Dynamic 18F-FDopa PET Imaging for Newly Diagnosed Gliomas: Is a Semiquantitative Model Sufficient?

PurposeDynamic amino acid positron emission tomography (PET) has become essential in neuro-oncology, most notably for its prognostic value in the noninvasive prediction of isocitrate dehydrogenase (IDH) mutations in newly diagnosed gliomas. The 6-[18F]fluoro-l-DOPA (18F-FDOPA) kinetic model has an underlying complexity, while previous studies have predominantly used a semiquantitative dynamic analysis. Our study addresses whether a semiquantitative analysis can capture all the relevant information contained in time–activity curves for predicting the presence of IDH mutations compared to the more sophisticated graphical and compartmental models.MethodsThirty-seven tumour time–activity curves from 18F-FDOPA PET dynamic acquisitions of newly diagnosed gliomas (median age = 58.3 years, range = 20.3–79.9 years, 16 women, 16 IDH-wild type) were analyzed with a semiquantitative model based on classical parameters, with (SQ) or without (Ref SQ) a reference region, or on parameters of a fit function (SQ Fit), a graphical Logan model with input function (Logan) or reference region (Ref Logan), and a two-tissue compartmental model previously reported for 18F-FDOPA PET imaging of gliomas (2TCM). The overall predictive performance of each model was assessed with an area under the curve (AUC) comparison using multivariate analysis of all the parameters included in the model. Moreover, each extracted parameter was assessed in a univariate analysis by a receiver operating characteristic curve analysis.ResultsThe SQ model with an AUC of 0.733 for predicting IDH mutations showed comparable performance to the other models with AUCs of 0.752, 0.814, 0.693, 0.786, and 0.863, respectively corresponding to SQ Fit, Ref SQ, Logan, Ref Logan, and 2TCM (p ≥ 0.10 for the pairwise comparisons with other models). In the univariate analysis, the SQ time-to-peak parameter had the best diagnostic performance (75.7% accuracy) compared to all other individual parameters considered.ConclusionsThe SQ model circumvents the complexities of the 18F-FDOPA kinetic model and yields similar performance in predicting IDH mutations when compared to the other models, most notably the compartmental model. Our study provides supportive evidence for the routine clinical application of the SQ model for the dynamic analysis of 18F-FDOPA PET images in newly diagnosed gliomas.

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Dynamic 18F-FDopa PET Imaging for Newly-diagnosed Gliomas: Is a Semi-quantitative Model Sufficient?

10.21203/rs.3.rs-560933/v1 ◽

2021 ◽

Author(s):

Timothée ZARAGORI ◽

Matthieu Doyen ◽

Fabien Rech ◽

Marie Blonski ◽

Luc Taillandier ◽

...

Keyword(s):

Kinetic Model ◽

Dynamic Analysis ◽

Pet Imaging ◽

Compartmental Model ◽

Area Under The Curve ◽

Quantitative Model ◽

Newly Diagnosed ◽

Reference Region ◽

Time Activity ◽

Idh Mutations

Abstract Purpose: Even though the semi quantitative dynamic analysis of 18F-FDOPA PET effectively and non-invasively predicts isocitrate dehydrogenase (IDH) mutations in newly-diagnosed gliomas, the underlying kinetic model of 18F-FDOPA is complex. Our current study addresses whether a semi quantitative analysis indeed captures all the clinically relevant predictive features of the more sophisticated graphical and compartmental models.Methods: Thirty-seven tumour time-activity curves from 18F-FDOPA PET dynamic acquisitions of newly-diagnosed gliomas were analysed using a semi quantitative model with (Ref SQ) or without reference region (SQ), a graphical Logan model with input function (Logan) or reference region (Ref Logan), and a two-tissue compartmental model validated for 18F-FDOPA PET imaging in gliomas (2TCM). The overall predictive performance of each model for predicting IDH mutations was assessed, by an area under the curve (AUC) comparison of multivariate analyses of all parameters included in the model.Results: SQ model with an AUC of 0.733 showed comparable performances to other models with AUCs of 0.814, 0.693, 0.786, 0.863, respectively corresponding to Ref SQ, Logan, Ref Logan and 2 TCM (p≥0.11 for the pairwise comparisons with other models). SQ time-to-peak parameter had the best diagnostic performance relative to all individual parameters with an accuracy of 75.7%.Conclusions: The SQ model circumvents the complexities of the 18F-FDOPA kinetic model and yields similar performances compared to other models most notably the compartmental model for predicting IDH mutations. This validates the application of the SQ model for the dynamic analysis of 18F-FDOPA PET images in routine clinical practice for newly-diagnosed gliomas.

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Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173

BioMed Research International ◽

10.1155/2013/835859 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Nedim C. M. Gulaldi ◽

Jinsong Xia ◽

Tao Feng ◽

Kelvin Hong ◽

William B. Mathews ◽

...

Keyword(s):

Pet Imaging ◽

Compartmental Model ◽

Radioligand Binding ◽

Left Kidney ◽

Binding Parameters ◽

Retention Parameter ◽

Time Activity ◽

Kinetics Of

Purpose. The radioligand [11C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R). The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR).Procedures. Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney. To achieve IR, acute ischemia was created with a balloon inserted into the left renal artery and inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the balloon. Blood chemistries, urine specific gravity and PH values, and circulating hormones of the renin angiotensin system were measured and PET imaging was performed one week after IR. Cortical time-activity curves obtained from a 90 min [11C]KR31173 dynamic PET study were processed with a compartmental model that included two tissue compartments connected in parallel. Radioligand binding quantified by radioligand retention (80 min value to maximum value ratio) was compared to the binding parameters derived from the compartmental model. A binding ratio was calculated asDVR=DVS/DVNS, whereDVSandDVNSrepresented the distribution volumes of specific binding and nonspecific binding. Receptor binding was also determined by autoradiographyin vitro.Results. Correlations between rate constants and binding parameters derived by the convolution and deconvolution curve fittings were significant(r>0.9). Also significant was the correlation between the retention parameter derived from the tissue activity curve (Yret) and the retention parameter derived from the impulse response function (fret). Furthermore, significant correlations were found between these two retention parameters and DVR. Measurements with PET showed no significant changes in the radioligand binding parameters caused by IR, and thesein vivofindings were confirmed by autoradiography performedin vitro.Conclusions. Correlations between various binding parameters support the concept of the parallel connectivity compartmental model. If an arterial input function cannot be obtained, simple radioligand retention may be adequate for estimation ofin vivoradioligand binding.

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Impact of Lymphovascular Invasion on Prognosis in the Patients with Bladder Cancer—Comparison of Transurethral Resection and Radical Cystectomy

Diagnostics ◽

10.3390/diagnostics11020244 ◽

2021 ◽

Vol 11 (2) ◽

pp. 244

Author(s):

Kei Yoneda ◽

Naoto Kamiya ◽

Takanobu Utsumi ◽

Ken Wakai ◽

Ryo Oka ◽

...

Keyword(s):

Multivariate Analysis ◽

Radical Cystectomy ◽

Transurethral Resection ◽

Lymphovascular Invasion ◽

Medical Center ◽

Univariate Analysis ◽

The Other ◽

Significant Prognostic Factor ◽

Cancer Specific Survival ◽

Positive Results

(1) Background: This study aimed to evaluate the associations of lymphovascular invasion (LVI) at first transurethral resection of bladder (TURBT) and radical cystectomy (RC) with survival outcomes, and to evaluate the concordance between LVI at first TURBT and RC. (2) Methods: We analyzed 216 patients who underwent first TURBT and 64 patients who underwent RC at Toho University Sakura Medical Center. (3) Results: LVI was identified in 22.7% of patients who underwent first TURBT, and in 32.8% of patients who underwent RC. Univariate analysis identified ≥cT3, metastasis and LVI at first TURBT as factors significantly associated with overall survival (OS) and cancer-specific survival (CSS). Multivariate analysis identified metastasis (hazard ratio (HR) 6.560, p = 0.009) and LVI at first TURBT (HR 9.205, p = 0.003) as significant predictors of CSS. On the other hand, in patients who underwent RC, ≥pT3, presence of G3 and LVI was significantly associated with OS and CSS in univariate analysis. Multivariate analysis identified inclusion of G3 as a significant predictor of OS and CSS. The concordance rate between LVI at first TURBT and RC was 48.0%. Patients with positive results for LVI at first TURBT and RC displayed poorer prognosis than other patients (p < 0.05). (4) Conclusions: We found that the combination of LVI at first TURBT and RC was likely to provide a more significant prognostic factor.

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Gambaran Kesadaran dan Intensi Remaja Kurus Tentang Latihan Fisik

International Journal of Seocology ◽

10.26891/jik.v14i1.2020.59-67 ◽

2021 ◽

Vol 14 (1) ◽

pp. 59

Author(s):

Farah Diba ◽

Zahtamal Zahtamal ◽

Imelda Pardede

Keyword(s):

Physical Exercise ◽

Univariate Analysis ◽

Public Health Problem ◽

Sampling Technique ◽

Descriptive Study ◽

The Other ◽

Nutritional Knowledge ◽

Good Intention ◽

Quantitative Descriptive ◽

Inadequate Food Intake

Underweight is a public health problem and the incidence rate is still increasing worldwide, including in Indonesia. This condition is more common in adolescents due to inadequate food intake and lack of nutritional knowledge. The other factor that determines nutritional status is physical exercise. The purpose of this study was to describe the awarenesss and intentions of underweight adolescents about physical exercise. This research was a quantitative descriptive study. It was conducted at SMA Negeri 5 and 3 in Pekanbaru. Ninety two underweight subjects were obtained by purposive sampling technique. Data collected using questionnaire and then analyzed by univariate analysis. The results of this study found that 63% underweight adolescent were female and they were experiencing mild to severe underweight. Most subjects have moderate awareness (77.2%) and good intention (64.13%) about physical exercise. It can be concluded that underweight adolescents have moderate awareness and good intention about physical exercise, despite they are being underweight.

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A BGK MODEL FOR CHEMICAL PROCESSES: THE REACTION-DIFFUSION APPROXIMATION

Mathematical Models and Methods in Applied Sciences ◽

10.1142/s0218202594000042 ◽

1994 ◽

Vol 04 (01) ◽

pp. 35-47 ◽

Cited By ~ 4

Author(s):

RENATO SPIGLER ◽

DAMIÁN H. ZANETTE

Keyword(s):

Kinetic Model ◽

Diffusion Approximation ◽

Reaction Diffusion ◽

Chemical Processes ◽

Reaction Diffusion Equations ◽

The Other ◽

Diffusion Equations ◽

Bgk Model ◽

Chemical Substances ◽

Chemical Effects

A BGK-type kinetic model is derived for describing the interaction of chemical substances. The ensuing equation is then solved asymptotically on certain space-time scales on which an appreciable interplay between kinetic and chemical effects, or the prevailing of one on the other, can be observed. The description of the interaction at the macroscopic level consists of a hierarchy of reaction-diffusion equations satisfied by the densities. Comparison is made with similar results previously obtained from certain phenomenological models, and illustrative examples are given.

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A New Method and Automatic Generation for Dynamic Analysis of Complex Planar Mechanisms Based on the Ordered Single-Opened-Chains

23rd Biennial Mechanisms Conference: Machine Elements and Machine Dynamics ◽

10.1115/detc1994-0260 ◽

1994 ◽

Author(s):

Jian-Qing Zhang ◽

Ting-Li Yang

Keyword(s):

Dynamic Analysis ◽

Dynamic Equation ◽

Automatic Generation ◽

The Other ◽

New Method ◽

Complex Mechanism ◽

Planar Mechanisms ◽

Spatial Mechanisms ◽

General Dynamic

Abstract This work presents a new method for kinetostatic analysis and dynamic analysis of complex planar mechanisms, i.e. the ordered single-opened-chains method. This method makes use of the ordered single-opened chains (in short, SOC,) along with the properties of SOC, and the network constraints relationship between SOC,. By this method, any planar complex mechanism can be automatically decomposed into a series of the ordered single-opened chains and the optimal structural decomposition route (s) can be automatically selected for dynamic analysis, the paper present the dynamic equation which can be used to solve both the kinetostatic problem and the general dynamic problem. The main advantage of the proposed approach is the possibility to reduce the number of equations to be solved simultaneously to the minimum, and its high automation as well. The other advantage is the simplification of the determination of the coefficients in the equations, and thus it maybe result in a much less time-consuming algorthem. The proposed approach is illustrated with three examples. The presented method can be easily extended to the dynamic analysis of spatial mechanisms.

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PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

Molecules ◽

10.3390/molecules25102289 ◽

2020 ◽

Vol 25 (10) ◽

pp. 2289

Author(s):

Naresh Damuka ◽

Paul Czoty ◽

Ashley Davis ◽

Michael Nader ◽

Susan Nader ◽

...

Keyword(s):

Pet Imaging ◽

Neurological Disorders ◽

Healthy Male ◽

Time Activity ◽

Positron Emission ◽

Pet Ct ◽

Scan Data ◽

The Brain ◽

Human Primate

Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

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In vitro and In vivo Assessment of Suitable Reference Region and Kinetic Modelling for the mGluR1 Radioligand [11C]ITDM in Mice

Molecular Imaging and Biology ◽

10.1007/s11307-019-01435-1 ◽

2019 ◽

Vol 22 (4) ◽

pp. 854-863 ◽

Cited By ~ 4

Author(s):

Daniele Bertoglio ◽

Jeroen Verhaeghe ◽

Špela Korat ◽

Alan Miranda ◽

Leonie wyffels ◽

...

Keyword(s):

Mouse Brain ◽

Pet Imaging ◽

Metabotropic Glutamate Receptor ◽

Kinetic Modelling ◽

Input Function ◽

Dependent Manner ◽

Reference Region ◽

Suitable Reference

Abstract Purpose This study aimed at investigating binding specificity, suitability of reference region-based kinetic modelling, and pharmacokinetics of the metabotropic glutamate receptor 1 (mGluR1) radioligand [11C]ITDM in mice. Procedures We performed in vivo blocking as well as displacement of [11C]ITDM during positron emission tomography (PET) imaging using the specific mGluR1 antagonist YM-202074. Additionally, we assessed in vitro blocking of [3H]ITDM at two different doses of YM-202074. As an alternative to reference region models, we validated the use of a noninvasive image-derived input function (IDIF) compared to an arterial input function measured with an invasive arteriovenous (AV) shunt using a population-based curve for radiometabolite correction and characterized the pharmacokinetic modelling of [11C]ITDM in the mouse brain. Finally, we also assessed semi-quantitative approaches. Results In vivo blocking with YM-202074 resulted in a decreased [11C]ITDM binding, ranging from − 35.8 ± 8.0 % in pons to − 65.8 ± 3.0 % in thalamus. Displacement was also markedly observed in all tested regions. In addition, in vitro [3H]ITDM binding could be blocked in a dose-dependent manner. The volume of distribution (VT) based on the noninvasive IDIF (VT (IDIF)) showed excellent agreement with the VT values based on the metabolite-corrected plasma input function regardless of the metabolite correction (r2 > 0.943, p < 0.0001). Two-tissue compartmental model (2TCM) was found to be the preferred model and showed optimal agreement with Logan plot (r2 > 0.960, p < 0.0001). A minimum scan duration of 80 min was required for proper parameter estimation. SUV was not reliable (r2 = 0.379, p = 0.0011), unlike the SUV ratio to the SUV of the input function, which showed to be a valid approach. Conclusions No suitable reference region could be identified for [11C]ITDM as strongly supported by in vivo and in vitro evidence of specific binding in all brain regions. However, by applying appropriate kinetic models, [11C]ITDM PET imaging represents a promising tool to visualize mGluR1 in the mouse brain.

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Outcomes of GDPT (gemcitabine, cisplatin, prednisone, thalidomide) versus CHOP in newly diagnosed peripheral T-cell lymphoma patients

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920923829 ◽

2020 ◽

Vol 12 ◽

pp. 175883592092382 ◽

Cited By ~ 1

Author(s):

Yuanyuan Sun ◽

Ling Li ◽

Xin Li ◽

Lei Zhang ◽

Xinhua Wang ◽

...

Keyword(s):

Gene Expression ◽

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

The Other ◽

Newly Diagnosed ◽

Peripheral T Cell Lymphoma ◽

Angioimmunoblastic T Cell Lymphoma ◽

Significant Difference ◽

Gene Expression Levels

Aim: To compare the outcomes of GDPT [gemcitabine (G), cisplatin (D), prednisone (P), thalidomide (T)] versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL (peripheral T-cell lymphoma). Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT (77 cases) and CHOP (76 cases) groups. Patients in each group were further divided into four subgroups: PTCL, not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALCL), angioimmunoblastic T cell lymphoma (AITL), and other types subgroup, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3, and ERCC1, patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, progression-free survival (PFS), and overall survival (OS) were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The overall response rate (ORR) of the GDPT group was better than that of the CHOP group (66.3% versus 50.0%, p = 0.042), as was the complete remission (CR) rate (42.9% versus 27.6%, p = 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% versus 53.0% for PFS, p = 0.035; 66.8% versus 53.6% for OS, p = 0.039). In the GDPT group, the difference in CR between the four subgroups was statistically significant ( p = 0.046). In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant ( p < 0.001 and p = 0.005, respectively). There were also statistically significant differences in CR between patients treated with CHOP and GDPT in the PTCL-NOS subgroup, AITL subgroup, and the other types subgroup ( p = 0.015; p = 0.003; p = 0.005, respectively). The data also showed a significant difference in OS among the four subgroups within the GDPT group ( p = 0.001). The OS of AITL was shorter than that of the other three subgroups. Four subgroups of CHOP showed a significant difference in PFS ( p = 0.019). There was no statistical association between responses and the gene expression levels of RRM1, ERCC1, TUBB3, and TOP2A. Conclusion: The GDPT group had better response rates and prolonged patient PFS and OS. As a promising new regimen, GDPT is expected to become the first-line therapy for PTCL. New agents should be applied to patients who do not achieve good responses with previous treatment, such as those diagnosed with angioimmunoblastic T cell lymphoma. Trial registration: This open randomized prospective clinical trial was registered at ClinicalTrials.gov (NCT01664975).

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