Multimodal Imaging of Patients With Gliomas Confirms 11C-MET PET as a Complementary Marker to MRI for Noninvasive Tumor Grading and Intraindividual Follow-Up After Therapy.

The value of combined L-( methyl-[11C]) methionine positron-emitting tomography (MET-PET) and magnetic resonance imaging (MRI) with regard to tumor extent, entity prediction, and therapy effects in clinical routine in patients with suspicion of a brain tumor was investigated. In n = 65 patients with histologically verified brain lesions n = 70 MET-PET and MRI (T1-weighted gadolinium-enhanced [T1w-Gd] and fluid-attenuated inversion recovery or T2-weighted [FLAIR/T2w]) examinations were performed. The computer software "visualization and analysis framework volume rendering engine (Voreen)" was used for analysis of extent and intersection of tumor compartments. Binary logistic regression models were developed to differentiate between World Health Organization (WHO) tumor types/grades. Tumor sizes as defined by thresholding based on tumor-to-background ratios were significantly different as determined by MET-PET (21.6 ± 36.8 cm3), T1w-Gd-MRI (3.9 ± 7.8 cm3), and FLAIR/T2-MRI (64.8 ± 60.4 cm3; P < .001). The MET-PET visualized tumor activity where MRI parameters were negative: PET positive tumor volume without Gd enhancement was 19.8 ± 35.0 cm3 and without changes in FLAIR/T2 10.3 ± 25.7 cm3. FLAIR/T2-MRI visualized greatest tumor extent with differences to MET-PET being greater in posttherapy (64.6 ± 62.7 cm3) than in newly diagnosed patients (20.5 ± 52.6 cm3). The binary logistic regression model differentiated between WHO tumor types (fibrillary astrocytoma II n = 10 from other gliomas n = 16) with an accuracy of 80.8% in patients at primary diagnosis. Combined PET and MRI improve the evaluation of tumor activity, extent, type/grade prediction, and therapy-induced changes in patients with glioma and serve information highly relevant for diagnosis and management.

Evaluation of 131I scintigraphy and stimulated thyroglobulin levels in the follow up of patients with DTC: a retrospective analysis of 1420 patients.

AIM: To study the clinical yield of diagnostic whole body 131I scintigraphy (DxWBS) in the follow-up of differentiated thyroid carcinoma (DTC) patients in relation to stimulated thyroglobulin (sTg) in the initial post-ablation setting, as well as in the setting of repeated monitoring in course of further DTC follow-up. METHODS: Data of 1420 thyroidectomized and radioiodine remnant-ablated DTC patients following a well-defined therapy and standardized follow-up protocol were evaluated. DxWBS and sTg were evaluated separately and in combination for various follow-up time points. The factual administration of the recorded indication for further oncologic therapy (excluding radioiodine therapies given for minimal normal remnants) within the following 4 months after follow-up served as the standard of reference. Furthermore, DxWBS was compared to post therapy WBS and SPECT(/CT) if available. Subgroup analysis was carried out for DTC patients < 45 years old at diagnosis without distant metastasis. The diagnostic impact of cervical ultrasound was not assessed. RESULTS: sTg can identify the patients at risk better than DxWBS. Furthermore, the most sensitive time point to assess response appears to be a time point beyond 3 months after RRA. When information received from both imaging and laboratory measurements are concordant, i.e. both construe absence of remaining disease, only a small fraction of patients (<2%) required treatment in the future. The strongest effect was observed 12 months after RRA. Only 0.9% of the negative DxWBS patients with concordant sTg below the functional sensitivity at this time point required treatment thereafter. CONCLUSION: A complete omission of DxWBS in the post-RRA surveillance of DTC is justified once DxWBS is negative and sTg is below the functional sensitivity (with no evidence of thyroglobulin antibodies), as patients showing this combination of test results (especially 12 months after RRA) show an at worst marginal risk of recurrence. In all other cases DxWBS may still be justified.

Sex differences in absolute myocardial perfusion. Non-invasive H2(15)O-PET in young healthy adults.

AIM: To investigate sex differences in myocardial perfusion especially in healthy individuals since former studies are rare and findings are controversial. Participants, methods: 26 subjects were enrolled: 16 healthy women (age: 34 ±7 years) were compared with 10 healthy men (age: 34 ± 3 years; p = ns). Myocardial blood flow (MBF) and coronary vascular resistance (CVR) were quantified at rest, during adenosine infusion and cold-pressor-testing, using positron emission tomography and radioactive-labelled water (H2(15)O-PET). RESULTS: Women showed higher MBF than men at rest (1.10 ± 0.18 vs. 0.85 ± 0.20 ml/min/ml; p = 0.003) and cold-stress (1.39 ± 0.38 vs. 1.06 ± 0.28 ml/min/ml; p = 0.026). Corrected for rate-pressure-product, baseline findings maintained significance (1.41 ± 0.33 vs. 1.16 ± 0.19 ml/min/ml; p = 0.024). CVR was lower in women at baseline (81 ± 14 vs. 107 ± 22 mmHg*ml(-1)*min*ml; p = 0.006) and during cold-pressor-testing (71 ± 17 vs. 91 ± 20 mmHg*ml(-1)*min*ml; p = 0.013). Under adenosine neither maximal MBF (4.06 ± 1.0 vs. 3.91 ± 0.88 ml/min/ml; p = ns) nor coronary flow reserve (3.07 ± 1.12 vs. 3.44 ± 0.92; p = ns) nor CVR (24 ± 8 vs. 24 ± 6 mmHg*ml(-1)*min*ml; p = ns) showed sex-related differences. CONCLUSION: Women show higher myocardial perfusion and lower coronary vascular resistance than men in physiologic states. Maximum perfusion and vasodilation under adenosine are not sex-specific.

Novel fluorine-18 labeled 5-(1-pyrrolidinylsulfonyl)-7-azaisatin derivatives as potential PET tracers for in vivo imaging of activated caspases in apoptosis.

The programmed type I cell death, defined as apoptosis, is induced by complex regulated signaling pathways that trigger the intracellular activation of executioner caspases-3, -6 and -7. Once activated, these enzymes initiate cellular death through cleavage of proteins which are responsible for DNA repair, signaling and cell maintenance. Several radiofluorinated inhibitors of caspases-3 and -7, comprising a moderate lipophilic 5-(1-pyrrolidinylsulfonyl)isatin lead structure, are currently being investigated for imaging apoptosis in vivo by us and others. The purpose of this study was to increase the intrinsic hydrophilicity of the aforementioned lead structure to alter the pharmacokinetic behavior of the resulting caspase-3 and -7 targeted radiotracer. Therefore, fluorinated and non-fluorinated derivatives of 5-(1-pyrrolidinylsulfonyl)-7-azaisatin were synthesized and tested for their inhibitory properties against recombinant caspases-3 and -7. Fluorine-18 has been introduced by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of an alkyne precursor with 2-[(18)F]fluoroethylazide. Using dynamic micro-PET biodistribution studies in vivo the kinetic behavior of one promising PET-compatible 5-pyrrolidinylsulfonyl 7-azaisatin derivative has been compared to a previously described isatin based radiotracer.

Not all DTC patients with N positive disease deserve the attribution "high risk". Contribution of the MSDS trial.

BACKGROUND AND OBJECTIVES: To investigate if patients with thyroid carcinoma having N1a disease are at the same risk with N1b using the collective of the well-defined European prospective Multicentre Study Differentiated Thyroid Cancer (MSDS). METHODS: Overall (OS) and event free survival (EFS) were calculated. Cox multivariable regression analysis was performed in order to calculate Hazard ratios (HR). RESULTS: EFS was significantly decreased only in patients with N1b metastasis as compared to N0 patients and became worse when N1a was concomitantly affected. A superior survival in favor of N1a patients as compared to N1b patients with regard to EFS was also observed. The patients having N1a disease showed no differences in the EFS as compared to N0. OS did not differ significantly in any of the groups. There was an increased HR for events with regards to histology, T-stage, tumor size, UICC stage and cervical lymph node metastasis. Tumor size showed a significantly increased risk for OS. CONCLUSIONS: Patients with pT3b and pT4a tumors with N1b are of higher risk for relapse, albeit not affecting overall survival. Patients with N1a are of no higher risk. The risk stratification of these patients may be adapted accordingly.

New matrix metalloproteinase inhibitors based on γ-fluorinated α-aminocarboxylic and α-aminohydroxamic acids.

Matrix metalloproteinases (MMPs) are involved in a number of physiological as well as pathological processes such as atherosclerosis and tumorigenesis, where an up-regulation of MMPs is predominant. Fluorinated analogues of the hydroxamate-based non-peptidic broad-spectrum MMP inhibitor (MMPI) CGS 27023A were synthesized and inhibition potencies for MMP-2 and MMP-9 in the nanomolar range were measured using fluorimetric in vitro assays. The inhibition potencies of the herein reported fluorinated MMPIs were comparable or even superior in some cases to their non-fluorinated analogues. In contrast to the lead structure, both enantiomers of fluorinated MMPs were almost equally potent. Modelling studies suggest that the core α-amino hydroxamic acid residues appear to influence the relative potencies via specific inhibitor-peptidase interactions, including short fluorine-hydrogen contacts, within the enzyme's pockets. The binding of the essential hydroxamate group to the zinc ion is rather unaffected by the rest of the molecule. In contrast, the corresponding α-aminocarboxylic acid derivatives are 10(3) times less potent or were even inactive.

Differentiated thyroid cancer patients more than 60 years old paradoxically show an increased life expectancy.

UNLABELLED: The aim of this study was to compare the overall survival of a large, single-center cohort of patients who had differentiated thyroid cancer (DTC) with that of a matched general population. METHODS: We analyzed 2,428 consecutive patients who had DTC and underwent treatment from 1965 to 2013 at the Department of Nuclear Medicine, University Hospital of Münster, Münster, Germany, according to international standards. Patients were classified on the basis of the current, seventh edition of the American Joint Committee on Cancer/Union for International Cancer Control classification system. Additionally, a subgroup analysis with regard to age at diagnosis was performed. The overall survival of the patients was compared with the expected survival of the general population on the basis of age and sex, as provided by the Federal Statistical Office of Germany. RESULTS: Compared with the expected survival, the overall survival of patients with stage I disease paradoxically was significantly better (P < 0.001). In the subgroup analysis, a significantly lower mortality rate was observed in elderly patients (≥60 y old) with stage I disease. On the other hand, patients between 20 and 45 y of age and with distant metastases at diagnosis had a significantly increased standardized mortality rate. In contrast, other patients with stage II disease and more than 45 y old had a normal mortality rate. The mortality rate was significantly increased in all patients with stage IVC disease. CONCLUSION: Older patients with more limited disease paradoxically had better survival than would be expected on the basis of age and sex, whereas young adults as well as patients more than 45 y old and with distant metastases had increased mortality rates. For all other DTC patients, regardless of age or TNM stage, no significant survival difference was seen.

The diagnostic imaging of bone metastases.

BACKGROUND: Skeletal metastases are the most common malignant tumor in bone. Certain types of cancer (e.g., of the prostate or breast) are particularly likely to give rise to skeletal metastases, with prevalences of up to 70%. The diagnosis of skeletal metastases has a major impact on the overall treatment strategy and is an important determinant of the course of illness and the quality of life. The goal of diagnostic imaging is to detect skeletal metastases early, whenever they are suspected on the basis of clinical or laboratory findings or in patients who are at high risk. Other important issues include assessment of the risk of fracture and the response to treatment. METHODS: This review is based on selected pertinent articles published up to December 2013. RESULTS: Projectional radiography (plain films) is still useful for the immediate investigation of symptomatic bone pain and for the assessment of stability. Skeletal scintigraphy, the classic screening test for patients with cancer who do not have bone pain (specificity 81%, sensitivity 86%), has now been supplemented-in some cases, replaced-by other techniques. CT, including lowdose CT, is used to detect changes in bone structure due to metastases of some types of primary tumor (specificity 95%, sensitivity 73%); whole-body MRI, to detect metastases in the bone marrow and extraosseous soft tissues, e.g., metastases compressing the spinal cord (specificity 95%, sensitivity 91%); PET-CT, to detect metabolically active tumors (specificity 97%, sensitivity 90%). CONCLUSION: Different imaging modalities are often used in combination to detect bone metastases optimally. Owing to advances in modern tomographic imaging, the current trend is toward whole-body imaging in a single session. The choice of method is based on the clinical situation and the type of primary tumor. Further research should address the impact of these costly and laborintensive imaging methods on treatment strategies and on the course of illness.

Synthesis of 7-halogenated isatin sulfonamides: nonradioactive counterparts of caspase-3/-7 inhibitor-based potential radiopharmaceuticals for molecular imaging of apoptosis.

N-Alkylated (S)-7-halogen-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatins were developed as a new group of nonradioactive reference compounds for future radiotracers. Inhibitor potency studies of these compounds suggest that the binding pockets readily accommodate both the 7-halogen substituents and aliphatic side chains (methyl to n-butyl) as well as some ω-fluorinated analogues (3-fluoropropyl and 4-fluorobutyl) at the isatin nitrogen. Indeed, compared to the halogen free parent compounds, some 7-halogenated derivatives exhibited slightly improved inhibitory potencies with IC50 values up to 2.6 nM (caspase-3) and 3.3 nM (caspase-7), respectively. Moreover, the 7-position of isatin, a potential cytochrome P450 hydroxylation site, was substituted by I, Br, Cl, and F to potentially enhance the metabolic stability of isatin sulfonamides. As an example, the radiotracer [(18)F]39 that was produced by (19)F/(18)F isotope exchange was shown to be stable in human blood serum after incubation at 37 °C for at least 90 min.

Serial F-18-FDG PET/CT distinguishes inflamed from stable plaque phenotypes in shear-stress induced murine atherosclerosis.

BACKGROUND: Detection of inflamed atherosclerotic plaques is of crucial importance. The carotid artery cuff-model in ApoE(-/-) mice results in shear-stress induced atherosclerosis with inflamed plaques upstream (US) and 'stable' plaques downstream (DS) of the cuff. We evaluated the potential of F-18-FDG PET/CT to differentiate these plaque phenotypes. METHODS: A predefined cuff was implanted round the left (n = 23) or right (n = 12) common carotid artery (CCA) of 35 ApoE(-/-) mice on a cholesterol-rich diet. Small animal F-18-FDG PET/CT was performed after 4, 6 and 8 weeks. F-18-FDG uptake was quantified US and DS of the cuff and on the contralateral CCA. Subsequently, regional F-18-FDG uptake was normalized by the contralateral CCA uptake to obtain plaque-to-background (P/B)-ratios. Thereafter, CCA were explanted and investigated by immunohistology. RESULTS: P/B-ratio in the US-plaques increased from 1.22 ± 0.23 at 4 weeks over 1.23 ± 0.32 at 6 weeks to 1.37 ± 0.56 (p = ns) at 8 weeks after cuff implantation (left and right side of cuff implantation considered together). Uptake in the DS-plaques remained stable (1.14 ± 0.23, 1.10 ± 0.26 and 1.11 ± 0.25; p = ns). Uptake in the US-plaques was significantly higher than in the DS-plaques (all p < 0.05). P/B-ratios correlated with plaque size, degree of stenosis and macrophage density in the plaques. Moreover, there was a correlation between plaque size and macrophage density in the plaque. CONCLUSIONS: F-18-FDG-PET/CT distinguishes atherosclerotic plaques with an inflamed from those with a 'stable' phenotype in a mouse model of shear-stress induced atherosclerosis in vivo.

Variability of Proliferation and Diffusion in Different Lung Cancer Models as Measured by 3'-Deoxy-3'-¹8F-Fluorothymidine PET and Diffusion-Weighted MR Imaging.

UNLABELLED: Molecular imaging allows the noninvasive assessment of cancer progression and response to therapy. The aim of this study was to investigate molecular and cellular determinants of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET and diffusion-weighted (DW) MR imaging in lung carcinoma xenografts. METHODS: Four lung cancer cell lines (A549, HTB56, EBC1, and H1975) were subcutaneously implanted in nude mice, and growth was followed by caliper measurements. Glucose uptake and tumor proliferation were determined by (18)F-FDG and (18)F-FLT PET, respectively. T2-weighted MR imaging was performed, and the apparent diffusion coefficient (ADC) was determined by DW MR imaging as an indicator of cell death. Imaging findings were correlated to histology with markers for tumor proliferation (Ki67, 5-bromo-2'-deoxyuridine [BrdU]) and cell death (caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). The expression of human equilibrative nucleoside transporter 1 (hENT1), thymidine kinase 1 (TK1), thymidylate synthase, and thymidine phosphorylase (TP) were analyzed by Western blot and immunohistochemistry. Thymidine levels were determined by liquid chromatography-mass spectrometry. RESULTS: Xenografts varied with respect to in vivo growth rates. MR imaging and PET revealed intratumoral heterogeneities, which were confirmed by histology. (18)F-FLT uptake differed significantly between tumor lines, with A549 and H1975 demonstrating the highest radiotracer accumulation (A549, 8.5 ± 3.2; HTB56, 4.4 ± 0.7; EBC1, 4.4 ± 1.2; and H1975, 12.1 ± 3.5 maximal percentage injected dose per milliliter). In contrast, differences in (18)F-FDG uptake were only marginal. No clear relationship between (18)F-FLT accumulation and immunohistochemical markers for tumor proliferation (Ki67, BrdU) as well as hENT1, TK1, or TS expression was detected. However, TP was highly expressed in A549 and H1975 xenografts, which was accompanied by low tumor thymidine concentrations, suggesting that tumor thymidine levels influence (18)F-FLT uptake in the tumor models investigated. MR imaging revealed higher ADC values within proliferative regions of H1975 and A549 tumors than in HTB56 and EBC1. These ADC values were negatively correlated with cell density but not directly related to cell death. CONCLUSION: A direct relationship of (18)F-FLT with proliferation or ADC with cell death might be complicated by the interplay of multiple processes at the cellular and physiologic levels in untreated tumors. This issue must be considered when using these imaging modalities in preclinical or clinical settings.

No significant difference in the prognostic value of the 5th and 7th editions of AJCC staging for differentiated thyroid cancer.

OBJECTIVE: The seventh edition of the American Joint Committee on Cancer (AJCC) has more detailed staging categories for differentiated thyroid cancer (DTC) than the fifth edition. The aim was to compare potential alterations in the disease-specific (DSS), event-free (EFS) and overall survival (OS), after reclassification from the fifth to the seventh edition. METHODS: Data of 2460 patients with DTC referred to our centre were reclassified from the fifth to the seventh edition of AJCC. DSS, EFS and OS were calculated using the Kaplan-Meier method and compared by the log-rank test. The relative abilities of each edition to predict survival were calculated by the proportion of variance explained (PVE). RESULTS: After reclassification to the seventh edition, there was an increase in stage I and IV patients from 58·1% to 65·0% and from 6·2% to 10·1%, respectively, and a corresponding decrease in stage II and III patients from 22·4% to 12·5% and 13·3% to 12·4%, respectively. As to DSS, the seventh edition had only a marginally higher PVE value than the fifth edition. With respect to EFS, the predictability of the seventh edition was even inferior to that of the fifth edition. Similarly, with regard to OS, the PVE value was slightly better for the older edition. Furthermore, a comparison only for those patients affected by the reclassification revealed no differences for DSS, EFS or OS between classifications. CONCLUSION: When comparing the stages of the seventh with the fifth edition of the AJCC for DTC, there was no significant difference in predicting DSS, EFS and OS.

Pulmonary vein isolation in patients with paroxysmal atrial fibrillation is associated with regional cardiac sympathetic denervation.

BACKGROUND: Circumferential pulmonary vein isolation (PVI) is the cornerstone of the current state-of-the-art management of atrial fibrillation (AF). However, the precise mechanisms behind AF relapses post PVI are still unknown. Since the activity of the autonomous nervous system is crucial in triggering paroxysmal AF, we hypothesized that PVI is associated with changes of cardiac sympathetic activity. METHODS: Sixteen patients with paroxysmal AF underwent cardiac iodine-123-meta-iodobenzylguanidine (123I-mIBG) planar cardiac imaging and single-photon emission computed tomography with low-dose computed tomography (SPECT/CT) for attenuation correction before and 4 weeks after PVI. The heart-to-mediastinum ratio (H/M ratio), washout rate (WR), regional myocardial uptake, and regional washout were analyzed. RESULTS: The late H/M ratio was unchanged by PVI (pre, 2.9 ± 0.5 vs. post, 2.7 ± 0.6, p = 0.53). Four of the 16 patients (25%) displayed regional deficits before PVI. After PVI, regional deficits were present in ten patients (62.5%) with newly emerging deficits localized in the inferolateral wall. In a 6-month follow-up, four out of the ten patients (40%) with regional 123I-mIBG defects suffered from a recurrence of AF, while only one of the six patients (16.7%) without a regional 123I-mIBG defect experienced a recurrence. CONCLUSION: A significant number of patients with paroxysmal AF show regional cardiac sympathetic innervation deficits at baseline. In addition, PVI is associated with newly emerging defects. The presence of regional sympathetic denervation after PVI may correlate with the risk of AF relapses.

Synthesis and in vivo evaluation of an (18)F-labeled glycoconjugate of PD156707 for imaging ETA receptor expression in thyroid carcinoma by positron emission tomography.

Disturbances of the endothelin axis have been described in tumor angiogenesis and in highly vascularized tumors, such as thyroid carcinoma. Consequently, the endothelin (ET) receptor offers a molecular target for the visualization of the endothelin system in vivo by positron emission tomography (PET). We therefore endeavoured to develop a subtype-selective ETA receptor (ETAR) radioligand by introduction of a glycosyl moiety as a hydrophilic building block into the lead compound PD156707. Employing click chemistry we synthesized the triazolyl conjugated fluoroglucosyl derivative 1 that had high selectivity for ETAR (4.5 nM) over ETBR (1.2 µM). The radiosynthesis of the glycoconjugate [(18)F]1 was achieved by concomitant (18)F-labeling and glycosylation, providing [(18)F]1 in high radiochemical yields (20-25%, not corrected for decay, 70 min) and a specific activity of 41-138 GBq/µmol. Binding properties of [(18)F]1 were evaluated in vitro, and its biodistribution was measured in K1 thyroid carcinoma xenograft nude mice ex vivo and by molecular imaging. Although the very substantial excretion via hepatobiliary clearance was not decisively influenced by glycosylation, the (18)F-glycoconjugate was more stable in blood during PET recordings than was the previously described (18)F-fluoroethoxy analog. Small-animal PET imaging showed displacable binding of [(18)F]1 at ETAR in K1 tumors. The simple and efficient (18)F-radiosynthesis together with the excellent stability make the (18)F-labeled glycoconjugate [(18)F]1 a promising molecular tool for preclinical PET imaging studies of ETAR expression in thyroid carcinoma and other conditions with marked angiogenesis.

Inverse 1,2,3-triazole-1-yl-ethyl substituted hydroxamates as highly potent matrix metalloproteinase inhibitors: (radio)synthesis, in vitro and first in vivo evaluation.

Noninvasive imaging and quantification of matrix metalloproteinase (MMP) activity in vivo are of great (pre)clinical interest. This can potentially be realized by using radiolabeled MMP inhibitors (MMPIs) as positron emission tomography (PET) imaging agents. Triazole-substituted MMPIs, discovered by our group, are highly potent inhibitors of MMP-2, -8, -9, and -13. The triazole ring and its position contribute significantly to the potency of the MMP inhibitor. To evaluate structure-activity relationships (SARs) of the initially discovered triazole-substituted MMPIs, an additional CH2-group between the backbone of the molecule and the triazole core was inserted, and the triazole ring was "inversed" by switching the alkyne and azide groups. Similar to the original triazole-substituted hydroxamates, the inverse triazole MMPIs are excellent inhibitors with promising in vivo properties. Pharmacokinetic properties and metabolic stability of an (18)F-labeled candidate in mice were investigated.

A closer look at the bromine-lithium exchange with tert-butyllithium in an aryl sulfonamide synthesis.

A practical protocol for the one-pot synthesis of various aryl sulfonamides, notably of pyridine-core-substituted 7-azaindolyl sulfonamides, is described. A key step is the well-known bromine-lithium exchange reaction of an aryl bromide with tert-butyllithium (t-BuLi). Differing from the common practice to use 2 or more equiv of organolithium, the exact amount of t-BuLi needed for a sufficient exchange reaction is determined for each aryl bromide in a GC-MS-assisted experiment.

Cerebellar anaplastic astrocytoma in an adult with neurofibromatosis type 1: case report and review of literature.

BACKGROUND: Low-grade gliomas (e.g., pilocytic astrocytomas) are frequently found in patients with neurofibromatosis type 1 (NF1). Whereas most of those lesions are located supratentorially, cerebellar manifestations are described in < 1%. Malignant variants like glioblastoma and anaplastic astrocytoma (AA) are only rarely observed in NF1 patients. Thus, cerebellar AA is very infrequent and has not yet been described in an adult NF1 patient. CLINICAL PRESENTATION: We present the case of a 54-year-old male patient with von Recklinghausen disease who had a diffuse contrast-enhancing cerebellar mass that was resected guided by aminolevulinic acid (ALA)-fluorescence. Histopathological analyses revealed an AA with lack of pilocytic features or O6-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation. Due to the proximity of the tumor to the brainstem, adjuvant temozolomide chemotherapy was administered rather than first-line radiotherapy. Although the patient recovered quickly after the operation and tumor progression was ruled out in follow-up magnetic resonance imaging (MRI), the patient strongly deteriorated during a 16-month follow-up, and MRI revealed severe leukoencephalopathy. Extensive electrophysiological and radiological examination revealed a neurodegenerative disease of unknown etiology. Finally, the patient's condition improved receiving levodopa. CONCLUSIONS: A literature search yielded only one previously published case of an AA in a 9-year-old girl with NF1. Tumor control after resection was achieved in both patients; however, the patient in the mentioned report received radiation instead of temozolomide. In spite of different adjuvant therapies, tumor control for at least 16 months was achieved in both published cases. Thus, even though the role of adjuvant treatment options remains to be further elucidated, surgery is the appropriate therapy in these uncommon tumors providing mass reduction and histological diagnosis as well as tumor control.

PET with 18F-FDG-labeled T lymphocytes for diagnosis of acute rat renal allograft rejection.

UNLABELLED: We proposed small-animal PET with (18)F-FDG-labeled T lymphocytes as a new method for image-based diagnosis of acute allogeneic renal transplant rejection (AR) established in a rat model. METHODS: One and 2 h after tail vein injection of 30 × 10(6) ex vivo (18)F-FDG-labeled human T cells into male 10-wk-old uninephrectomized, allogeneically transplanted rats (aTX; Lewis-brown Norway [LBN] to Lewis), whole-body radioactivity distribution was assessed in vivo by small-animal PET (postoperative day 4), and percentage injected dose (%ID) as a parameter of T-cell infiltration was assessed and compared between graft and native kidney. In vivo results were confirmed by autoradiography and staining of human CD3 after postmortem dissection. Syngeneically transplanted rats (sTX) (LBN to LBN), rats with ischemia-reperfusion injury (IRI) (45-min warm ischemia), and rats subjected to acute cyclosporine A (CSA) toxicity (50 mg/kg for 2 d intraperitoneally) served as controls. RESULTS: The accumulation of labeled cells was significantly elevated in allografts with AR (1.07 ± 0.28 %ID), compared with native control kidneys (0.49 ± 0.18 %ID) (P < 0.0001). No differences were found among native controls, sTX, CSA toxicity, and kidneys with IRI. In vivo uptake of (18)F-FDG cells measured in the PET scanner correlated with results obtained by autoradiography, histologic evaluation, and polymerase chain reaction. CONCLUSION: We proposed graft PET imaging using (18)F-FDG-labeled T cells as a new option to detect rat renal AR with a low dose of (18)F-FDG in a noninvasive, fast, and specific manner in rats.