POSITRON EMISSION TOMOGRAPHY-GUIDED VOLUMETRIC RESECTION OF SUPRATENTORIAL HIGH-GRADE GLIOMAS

Neurosurgery ◽  
2009 ◽  
Vol 64 (3) ◽  
pp. 471-481 ◽  
Author(s):  
Benoit J.M. Pirotte ◽  
Marc Levivier ◽  
Serge Goldman ◽  
Nicolas Massager ◽  
David Wikler ◽  
...  

Abstract OBJECTIVE Integrating positron emission tomographic (PET) images into the image-guided resection of high-grade gliomas (HGG) has shown that metabolic information on tumor heterogeneity and distribution are useful for planning surgery, improve tumor delineation, and provide a final target contour different from that obtained with magnetic resonance imaging (MRI) alone in about 80% of the procedures. Moreover, PET guidance helps to increase the amount of tumor removed and to target image-guided resection to anaplastic tissue areas. The present study aims to evaluate whether PET-guided volumetric resection (VR) in supratentorial HGG might add benefit to the patient's outcome. METHODS PET images using [18F]fluorodeoxyglucose (n=23) and [11C]methionine (n=43) were combined with MRI scans in the planning of VR procedures performed at the initial stage in 66 consecutive patients (43 M/23 F) with supratentorial HGG according to the technique previously described. In all cases (35 anaplastic gliomas [20 astrocytomas, 10 oligoastrocytomas, 5 oligodendrogliomas] and 31 glioblastomas [GBM]), level and distribution of PET tracer uptake were analyzed to define a PET contour projected on MRI scans to define a final target contour for VR. Maximal tumor resection was accomplished in each case, with the intention to remove the entire abnormal metabolic area comprised in the surgical planning. Early postoperative MRI and PET assessed tumor resection. Survival analysis was performed separately in anaplastic gliomas and glioblastoma multiforme according to the presence or absence of residual tracer uptake on postoperative PET and according to the presence or absence of residual contrast enhancement on postoperative MRI. RESULTS Preoperatively, metabolic information helped the surgical planning. In all procedures, PET contributed to define a final target contour different from that obtained with MRI alone. Postoperatively, 46 of 66 patients had no residual PET tracer uptake (total PET resection), 23 of 66 had no residual MRI contrast enhancement. No additional neurological morbidity due to the technique was reported. A total PET tracer uptake resection was associated with a significantly longer survival in anaplastic gliomas (P = 0.0071) and in glioblastoma multiforme (P = 0.0001), respectively. A total MRI contrast enhancement resection was not correlated with a significantly better survival, neither in anaplastic gliomas (P = 0.6089) nor in glioblastoma multiforme (P = 0.6806). CONCLUSIONS Complete resection of the increased PET tracer uptake prolongs the survival of HGG patients. Because PET information represents a more specific marker than MRI enhancement for detecting anaplastic tumor tissue, PET-guidance increases the amount of anaplastic tissue removed in HGG.

2006 ◽  
Vol 104 (2) ◽  
pp. 238-253 ◽  
Author(s):  
Benoît Pirotte ◽  
Serge Goldman ◽  
Olivier Dewitte ◽  
Nicolas Massager ◽  
David Wikler ◽  
...  

Object The aim of this study was to evaluate the integration of positron emission tomography (PET) scanning data into the image-guided resection of brain tumors. Methods Positron emission tomography scans obtained using fluorine-18 fluorodeoxyglucose (FDG) and l-[methyl-11C]methionine (MET) were combined with magnetic resonance (MR) images in the navigational planning of 103 resections of brain tumors (63 low-grade gliomas [LGGs] and 40 high-grade gliomas [HGGs]). These procedures were performed in 91 patients (57 males and 34 females) in whom tumor boundaries could not be accurately identified on MR images for navigation-based resection. The level and distribution of PET tracer uptake in the tumor were analyzed to define the lesion contours, which in turn yielded a PET volume. The PET scanning–demonstrated lesion volume was subsequently projected onto MR images and compared with MR imaging data (MR volume) to define a final target volume for navigation-based resection—the tumor contours were displayed in the microscope’s eyepiece. Maximal tumor resection was accomplished in each case, with the intention of removing the entire area of abnormal metabolic activity visualized during surgical planning. Early postoperative MR imaging and PET scanning studies were performed to assess the quality of tumor resection. Both pre- and postoperative analyses of MR and PET images revealed whether integrating PET data into the navigational planning contributed to improved tumor volume definition and tumor resection. Metabolic information on tumor heterogeneity or extent was useful in planning the surgery. In 83 (80%) of 103 procedures, PET studies contributed to defining a final target volume different from that obtained with MR imaging alone. Furthermore, FDG-PET scanning, which was performed in a majority of HGG cases, showed that PET volume was less extended than the MR volume in 16 of 21 cases and contributed to targeting the resection to the hypermetabolic (anaplastic) area in 11 (69%) of 16 cases. Performed in 59 LGG cases and 23 HGG cases, MET-PET demonstrated that the PET volume did not match the MR volume and improved the tumor volume definition in 52 (88%) of 59 and 18 (78%) of 23, respectively. Total resection of the area of increased PET tracer uptake was achieved in 54 (52%) of 103 procedures. Conclusions Imaging guidance with PET scanning provided independent and complementary information that helped to assess tumor extent and plan tumor resection better than with MR imaging guidance alone. The PET scanning guidance could help increase the amount of tumor removed and target image-guided resection to tumor portions that represent the highest evolving potential.


Author(s):  
Mia Ståhle ◽  
Sanna Hellberg ◽  
Jenni Virta ◽  
Heidi Liljenbäck ◽  
Olli Metsälä ◽  
...  

Activation of glucagon-like peptide-1 receptor (GLP-1R) signaling attenuates development of atherosclerosis and vascular inflammation. However, the expression of GLP-1R in atherosclerotic arteries remains uncertain. We evaluated whether a positron emission tomography (PET) tracer 68Ga-NODAGA-exendin-4 enables detection and imaging of GLP-1R expression in the mouse atherosclerotic aorta. Hypercholesterolemic (LDLR-/-ApoB100/100), hypercholesterolemic and diabetic (IGF-II/LDLR-/-ApoB100/100) as well as healthy control (C57BL/6N) mice were utilized in the study. The uptake of 68Ga-NODAGA-exendin-4 in atherosclerotic lesions was studied by autoradiography of tissue sections followed by immunofluorescence evaluation of inflammatory and vascular cell markers and GLP-1R. A subset of mice was imaged with 68Ga-NODAGA-exendin-4 PET/computed tomography (CT). The aortas of both LDLR-/-ApoB100/100 and IGF-II/LDLR-/-ApoB100/100 mice contained prominent, macrophage-rich atherosclerotic lesions. Diabetic mice demonstrated hyperglycemia and glucose intolerance. We found that by autoradiography, 68Ga-NODAGA-exendin-4 uptake was focally increased in macrophage-rich lesion areas compared with corresponding healthy vessel wall (lesion-to-wall ratio 1.6 ± 0.10, p<0.0001) in both non-diabetic and diabetic hypercholesterolemic mice. Pre-injection of unlabeled exendin-4 peptide significantly reduced cellular uptake of 68Ga-NODAGA-exendin-4. Furthermore, PET/CT imaging showed 68Ga-NODAGA-exendin-4 accumulation in the atherosclerotic aorta. Immunofluorescence stainings demonstrated co-localization of GLP-1R with macrophage-rich areas in atherosclerotic lesions. Tracer uptake was low in the healthy vessel wall of C57BL/6N mice coupled with negative GLP-1R staining. In conclusion, 68Ga-NODAGA-exendin-4 detects GLP-1R expression in atherosclerotic lesions in both non-diabetic and diabetic hypercholesterolemic mice. These results provide evidence that GLP-1R expression is mainly localized in macrophage-rich area in atherosclerotic lesions and may have implications for studies of pharmacological modification of GLP-1R signaling in atherosclerosis.


2013 ◽  
Vol 33 (5) ◽  
pp. 724-731 ◽  
Author(s):  
Stefanie Geisler ◽  
Antje Willuweit ◽  
Michael Schroeter ◽  
Karl Zilles ◽  
Kurt Hamacher ◽  
...  

After cerebral ischemia or trauma, secondary neurodegeneration may occur in brain regions remote from the lesion. Little is known about the capacity of cerebral gliomas to induce secondary neurodegeneration. A previous study showed that cis-4-[18F]fluoro-D-proline (D- cis-[18F]FPro) detects secondary reactions of thalamic nuclei after cortical infarction with high sensitivity. Here we investigated the potential of D- cis-[18F]FPro to detect neuronal reactions in remote brain areas in the F98 rat glioma model using ex vivo autoradiography. Although the tumor tissue of F98 gliomas showed no significant D- cis-[18F]FPro uptake, we observed prominent tracer uptake in 7 of 10 animals in the nuclei of the ipsilateral thalamus, which varied with the specific connectivity with the cortical areas affected by the tumor. In addition, strong D- cis-[18F]FPro accumulation was noted in the hippocampal area CA1 in two animals with ipsilateral F98 gliomas involving hippocampal subarea CA3 rostral to that area. Furthermore, focal D- cis-[18F]FPro uptake was present in the necrotic center of the tumors. Cis-4-[18F]fluoro-D-proline uptake was accompanied by microglial activation in the thalamus, in the hippocampus, and in the necrotic center of the tumors. The data suggest that brain tumors induce secondary neuronal reactions in remote brain areas, which may be detected by positron emission tomography (PET) using D- cis-[18F]FPro.


2021 ◽  
Vol 14 (8) ◽  
pp. 745
Author(s):  
Jonathan Cotton ◽  
Chris Marc Goehring ◽  
Anna Kuehn ◽  
Andreas Maurer ◽  
Kerstin Fuchs ◽  
...  

The acidic hydrolase α-fucosidase (AF) is a biomarker for maladies such as cancer and inflammation. The most advanced probes for α-fucosidase are unfortunately constrained to ex vivo or in vitro applications. The in vivo detection and quantification of AF using positron emission tomography would allow for better discovery and diagnosis of disease as well as provide better understanding of disease progression. We synthesized, characterized, and evaluated a radiolabeled small molecule inhibitor of AF based on a known molecule. The radiosynthesis involved the 11C methylation of a phenoxide, which was generated in situ by ultrasonification of the precursor with sodium hydride. The tracer was produced with a decay corrected yield of 41.7 ± 16.5% and had a molar activity of 65.4 ± 30.3 GBq/μmol. The tracer was shown to be stable in mouse serum at 60 min. To test the new tracer, HCT116 colorectal carcinoma cells were engineered to overexpress human AF. In vitro evaluation revealed 3.5-fold higher uptake in HCT116AF cells compared to HCT116 controls (26.4 ± 7.8 vs. 7.5 ± 1.0 kBq/106 cells). Static PET scans 50 min post injection revealed 2.5-fold higher tracer uptake in the HCT116AF tumors (3.0 ± 0.8%ID/cc (n = 6)) compared with the controls (1.2 ± 0.8 (n = 5)). Dynamic scans showed higher uptake in the HCT116AF tumors at all time-points (n = 2). Ex vivo analysis of the tumors, utilizing fluorescent DDK2 antibodies, confirmed the expression of human AF in the HCT116AF xenografts. We have developed a novel PET tracer to image AF in vivo and will now apply this to relevant disease models.


2011 ◽  
Vol 10 (6) ◽  
pp. 7290.2011.00014 ◽  
Author(s):  
Norbert Galldiks ◽  
Lutz W. Kracht ◽  
Veronika Dunkl ◽  
Roland T. Ullrich ◽  
Stefan Vollmar ◽  
...  

In patients with World Health Organization (WHO) grade III glioma with a lack of or minimal (< 1 cm3) magnetic resonance imaging (MRI) contrast enhancement, the volume of the metabolically active part of the tumor was assessed by [ 11 C]-methionine positron emission tomography (MET-PET). Eleven patients with WHO grade III gliomas underwent MET-PET and MRI (contrast-enhanced T1-and T2-weighted images). To calculate the volumes in cubic centimeters, threshold-based volume of interest analyses of the metabolically active tumor (MET uptake index ≥ 1.3), contrast enhancement, and the T2 lesion were performed after coregistration of all images. In all patients, the metabolically active tumor volume was larger than the volume of gadolinium–diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement (20.8 ± 18.8 vs 0.29 ± 0.25 cm3; p < .001). With the exception of one patient, the volumes of contrast enhancement were located within the metabolically active tumor volume. In contrast, in the majority of patients, MET uptake overlapped with the T<sb>2 lesion and reached beyond it (in 10 of 12 MRIs/MET-PET scans). The present data suggest that in patients with WHO grade III glioma with minimal or a lack of contrast enhancement, MET-PET delineates metabolically active tumor tissue. These findings support the use of combined PET-MRI with radiolabeled amino acids (eg, MET) for the delineating of the true extent of active tumor in the diagnosis and treatment planning of patients with gliomas.


2005 ◽  
Vol 57 (suppl_1) ◽  
pp. 128-139 ◽  
Author(s):  
Benoit Pirotte ◽  
Serge Goldman ◽  
Patrick Van Bogaert ◽  
Philippe David ◽  
David Wikler ◽  
...  

Abstract OBJECTIVE: To evaluate the interest of integrating positron emission tomography (PET) images with the radiolabeled tracer [11C]methionine (Met) into the image-guided navigation planning of infiltrative low-grade brain tumors (LGBTs) in children. METHODS: Twenty-two children underwent combined Met-PET with magnetic resonance imaging (MRI) scans in the planning of a navigation procedure. These children presented an LGBT (astrocytomas, 10; oligodendrogliomas, 4; ependymomas, 4; gangliogliomas, 4) located close to functional areas. Tumor boundaries were ill-defined on MRI (including T2-weighted and fluid-attenuated inversion-recovery scans) and could not be clearly identified for allowing a complete, or at least a large, image-guided resection. The PET tracer Met was chosen because of its higher sensitivity and specificity than MRI to detect tumor tissue. The level and extension of MET uptake were analyzed to define the PET contour, subsequently projected onto MRI scans to define a final target contour for volumetric resection. The quality of tumor resection was assessed by an early postoperative MRI and Met-PET workup. RESULTS: In 20 of the 22 children with ill-defined LGBTs, PET improved tumor delineation and contributed to define a final target contour different from that obtained with MRI alone. Met-PET guidance allowed a total resection of Met uptake in 17 cases that were considered total tumor resections because the operative margin left in place contained nontumor tissue. CONCLUSION: These data suggested that Met-PET guidance could help to improve the number of total resections and the amount of tumor removed in infiltrative LGBTs in children.


2020 ◽  
Vol 6 (4) ◽  
pp. 20200024
Author(s):  
Enrico M Novelli ◽  
Chan Hong Moon ◽  
Tiffany A Pham ◽  
Lydia A Perkins ◽  
Lynda Little-Ihrig ◽  
...  

Increased vascular cell adhesion (hyperadhesion) to the endothelium is responsible for the hallmark acute pain episodes, or vaso-occlusive crises (VOC), of sickle cell disease. The integrin αvβ3 plays an important role in VOC since it mediates sickle red blood cell adhesion to the endothelium, a process that leads to ischemia and painful bone infarction. In the pilot study presented herein, we hypothesized that real-time imaging of hyperadhesion could quantify VOC severity and identify the most vulnerable anatomical sites. We also hypothesized that harnessing hyperadhesion as a proximate event in VOC would provide sensitive, objective evidence of VOC before pain has developed. Specifically, we tested whether positron emission tomography (PET) imaging of integrin αvβ3 using the PET tracer 68Ga-PRGD2 would successfully image hyperadhesion associated with VOC in a patient with sickle cell disease. We observed persistently higher tracer uptake in the femurs during VOC compared to baseline. In the vessel, after an initial and transient increase during VOC, blood pool activity was similar between baseline and VOC. These findings suggest that PET imaging of integrin αvβ3 may be a valuable strategy for imaging of VOC.


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