Reproducibility of O-(2-18F-fluoroethyl)-L-tyrosine uptake kinetics in brain tumors and influence of corticoid therapy: an experimental study in rat gliomas

Stegmayr, Carina; Schöneck, Michael; Oliveira, Dennis; Willuweit, Antje; Filß, Christian; Galldiks, Norbert; Shah, N. Jon; Coenen, Heinz H.; Langen, Karl‐Josef

doi:10.1007/s00259-015-3274-4

Cited by 19 publications

(59 citation statements)

References 36 publications

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“…MBq 68 Ga-PSMA or 18 F-DCFPyL, respectively ( Table 1). Five animals for each tracer and each tumor model were additionally investigated by micro-PET using a small animal Siemens INVEON scanner as described previously [18]. The PET measurement was performed during accumulation phase of the tracers from 20-40 min postinjection.…”

Section: Autoradiography and Micro-petmentioning

confidence: 99%

“…For the AR, animals were sacrificed, rat brains removed and immediately frozen in liquid isopentane (-50 C). Every tenth slice of the 20 μm cryosections of the tumor bearing brain and freshly prepared 20 μm 68 Ga and 18 F standards, to generate a tracer calibration curve, were exposed to an imaging plate (Fuji Imaging Plate, Raytest) overnight , scanned (Fuji BAS Reader 5000, Raytest) and quantitatively evaluated with a pixel size of 25 μm (AIDA Version 4.50, Raytest). Tracer uptake in the tissue was expressed as standardized uptake value (SUV) by dividing the radioactivity (kBq/ml) in the tissue by the radioactivity injected per gram of body weight.…”

Section: Autoradiography and Micro-petmentioning

confidence: 99%

“…Competition tests were performed with four animals to evaluate binding specificity of 68 Ga-PSMA (n=2) and 18 F-DCFPyL (n=2). As competitor 30 mg/kg BW 2-(Phosphonomethyl)pentane-1,5-dioic acid (PMPA; Tocris) was co-injected i.v.…”

Section: Pharmacological Interventionsmentioning

confidence: 99%

“…The evaluation of PET data was performed as described previously [18]. Tumor VOI and contralateral background VOI (110 mm³) were placed for each animal in summed PET images from 20 to 40 min p.i..…”

Section: Data Evaluationmentioning

confidence: 99%

“…PET ligands for the prostate specific membrane antigen (PSMA) are very successful in the diagnostic 4 assessment of prostate cancer [1,2]. The most widely studied agent is the 68 Ga-labelled PSMA inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ( 68 Ga-PSMA) but in recent years 18 F-labelled ligands such as 2-(3-(1-carboxy-5-[(6-[ 18 F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid ( 18 F-DCFPyL) have been developed which show advantages with respect to production amount, availability, clinical utility, and image resolution [3,4]. PSMA is also expressed by a variety of nonprostate cancers, often on the endothelium of tumor-associated neovasculature [5] and initial studies have explored the application of PSMA ligands in breast, lung, bladder, pancreatic and colorectal cancer, renal cell carcinoma and glioblastoma [6].…”

Section: Introductionmentioning

confidence: 99%

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High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes

Oliveira

Stegmayr

Heinzel

et al. 2020

Preprint

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Background Recent studies reported on high uptake of the PSMA ligands [ 68 Ga]HBED-CC ( 68 Ga-PSMA) and 18 F-DCFPyL in cerebral gliomas. This study explores the regional uptake and cellular targets of 68 Ga-PSMA and 18 F-DCFPyL in three different rat glioma models. Methods F98, 9L or U87 rat gliomas were implanted into the brains of 38 rats. After 13 days of tumor growth, 68 Ga-PSMA (n=21) or 18 F-DCFPyL (n=17) were injected intravenously and animals were sacrificed 40 min later. Five animals for each tracer and tumor model were additionally investigated by micro-PET at 20-40 min postinjection. Cryosections of the tumor bearing brains were analyzed by ex vivo autoradiography and immunofluorescence staining for blood vessels, microglia, astrocytes and presence of PSMA. Blood-brain barrier (BBB) permeability was tested by coinjection of Evans blue dye (EBD). 68 Ga-PSMA uptake after restoration of BBB integrity by treatment with dexamethasone (Dex) was evaluated in four animals with U87 gliomas. Competition experiments using the PSMA-receptor inhibitor 2-(Phosphonomethyl)pentane-1,5-dioic acid (PMPA) were performed for both tracers in two animals each. Results Autoradiography demonstrated a strong 68 Ga-PSMA and 18 F-DCFPyL binding in the peritumoral area and moderate binding in the center of the tumors. PMPA administration led to complete inhibition of 68 Ga-PSMA and 18 F-DCFPyL binding in the peritumoral region. Restoration of BBB by Dex treatment reduced EBD extravasation but 68 Ga-PSMA binding remained unchanged. Expression of activated microglia (CD11b) was low in the intra- and peritumoral area but GFAP staining revealed strong activation of astrocytes in congruency to the tracer binding in the peritumoral area. All tumors were visualized in micro PET, showing a lower tumor/brain contrast with 68 Ga-PSMA than with 18 F-DCFPyL. Conclusions High uptake of 68 Ga-PSMA and 18 F-DCFPyL in the peritumoral area of all glioma models is presumably caused by activated astrocytes. This may represent a limitation for the clinical application of PSMA ligands in gliomas.

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Section: Autoradiography and Micro-petmentioning

confidence: 99%

Section: Autoradiography and Micro-petmentioning

confidence: 99%

Section: Pharmacological Interventionsmentioning

confidence: 99%

Section: Data Evaluationmentioning

confidence: 99%