Clinical characterization of hypoxia in pancreatic ductal adenocarcinoma (PDAC) by 18F-FAZA PET and pimonidazole.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4049-4049
Author(s):  
Cristiane Metran Nascente ◽  
Neesha C. Dhani ◽  
Douglass Vines ◽  
Ivan Yeung ◽  
Ur Metser ◽  
...  
Keyword(s):  
Functional Imaging ◽  
Tumor Biology ◽  
Automated Image Analysis ◽  
Ductal Adenocarcinoma ◽  
Significant Heterogeneity ◽  
Reference Tissue ◽  
Pet Tracer ◽  
Standardized Uptake Values ◽  
Positron Emission

4049 Background: We previously demonstrated correlation between hypoxia and aggressive tumor biology in orthotopic, patient-derived pancreatic xenografts (Chang et al. Cancer Res 2011). With the development of hypoxia-directed therapies, there is a need to understand the range and relevance of hypoxia in PDAC patients. We therefore launched two complementary clinical trials using 2-nitroimidazole-based hypoxia probes. Methods: PIMO-PANC involves pre-operative administration of pimonidazole to patients (pts) undergoing PDAC resection. Hypoxic percent (HP) of tumors is determined by semi-automated image analysis (on Aperio’s Genie) of multiple histological sections stained for pimonidazole by immunohistochemistry (IHC). FAZA-PANC uses the positron emission tomography (PET) tracer fluoroazomycin arabinoside (18F-FAZA) to evaluate hypoxia by functional imaging. 2 hours post-injection of (5.2 MBq/kg) 18F-FAZA, static scans are acquired followed by computed tomography for anatomic registration. Skeletal muscle is a non-hypoxic reference tissue to define standardized uptake values (SUV), tumor to muscle uptake ratios (T/M’s) and a threshold for hypoxia. Results: PIMO-PANC has enrolled 29 pts and FAZA-PANC 16. IHC analysis of the first 10 pt tumors demonstrates considerable intra- and inter-tumoral heterogeneity of hypoxia (HP: 1 to 26% across pt tumors); minimal hypoxia (< 5%) was observed in 3 pts. 18F-FAZA-PET in the first 11 pts demonstrates SUVmax from 1.02 to 1.83, median T/M's from 0.84 to 1.31. A threshold of 1.27 SUVmax defines HP of 0 to 60% with minimal hypoxia (<10%) in 5 pts. Conclusions: There is significant heterogeneity of hypoxia across the spectrum of clinical PDAC (local to metastatic disease) using the 2-nitroimidazole hypoxia probes pimonidazole and 18F-FAZA. Given the intra-tumoral heterogeneity of hypoxia by histopathology, functional imaging is the preferred method to assess hypoxia in PDAC patients. Importantly, both methods identified a group of PDAC tumors with low levels of hypoxia. This is relevant to the on-going development of hypoxia-targeting strategies. Accrual to PIMO-PANC is on-going and will address the prognostic relevance of hypoxia in PDAC. Clinical trial information: NCT01542177 and NCT01248637.

scholarly journals Multi-parametric PET/MRI With FDG and RGD for Enhanced Tumor Characterization of Patients With Cervical Cancer

2022 ◽  
Author(s):  
Sahar Ahangari ◽  
Flemming Littrup Andersen ◽  
Naja Liv Hansen ◽  
Trine Jakobi Nøttrup ◽  
Anne Kiil Berthelsen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cluster Analysis ◽  
Treatment Planning ◽  
Functional Imaging ◽  
Tumor Heterogeneity ◽  
Radiation Treatment ◽  
Fdg Uptake ◽  
Imaging Parameters ◽  
Standardized Uptake Values

Abstract Aim: The concept of personalized medicine has brought increased awareness to the importance of inter- and intra-tumor heterogeneity for cancer treatment. The aim of this study was to explore simultaneous multi-parametric PET/MRI prior to chemoradiotherapy for cervical cancer for characterization of tumors and tumor heterogeneity. Methods: Ten patients with histologically proven primary cervical cancer were examined with multi-parametric 68Ga-NODAGA-E[c(RGDyK)]2-PET/MRI for radiation treatment planning after diagnostic 18F-FDG-PET/CT. Standardized uptake values (SUV) of RGD and FDG, diffusion weighted MRI and the derived apparent diffusion coefficient (ADC), and pharmacokinetic maps obtained from dynamic contrast-enhanced MRI with the Tofts model (iAUC60, Ktrans, ve, and kep) were included in the analysis. The spatial relation between functional imaging parameters in tumors was examined by a correlation analysis and joint histograms at the voxel level. The ability of multi-parametric imaging to identify tumor tissue classes was explored using an unsupervised 3D Gaussian mixture model-based cluster analysis.Results: Functional MRI and PET of cervical cancers appeared heterogeneous both between patients and spatially within the tumors, and the relations between parameters varied strongly within the patient cohort. The strongest spatial correlation was observed between FDG uptake and ADC (median r=-0.7). There was moderate voxel-wise correlation between RGD and FDG uptake, and weak correlations between all other modalities. Distinct relations between the ADC and RGD uptake as well as the ADC and FDG uptake were apparent in joint histograms. A cluster analysis using the combination of ADC, FDG and RGD uptake suggested tissue classes which could potentially relate to tumor sub-volumes. Conclusion: A multi-parametric PET/MRI examination of patients with cervical cancer integrated with treatment planning and including estimation of angiogenesis and glucose metabolism as well as MRI diffusion and perfusion parameters is feasible. A combined analysis of functional imaging parameters indicates a potential of multi-parametric PET/MRI to contribute to a better characterization of tumor heterogeneity than the modalities alone. However, the study is based on small patient numbers and further studies are needed prior to the future design of individually adapted treatment approaches based on multi-parametric functional imaging.

scholarly journals A Proposed Dedicated Breast PET Lexicon: Standardization of Description and Reporting of Radiotracer Uptake in the Breast

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1267
Author(s):  
Kanae K. Miyake ◽  
Masako Kataoka ◽  
Takayoshi Ishimori ◽  
Yoshiaki Matsumoto ◽  
Masae Torii ◽  
...  
Keyword(s):  
Imaging Modality ◽  
Tumor Biology ◽  
Whole Body ◽  
Fdg Uptake ◽  
Dedicated Breast Pet ◽  
Radiotracer Uptake ◽  
Positron Emission ◽  
18F Fdg ◽  
Morphology Characterization

Dedicated breast positron emission tomography (dbPET) is a new diagnostic imaging modality recently used in clinical practice for the detection of breast cancer and the assessment of tumor biology. dbPET has higher spatial resolution than that of conventional whole body PET systems, allowing recognition of detailed morphological attributes of radiotracer accumulation within the breast. 18F-fluorodeoxyglucose (18F-FDG) accumulation in the breast may be due to benign or malignant entities, and recent studies suggest that morphology characterization of 18F-FDG uptake could aid in estimating the probability of malignancy. However, across the world, there are many descriptors of breast 18F-FDG uptake, limiting comparisons between studies. In this article, we propose a lexicon for breast radiotracer uptake to standardize description and reporting of image findings on dbPET, consisting of terms for image quality, radiotracer fibroglandular uptake, breast lesion uptake.

scholarly journals Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands

2017 ◽  
Vol 37 (9) ◽  
pp. 3243-3252 ◽  
Author(s):  
Melanie Ganz ◽  
Ling Feng ◽  
Hanne Demant Hansen ◽  
Vincent Beliveau ◽  
Claus Svarer ◽  
...  
Keyword(s):  
Regional Differences ◽  
Binding Potential ◽  
Reference Tissue ◽  
Tissue Modeling ◽  
Standardized Uptake Values ◽  
Positron Emission ◽  
Serotonin System ◽  
Signed Rank ◽  
The Impact ◽  
G Protein Coupled

In the quantification of positron emission tomography (PET) radiotracer binding, a commonly used method is reference tissue modeling (RTM). RTM necessitates a proper reference and a ubiquitous choice for G-protein coupled receptors is the cerebellum. We investigated regional differences in uptake within the grey matter of the cerebellar hemispheres (CH), the cerebellar white matter (CW), and the cerebellar vermis (CV) for five PET radioligands targeting the serotonin system. Furthermore, we evaluated the impact of choosing different reference regions when quantifying neocortical binding. The PET and MR images are part of the Cimbi database: 5-HT1AR ([11C]CUMI-101, n = 8), 5-HT1BR ([11C]AZ10419369, n = 36), 5-HT2AR ([11C]Cimbi-36, n = 29), 5-HT4R ([11C]SB207145, n = 59), and 5-HTT ([11C]DASB, n = 100). We employed SUIT and FreeSurfer to delineate CV, CW, and CH and quantified mean standardized uptake values (SUV) and nondisplaceable neocortical binding potential (BPND). Statistical difference was assessed with paired nonparametric two-sided Wilcoxon signed-rank tests and multiple comparison corrected via false discovery rate. We demonstrate significant radioligand specific regional differences in cerebellar uptake. These differences persist when using different cerebellar regions for RTM, but the influence on the neocortical BPND is small. Nevertheless, our data highlight the importance of validating each radioligand carefully for defining the optimal reference region.

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

Morphological and functional imaging allow better characterization of brown tumors in a patient with severe primary hyperparathyroidism

2014 ◽  
Author(s):  
Lavinia Vija ◽  
Diana Paun ◽  
Gilles Grimon ◽  
Frederique Archambaud ◽  
Philippe Chaumet-Riffaud
Keyword(s):  
Primary Hyperparathyroidism ◽  
Functional Imaging ◽  
Brown Tumors

Comparison of 18F-FDG and 67Ga-citrate in sarcoidosis imaging

2008 ◽  
Vol 47 (01) ◽  
pp. 18-23 ◽  
Author(s):  
M. Wehrschuetz ◽  
B. Bisail ◽  
M. Woltsche ◽  
T. Schwarz ◽  
H. Lanz ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Complete Agreement ◽  
Pet Tracer ◽  
Positron Emission ◽  
Significant Difference ◽  
Kappa Value ◽  
18F Fdg ◽  
Primary Assessment ◽  
67Ga Citrate

SummaryAim: 67Ga citrate has been used long and successfully to diagnose and stage sarcoidosis. 18F-fluorodeoxyglucose (18F-FDG) has been suggested as a positron emission tomography (PET) tracer for sarcoidosis imaging. This study aimed to analyze possible advantages of 18F-FDG-PET over 67Ga citrate scintigraphy during the primary assessment of patients with sarcoidosis. Patients and methods: Twentyfour patients (11 men, 13 women, aged 52 years ±12.4) with histologically proven sarcoidosis were investigated with 18F-FDG and 67Ga citrate. Equipment included a fullring PET scanner (ECAT EXACT HR+, Siemens/CTI, Knoxville TN, USA) and a double-headed gamma camera (ECAM, Siemens, Illinois, USA) for scintigraphy. The mean time difference between the two studies was 6.5 days (range: 5–8 days). Results: There was a significant difference in the detection of pulmonary and nonpulmonary sarcoidosis lesions between planar 67Ga citrate scans and 18F-FDG-PET images (<0.0021). A total of 64 lesions were detected with 67Ga citrate scans in the thorax and elsewhere with a mean of 2.6 lesions (4%) per patient, while 85 lesions were found with 18F-FDG-PET, with a mean of 3.5 lesions (4.1%) per patient. There was complete agreement between 18F-FDG and 67Ga citrate in thoracic manifestations in four (16.6%) patients, and in non-thoracic manifestations in five (20.8%) patients. The interobserver variability showed a kappa value of 0.79. Conclusion: 67Ga citrate and 18F-FDG are useful tracers for diagnostic evaluation of thoracic sarcoidosis. 18F-FDG seems to be more suitable for imaging the mediastinum, the bi-hilar lymph nodes, the posterior regions of the lungs and non-thoracic lesions. Further prospective studies are needed to clarify the role of both tracers in early diagnosis and staging of sarcoidosis, and to resolve questions concerning medical treatment and follow-up.

scholarly journals Dealing with PET radiometabolites

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Krishna Kanta Ghosh ◽  
Parasuraman Padmanabhan ◽  
Chang-Tong Yang ◽  
Sachin Mishra ◽  
Christer Halldin ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Distribution Patterns ◽  
The Body ◽  
Analysis Process ◽  
Pet Tracer ◽  
Positron Emission ◽  
Structural Identity ◽  
Available Technology ◽  
Living Organisms ◽  
Entire Amount

Abstract Positron emission tomography (PET) offers the study of biochemical, physiological, and pharmacological functions at a cellular and molecular level. The performance of a PET study mostly depends on the used radiotracer of interest. However, the development of a novel PET tracer is very difficult, as it is required to fulfill a lot of important criteria. PET radiotracers usually encounter different chemical modifications including redox reaction, hydrolysis, decarboxylation, and various conjugation processes within living organisms. Due to this biotransformation, different chemical entities are produced, and the amount of the parent radiotracer is declined. Consequently, the signal measured by the PET scanner indicates the entire amount of radioactivity deposited in the tissue; however, it does not offer any indication about the chemical disposition of the parent radiotracer itself. From a radiopharmaceutical perspective, it is necessary to quantify the parent radiotracer’s fraction present in the tissue. Hence, the identification of radiometabolites of the radiotracers is vital for PET imaging. There are mainly two reasons for the chemical identification of PET radiometabolites: firstly, to determine the amount of parent radiotracers in plasma, and secondly, to rule out (if a radiometabolite enters the brain) or correct any radiometabolite accumulation in peripheral tissue. Besides, radiometabolite formations of the tracer might be of concern for the PET study, as the radiometabolic products may display considerably contrasting distribution patterns inside the body when compared with the radiotracer itself. Therefore, necessary information is needed about these biochemical transformations to understand the distribution of radioactivity throughout the body. Various published review articles on PET radiometabolites mainly focus on the sample preparation techniques and recently available technology to improve the radiometabolite analysis process. This article essentially summarizes the chemical and structural identity of the radiometabolites of various radiotracers including [11C]PBB3, [11C]flumazenil, [18F]FEPE2I, [11C]PBR28, [11C]MADAM, and (+)[18F]flubatine. Besides, the importance of radiometabolite analysis in PET imaging is also briefly summarized. Moreover, this review also highlights how a slight chemical modification could reduce the formation of radiometabolites, which could interfere with the results of PET imaging. Graphical abstract

Galectin-3 is modulated in pancreatic cancer cells under hypoxia and nutrient deprivation

2020 ◽  
Vol 401 (10) ◽  
pp. 1153-1165 ◽  
Author(s):  
Antônio F. da Silva Filho ◽  
Lucas B. Tavares ◽  
Maira G. R. Pitta ◽  
Eduardo I. C. Beltrão ◽  
Moacyr J. B. M. Rêgo
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Ductal Adenocarcinoma ◽  
Reverse Transcription Pcr ◽  
Pancreatic Cancer Cells ◽  
Through Flow ◽  
Galectin 3

AbstractPancreatic ductal adenocarcinoma is one of the most aggressive tumors with a microenvironment marked by hypoxia and starvation. Galectin-3 has been evaluated in solid tumors and seems to present both pro/anti-tumor effects. So, this study aims to characterize the expression of Galectin-3 from pancreatic tumor cells and analyze its influence for cell survive and motility in mimetic microenvironment. For this, cell cycle and cell death were accessed through flow cytometry. Characterization of inside and outside Galectin-3 was performed through Real-Time Quantitative Reverse Transcription PCR (qRT-PCR), immunofluorescence, Western blot, and ELISA. Consequences of Galectin-3 extracellular inhibition were investigated using cell death and scratch assays. PANC-1 showed increased Galectin-3 mRNA expression when cultivated in hypoxia for 24 and 48 h. After 24 h in simultaneously hypoxic/deprived incubation, PANC-1 shows increased Galectin-3 protein and secreted levels. For Mia PaCa-2, cultivation in deprivation was determinant for the increasing in Galectin-3 mRNA expression. When cultivated in simultaneously hypoxic/deprived condition, Mia PaCa-2 also presented increasing for the Galectin-3 secreted levels. Treatment of PANC-1 cells with lactose increased the death rate when cells were incubated simultaneously hypoxic/deprived condition. Therefore, it is possible to conclude that the microenvironmental conditions modulate the Galectin-3 expression on the transcriptional and translational levels for pancreatic cancer cells.

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