18f-fluoroethyl-l-tyrosine and Disease-Models--Animal

Glioblastoma (GB) is the most common primary malignant brain tumor. Standard medical treatment consists of a maximal safe surgical resection, subsequently radiation therapy (RT) and chemotherapy with temozolomide (TMZ). An accurate definition of the tumor volume is of utmost importance for guiding RT. In this project we investigated the feasibility and treatment response of subvolume boosting to a PET-defined tumor part.. F98 GB cells inoculated in the rat brain were imaged using T2- and contrast-enhanced T1-weighted (T1w) MRI. A dose of 20 Gy (5 × 5 mm. When comparing the dose volume histograms, a significant difference was found exclusively between the D. In this study we showed the feasibility of PET guided subvolume boosting of F98 glioblastoma in rats. No evidence was found for a beneficial effect regarding tumor response. However, improvements for dose targeting in rodents and studies investigating new targeted drugs for GB treatment are mandatory.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Disease Models, Animal; Feasibility Studies; Female; Glioblastoma; Nitroimidazoles; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy, Image-Guided; Rats, Inbred F344; Treatment Outcome; Tumor Burden; Tyrosine

The extent of surgical resection is significantly correlated with outcome in glioma; however, current intraoperative navigational tools are useful only in a subset of patients. We show here that a new optical intraoperative technique, Cerenkov luminescence imaging (CLI) following intravenous injection of O‑(2-[

Topics: Administration, Intravenous; Animals; Brain Neoplasms; Disease Models, Animal; Glioma; Heterografts; Histocytochemistry; Luminescent Measurements; Neoplasm Transplantation; Rats; Surgery, Computer-Assisted; Treatment Outcome; Tyrosine

(S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.. For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.. In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.. 18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.. ClinicalTrials.gov NCT01186601.

Topics: Adult; Aged; Animals; Brain Neoplasms; Case-Control Studies; Cell Line, Tumor; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Glioblastoma; Glutamic Acid; Heterografts; Humans; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Tomography, X-Ray Computed; Tyrosine

Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results.. Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed.. The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p = 0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN.. Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN.

Topics: Animals; Brain; Cell Line, Tumor; Choline; Diagnosis, Differential; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Glioblastoma; Humans; Kinetics; Necrosis; Neoplasm Grading; Positron-Emission Tomography; Radiation Injuries; Radiopharmaceuticals; Rats, Inbred F344; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

O-(2'-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of (18)F (110min) allowing remote-site application. Here we present a novel type of chiral enantiomerically pure labeling precursor for [(18)F]FET, based on NiII complex of a Schiff's base of (S)-[N-2-(N'-benzylprolyl)amino]benzophenone (BPB) with alkylated (S)-tyrosine, Ni-(S)-BPB-(S)-Tyr-OCH2CH2X (X=OTs (3a), OMs (3b) and OTf (3c)). A series of compounds 3a-c was synthesized in three steps from commercially available reagents. Non-radioactive FET as a reference was prepared from 3a in a form of (S)-isomer and (R,S) racemic mixture. Radiosynthesis comprised two steps: (1) n.c.a. nucleophilic fluorination of 3a-c (4.5-5.0mg) in the presence of either Kryptofix 2.2.2.or tetrabutylammonium carbonate (TBAC) in MeCN at 80 degrees C for 5min, followed by (2) removal of protective groups by treating with 0.5M HCl (120 degrees C, 5min). The major advantages of this procedure are retention of enantiomeric purity during the (18)F-introduction step and easy simultaneous deprotection of amino and carboxy moieties in 3a-c. Radiochemically pure [(18)F]FET was isolated by semi-preparative HPLC (C18 mu-Bondapak, Waters) eluent aq 0.01M CH(3)COONH(4), pH 4/C(2)H(5)OH 90/10 (v/v). Overall synthesis time operated by Anatech RB 86 laboratory robot was 55min. In a series of compounds 3a-c, tosyl derivative 3a provided highest radiochemical yield (40-45%, corrected for radioactive decay). Enantiomeric purity was 94-95% and 96-97%, correspondingly, for Kryptofix and TBAC assisted fluorinations. The suggested procedure involved minimal number of synthesis steps and suits perfectly for automation in the modern synthesis modules for PET radiopharmaceuticals. Preliminary biodistribution study in experimental model of turpentine-induced aseptic abscess and Glioma35 rat's tumor (homografts) in Wistar rats has demonstrated the enhanced uptake of radiotracer in the tumor area with minimal accumulation in the inflamed tissues.

Topics: Animals; Benzophenones; Chromatography, High Pressure Liquid; Disease Models, Animal; Glioma; Molecular Conformation; Nickel; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Wistar; Schiff Bases; Skin Neoplasms; Stereoisomerism; Tyrosine