fluorocholine and Glioblastoma

Glioblastoma multiforme (GBM) represents the most common and malignant glioma, accounting for 45%-50% of all gliomas. The median survival time for patients with glioblastoma is only 12-15 months after surgical, chemioterapic and radiotherapic treatment; a correct diagnosis is naturally fundamental to establish a rapid and correct therapy. Non-invasive imaging plays a pivotal role in each phase of the diagnostic workup of patients with suspected for diagnosis. The aim of this case report was to describe the potential clinical impact of 18F-fluorocholine (FCH) PET/CT in the assessment of a cystic GBM mimicking a spontaneous hemorrhage.. a 57 years-old male with intraparenchymal hemorrhage at CT imaging initially in reduction ad serial imaging and suspected right fronto-temporo-parietal lesion at MRI underwent dynamic and static (60' after tracer injection) FCH PET/CT of the brain.. FCH PET/CT showed rapid tracer uptake after few second from injection at dynamic acquisition and consequent incremental mild uptake at static imaging after 60 minutes at the level of oval formation in the right cerebral hemisphere characterized by annular and peripheral high metabolic activity. The central region of the lesion was characterized by the absence 18F-FCH uptake most likely due to blood component. The patient underwent surgery for tumor removal; the histopathological examination confirmed the suspect of GBM. Chemo-radiotherapic adjuvant protocol according to Stupp protocol was therefore administrated; to date the patient is alive without any progression disease at 5 months from treatment.. In this case report FCH PET/CT represented the final diagnostic technique to confirm the suspicious of a cystic GBM. Our case demonstrated the potential role of 18F-FCH PET/CT for discrimination of higher proliferation area over intraparenchymal hemorrhage, supporting the potential use of this imaging biomarker in surgical or radiosurgical approach. Obviously, further prospective studies are needed to confirm this role and to exactly define possible routinely applications.

Topics: Brain Neoplasms; Cerebral Hemorrhage; Choline; Diagnosis, Differential; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals

The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon is important in order to choose the best therapy and predict the prognosis but is still a big problem for physicians. The new emerging MRI, CT, and PET diagnostic modalities still lack sufficient accuracy. Radiolabeled choline and amino acids have been reported to show great tumor specificity. We studied the uptake kinetics of [

Topics: Carbon; Cell Line, Tumor; Choline; Diagnosis, Differential; Glioblastoma; Humans; Ions; Neoplasm Metastasis; Photons; Tyrosine

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Choline; Disease Models, Animal; Fluorodeoxyglucose F18; Glioblastoma; Heterografts; Humans; Image Processing, Computer-Assisted; Luminescent Measurements; Mice; Positron-Emission Tomography; Radiopharmaceuticals

Tumor and chemo/radiotherapy-damaged brain tissues are hardly distinguishable by conventional morphological imaging. (18)F-FCH was compared against (18)F-FDG in the T98G glioblastoma cell line with regard to their radiopharmaceutical uptake, in order to test its diagnostic power on brain tumor lesions.. Equimolar amounts of (18)F-FCH and (18)F-FDG were added to human glioblastoma T98G cells and human dermal fibroblasts for 20, 40, 60, 90 and 120 min of incubation. Radiopharmaceutical uptake was expressed as a percentage of the administered dose. Cold choline was used for binding competition experiments.. In T98G cells (18)F-FCH was taken-up in higher amounts than 18F-FDG after 60 min. In fibroblasts, uptake was lower than 1% for both radiopharmaceuticals. Cold choline reduced the uptake of FCH to 1% similarly to fibroblasts.. Our results prove the efficacy of (18)F-FCH as a promising tracer, better than (18)F-FDG in establishing the tumor-to-background ratio in brain tumors.

Topics: Brain Neoplasms; Cell Line, Tumor; Choline; Fluorodeoxyglucose F18; Glioblastoma; Humans; Radionuclide Imaging; Radiopharmaceuticals

Primary brain tumors (PBT), in particular gliomas, are among the most difficult neoplasms to treat, necessitating good quality imaging to guide clinicians at many junctures. Current imaging modalities, including [18F] fluorodeoxyglucose (FDG) PET/CT, MRI and MR spectroscopy (MRS), have various limitations, particularly with regard to differentiating tumor from radiation induced necrosis (RIN) and from normal cerebral metabolic uptake. [18F] fluorocholine (FCH) is an analog of choline with potentially optimal imaging characteristics, as pharmacokinetic studies with FCH conducted in patients showed minimal FCH uptake by normal brain parenchyma, whereas high-grade tumors are known to have increased choline uptake. We present two cases of our early experience with FCH PET/CT for patients with PBT and discuss the potential use and comparative limitations of this imaging modality.

Topics: Brain Neoplasms; Choline; Fatal Outcome; Female; Fluorine Radioisotopes; Glioblastoma; Glioma; Humans; Magnetic Resonance Imaging; Middle Aged; Neoplasm Recurrence, Local; Oligodendroglioma; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed

Multidrug resistance, aggressiveness and accelerated choline metabolism are hallmarks of malignancy and have motivated the development of new PET tracers like (18)F-FCH, an analogue of choline. Our aim was to study the relationship of multidrug resistance of cultured glioma cell lines and (18)F-FCH tracer uptake.. We used an in vitro multidrug-resistant (MDR) glioma model composed of sensitive parental U87MG and derived resistant cells U87MG-CIS and U87MG-DOX. Aggressiveness, choline metabolism and transport were studied, particularly the expression of choline kinase (CK) and high-affinity choline transporter (CHT1). FCH transport studies were assessed in our glioblastoma model.. As expected, the resistant cell lines express P-glycoprotein (Pgp), multidrug resistance-associated protein isoform 1 (MRP1) and elevated glutathione (GSH) content and are also more mobile and more invasive than the sensitive U87MG cells. Our results show an overexpression of CK and CHT1 in the resistant cell lines compared to the sensitive cell lines. We found an increased uptake of FCH (in % of uptake per 200,000 cells) in the resistant cells compared to the sensitive ones (U87MG: 0.89 +/- 0.14; U87MG-CIS: 1.27 +/- 0.18; U87MG-DOX: 1.33 +/- 0.13) in line with accelerated choline metabolism and aggressive phenotype.. FCH uptake is not influenced by the two ATP-dependant efflux pumps: Pgp and MRP1. FCH would be an interesting probe for glioma imaging which would not be effluxed from the resistant cells by the classic MDR ABC transporters. Our results clearly show that FCH uptake reflects accelerated choline metabolism and is related to tumour aggressiveness and drug resistance.

Topics: Animals; Biological Transport; Cell Line, Tumor; Choline; Choline Kinase; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Phenotype; Symporters