimental group. It was positively correlated with waist circumference, body mass index, fasting glucose, triglyceride, systolic and diastolic pressure, and negatively correlated with high-density lipoprotein cholesterol levels (for all, P < 0.05). SUVmax of the psoas muscle also showed the best area under the curve value (0.779) as a predictor of metabolic syndrome (MetS) in the experimental group. Using the optimal cut-off SUVmax of 1.34, the sensitivity, specificity, accuracy, positive, and negative predictive value for predicting existing MetS in the experimental group were 70.0%, 84.6%, 80.9%, 60.9%, and 89.2%, respectively. In the validation group, corresponding values were 47.6%, 92.3%, 86.1%, 50.0%, and 91.6%, respectively. Existing and incipient MetS were significantly higher in subjects with high 18 F-FDG uptake by the psoas muscle (SUVmax > 1.34). Subjects with higher psoas muscle SUVmax had a 3.3-fold increased risk of developing MetS (P = 0.017).ConclusionsFluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) uptake of psoas muscle is a promising surrogate marker for existing and incipient metabolic derangement.
| S-EPMC6711454 | biostudies-literature
Project description:ObjectivesThe evaluation of disease extent and post-therapy surveillance of head and neck cancer using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET is often complicated by physiological uptake in normal tissues of the head and neck region, especially after surgery or radiotherapy. However, irrespective of low positive predictive values, [18F]FDG PET remains the standard of care to stage the disease and monitor recurrences. Here, we report the preclinical use of a targeted poly (ADP-ribose) polymerase1 (PARP1) binding PET tracer, fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor ([18F]PARPi), as a potential alternative with greater specificity.MethodsUsing an orthotopic xenograft mouse model injected with either FaDu or Cal 27 (human squamous cell carcinoma cell lines) we performed PET/CT scans with the 2 tracers and compared the results. Gamma counts and autoradiography were also assessed and correlated with histology.ResultsThe average retained activity of [18F]PARPi across cell lines in tumor-bearing tongues was 0.9 ± 0.3%ID/g, 4.1 times higher than in control (0.2 ± 0.04%ID/g). Autoradiography and histology confirmed that the activity arose almost exclusively from the tumor areas, with a signal/normal tissue around a ratio of 42.9 ± 21.4. In vivo, [18F]PARPi-PET allowed delineation of tumor from healthy tissue (p < .005), whereas [18F]FDG failed to do so (p = .209).Conclusions and implications for patient careWe demonstrate that [18F]PARPi is more specific to tongue tumor tissue than [18F]FDG. [18F]PARPi PET allows for the straightforward delineation of oral cancer in mouse models, suggesting that clinical translation could result in improved imaging of head and neck cancer when compared to [18F]FDG.
| S-EPMC7253343 | biostudies-literature
Project description:ImportanceNeoadjuvant immunotherapy is a novel approach with the potential to improve outcomes for patients with oral cavity squamous cell cancer (OCSCC). Adverse events of varying severity are reported with immunotherapy, and a biomarker to predict response would be clinically useful to avoid toxic effects in those unlikely to benefit.ObjectiveTo correlate changes on fluoro-[18F]-deoxy-2-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans with primary tumor pathologic response and immunologic biomarkers in patients with OCSCC receiving neoadjuvant immunotherapy.Design, setting, and participantsThis was a retrospective analysis of serial FDG-PET/CT scans obtained prospectively as part of a phase 2 open-label randomized clinical trial investigating neoadjuvant immunotherapy in patients with untreated OCSCC between 2016 and 2019. Included were a total of 29 patients from a single academic medical center with untreated OCSCC (≥T2, or clinically node positive) randomized 1:1 to receive neoadjuvant therapy with single agent nivolumab or combination nivolumab and ipilimumab followed by surgery and standard of care adjuvant therapy.InterventionsThe interventions in this study were FDG-PET/CT scans before (T0) and after (T1) preoperative immunotherapy.Main outcomes and measuresData collected from FDG-PET/CT scans included maximum standardized uptake value (SUVmax) of primary OCSCC and cervical lymph nodes (LNs) at T0 and T1 and new LN uptake and uptake consistent with radiologic immune-related adverse events (irAEs) at T1. Primary OCSCC pathologic response reported as percentages of viable vs nonviable tumor. The number of CD8+ cells/mm2 was determined in the primary tumor biopsy specimen and at surgery.ResultsThere was no correlation between pathologic response and change in SUVmax in the primary OCSCC between T0 and T1. Out of 27 total participants, 13 had newly FDG-avid ipsilateral LNs at T1, most negative on pathology. A total of 9 had radiologic irAEs, most commonly sarcoid-like LN (7 of 27). No correlations were found between primary OCSCC SUVmax at T0 and CD8+ T-cell number in the primary tumor biopsy, and no correlations were found between primary OCSCC SUVmax at T1 and CD8+ T-cell number in the primary tumor at surgery.Conclusions and relevanceThere were no correlations between changes in FDG uptake after neoadjuvant immunotherapy and pathologic primary tumor response. Importantly, newly FDG-avid ipsilateral LNs following neoadjuvant immunotherapy were commonly observed but did not represent progressive disease or indicate pathologically disease positive nodes in most cases. These findings argue against altering surgical plans in this setting and suggest that the role of FDG-PET/CT may be limited as an early imaging biomarker for predicting pathologic response to preoperative immunotherapy for OCSCC.Trial registrationClinicalTrials.gov Identifier: NCT02919683.
| S-EPMC8778607 | biostudies-literature
Project description:PURPOSE:Taking full advantage of positron emission tomography (PET) technology, fluorine-18-labelled radiotracers targeting norepinephrine transporter (NET) have potential applications in the diagnosis and assessment of cardiac sympathetic nerve conditions as well as the delineation of neuroendocrine tumours. However, to date, none have been used clinically. Drawbacks of currently reported radiotracers include suboptimal kinetics and challenging radiolabelling procedures. PROCEDURES:We developed a novel fluorine-18-labelled radiotracer targeting NET, AF78, with efficient one-step radiolabelling based on the phenethylguanidine structure. Radiosynthesis of AF78 was undertaken, followed by validation in cell uptake studies, autoradiography, and in vivo imaging in rats. RESULTS:[18F]AF78 was successfully synthesized with 27.9?±?3.1 % radiochemical yield, >?97 % radiochemical purity and >?53.8 GBq/mmol molar activity. Cell uptake studies demonstrated essentially identical affinity for NET as norepinephrine and meta-iodobenzylgaunidine. Both ex vivo autoradiography and in vivo imaging in rats showed homogeneous and specific cardiac uptake. CONCLUSIONS:The new PET radiotracer [18F]AF78 demonstrated high affinity for NET and favourable biodistribution in rats. A structure-activity relationship between radiotracer structures and affinity for NET was revealed, which may serve as the basis for the further design of NET targeting radiotracers with favourable features.
| S-EPMC7250802 | biostudies-literature
Project description:Brain positron emission tomography (PET) imaging with radiolabelled proteins is an emerging concept that potentially enables visualization of unique molecular targets in the brain. However, the pharmacokinetics and protein radiolabelling methods remain challenging. Here, we report the performance of an engineered, blood-brain barrier (BBB)-permeable affibody molecule that exhibits rapid clearance from the brain, which was radiolabelled using a unique fluorine-18 labelling method, a cell-free protein radiosynthesis (CFPRS) system. AS69, a small (14 kDa) dimeric affibody molecule that binds to the monomeric and oligomeric states of α-synuclein, was newly designed for brain delivery with an apolipoprotein E (ApoE)-derived brain shuttle peptide as AS69-ApoE (22 kDa). The radiolabelled products 18F-AS69 and 18F-AS69-ApoE were successfully synthesised using the CFPRS system. Notably, 18F-AS69-ApoE showed higher BBB permeability than 18F-AS69 in an ex vivo study at 10 and 30 min post injection and was partially cleared from the brain at 120 min post injection. These results suggest that small, a brain shuttle peptide-fused fluorine-18 labelled protein binders can potentially be utilised for brain molecular imaging.
| S-EPMC7844286 | biostudies-literature
Project description:The role of human papillomavirus type 16 (HPV16) in oral potentially malignant disorders (OPMD) and oral cavity carcinoma (OC) is still under debate. We investigated HPV16 prevalence in unstimulated saliva, oral rinse samples, oral swabs and tumour biopsies collected from OPMD (n = 83) and OC (n = 106) patients. HPV16 genotype, viral load, physical status (episomal vs. integrated) and tumour p16INK4a expression were determined. Oral HPV16 prevalence was higher in OC than in OPMD, but this difference was not statistically significant (7.5% (8/106) versus 3.6% (3/83), odds ratio (OR): 2.18, 95% confidence interval (CI): 0.56, 8.48, p = 0.26). There was a significant association (p < 0.05) between oral HPV16 infection and heavy tobacco consumption. Real-time PCR results indicated that no integration events occurred in either OPMD or OC cases based on the HPV16 E2/E6 ratio. HPV16 positive OPMD and OC patients had similar HPV16 E2 and E6 viral loads. The inter-rater agreement between tumour p16INK4a expression and oral HPV16 infection was considered as fair (k = 0.361) for OC. Our data suggest that the involvement of HPV16 in oral carcinogenesis is limited.
| S-EPMC7072384 | biostudies-literature
Project description:We compared [(18)F]fluoro-2-deoxy-2-d-glucose (FDG) versus 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) for the purpose of identifying active pelvic bone marrow (BM), quantifying its locational variation, and determining which technique is likely to be better for BM-sparing radiation planning.We sampled 41 patients, of which 25 underwent FDG-PET/CT only, 7 underwent FLT-PET/CT only, and 9 underwent both. Active BM subvolumes were defined as subsets of the pelvic BM with the highest standardized uptake values comprising 40%, 50%, and 60% of the total pelvic BM volume. We used the Dice similarity coefficient to quantify the percent overlap of active BM volumes of equal size. Differences in the spatial distribution of active BM were assessed using a region-growing algorithm.For patients with both modalities, the mean Dice coefficients for the 40%, 50%, and 60% subvolumes were 0.683, 0.732, and 0.781 respectively. Comparing individual active BM subvolumes to the mean subvolume, Dice coefficients varied from 0.598-0.889 for FDG and 0.739-0.912 for FLT. Region growing analysis showed FLT-PET defined more highly clustered active BM subvolumes.Within the limitations of a small sample size, we found significant agreement between FDG-PET and FLT-PET; however, FLT-PET had significantly less individual variation and is likely to be superior to FDG-PET for BM-sparing radiotherapy.
| S-EPMC4764473 | biostudies-literature
Project description:The purpose of this study was to report the clinical outcomes and related prognostic factors of patients who underwent radiotherapy (RT) for the treatment of recurrent, never-irradiated oral cavity cancer (recurrent OCC).The records of consecutive patients with nonmetastatic recurrent OCC who presented to and were treated with RT at our institution between 1989 and 2011 were reviewed. The Kaplan-Meier method was used to calculate overall survival (OS). The cumulative incidences of disease-specific death, local failure, regional failure, and distant metastasis were calculated with death as a competing risk.One hundred twenty-three patients were identified. Median follow-up for living patients was 54 months and 16 months for all patients. Ninety-one patients had salvage surgery followed by adjuvant RT. Definitive RT was utilized in the remaining 32 patients. The 5-year OS was 40%. The 5-year cumulative incidence of disease-specific death, local failure, regional failure, and distant metastasis was 55%, 34%, 22%, and 20%, respectively. Recurrent T classification and lack of salvage surgery were independently associated with worse disease-specific death and decreased OS, respectively. Subset analysis of patients who underwent salvage surgery demonstrated that age, recurrent T classification, and perineural invasion (PNI) were independently associated with decreased OS; recurrent T classification and thicker tumors were independently associated with worse disease-specific death; and positive/close margins and primary T classification were independently associated with increased local failure.In this group of patients with recurrent OCC, clinical outcomes were similar or improved when compared with other recurrent OCC-specific reports. In the salvage surgery subset, tumor thickness and PNI are recurrent pathologic features associated with outcomes that were only previously demonstrated in studies of primary disease. Because of the relatively worse outcomes in patients receiving definitive or adjuvant RT for recurrent OCC, we advocate for the appropriate use of postoperative RT in the initial management of oral cavity cancers.
| S-EPMC4973396 | biostudies-literature
Project description:BACKGROUND:Targeted therapy of HER2 positive breast cancer has led to clinical success in some cases with primary and secondary resistance being major obstacles. Due to the substantial involvement of mTOR kinase in cell growth and proliferation pathways it is now targeted in combination treatments to counteract HER2 targeted therapy resistance. However, the selection of receptive patient populations for a specific drug combination is crucial. This work aims to develop a molecular probe capable of identifying patients with tumour populations which are receptive to RAD001 combination therapy. Based on the structure of a mTOR inhibitor specific for mTORC1, we designed, synthesised and characterised a novel benzofuran based molecular probe which suits late stage fluorination via Click chemistry. RESULTS:Synthesis of the alkyne precursor 5 proceeded in 27.5% yield over 7 linear steps. Click derivatisation gave the non-radioactive standard in 25% yield. Radiosynthesis of [18F]1-((1-(2-Fluoroethyl)-1H-1,2,3-triazol-4-yl) methyl)-4-((5-methoxy-2-phenylbenzofuran-4-yl) methyl) piperazine ([18F]mBPET-1) proceeded over two steps which were automated on an iPhase FlexLab synthesis module. In the first step, 2-[18F]fluoroethylazide ([18F]6) was produced, purified by automated distillation in 60% non-decay-corrected yield and subjected to Click conditions with 5. Semi-preparative RP-HPLC purification and reformulation gave [18F]mBPET-1 in 40%?±?5% (n?=?6) overall RCY with a process time of 90?min. Radiochemical purity was ?99% at end of synthesis (EOS) and???98% after 4?h at room temperature. Molar activities ranged from typically 24.8?GBq/?mol (EOS) to a maximum of 78.6?GBq/?mol (EOS). Lipophilicity of [18F]mBPET-1 was determined at pH?7.4 (logD7.4?=?0.89). [18F]mBPET-1 showed high metabolic stability when incubated with mouse S9 liver fractions which resulted in a 0.8% drop in radiochemical purity after 3?h. Cell uptake assays showed 1.3-1.9-fold increased uptake of the [18F]mBPET-1 in RAD001 sensitive compared to insensitive cells across a panel of 4 breast cancer cell lines. CONCLUSION:Molecular targeting of mTOR with [18F]mBPET-1 distinguishes mTOR inhibitor sensitive and insensitive cell lines. Future studies will explore the ability of [18F]mBPET-1 to predict response to mTOR inhibitor treatment in in vivo models.
| S-EPMC6977806 | biostudies-literature
Project description:Fatty acid amide hydrolase (FAAH), the enzyme responsible for terminating signaling by the endocannabinoid anandamide, plays an important role in the endocannabinoid system, and FAAH inhibitors are attractive drugs for pain, addiction, and neurological disorders. The synthesis, radiosynthesis, and evaluation, in vitro and ex vivo in rat, of an (18)F-radiotracer designed to image FAAH using positron emission tomography (PET) is described. Fluorine-18 labelled 3-(4,5-dihydrooxazol-2-yl)phenyl (5-fluoropentyl)carbamate, [(18)F]5, was synthesized at high specific activity in a one-pot three step reaction using a commercial module with a radiochemical yield of 17-22% (from [(18)F]fluoride). In vitro assay using rat brain homogenates showed that 5 inhibited FAAH in a time-dependent manner, with an IC50 value of 0.82nM after a preincubation of 60min. Ex vivo biodistribution studies and ex vivo autoradiography in rat brain demonstrated that [(18)F]5 had high brain penetration with standard uptake values of up to 4.6 and had a regional distribution which correlated with reported regional FAAH enzyme activity. Specificity of binding to FAAH with [(18)F]5 was high (>90%) as demonstrated by pharmacological challenges with potent and selective FAAH inhibitors and was irreversible as demonstrated by radioactivity measurements on homogenized brain tissue extracts. We infer from these results that [(18)F]5 is a highly promising candidate radiotracer with which to image FAAH in human subjects using PET and clinical studies are proceeding.
| S-EPMC3683374 | biostudies-literature