Bone block augmentation from the iliac crest for treatment of deep osteochondral defects of the knee resembles biomechanical properties of the subchondral bone.

PURPOSE: Bone block augmentation from the iliac crest can be used for reconstruction of the osteochondral unit to restore the underlying subchondral bone upon restoration of the cartilaginous layer via matrix-induced chondrocyte transplantation. To critically understand the successful restoration of the defect, biomechanical and histological analysis of the implanted bone blocks is required. The aim of the study was to analyse the ability of the bone block technique to restore huge bone defects by mimicking the physiological subchondral zone. METHODS: The experiments were performed using lateral femoral condyles and iliac crest bone grafts from the same cadavers (n = 6) preserved using the Thiel method. CT scans were made to evaluate bone pathology. Bone mineral density of all specimens was evaluated in the femoral head prior to testing. A series of tests were conducted for each pair of specimens. A static compression test was performed using an electro dynamic testing machine with maximal strength and failure behavior analyzed. Biomechanical tests were performed in the medial-lateral direction for iliac crest and for femoral condyles with and without removal of the cartilage layer. Histological analysis was performed on decalcified specimens for comparison of the condyle at lesion site and the graft. RESULTS: No significant difference in failure load could be found for iliac crest (53.3-180.5 N) and femoral condyle samples upon cartilage removal (38.5-175.1 N) (n.s.). The femoral condyles with an intact cartilage layer showed significantly higher loads (118.3-260.4N) compared to the other groups indicating that native or regenerated cartilage can further increase the failure load (p < 0.05). Bone mineral density significantly influenced failure load in all study groups (p < 0.05). Histological similarity of the cancellous bone in the femoral condyle and in the iliac crest was observed. However, within the subchondral zone, there was a higher density of sponge like organized trabeculae in the bone samples from the iliac crest. Tide mark was only detected at the osteochondral interface in femoral condyles. CONCLUSION: This study demonstrated that, bone blocks derived from the iliac crest allow a biomechanical appropriate and stable restoration of huge bony defects by resembling the subchondral zone of the femoral condyle. Therefore, bone augmentation from the iliac crest combined with matrix-induced autologous chondrocyte transplantation seems to be a reasonable method to treat these challenging injuries.

Dual-energy computed tomography after endovascular aortic aneurysm repair: the role of hard plaque imaging for endoleak detection.

OBJECTIVES: To assess the diagnostic accuracy of dual-energy computed tomography (DECT) for detection of endoleaks and aneurysm sac calcifications after endovascular aneurysm repair (EVAR) using hard plaque imaging algorithms. MATERIALS AND METHODS: One hundred five patients received 108 triple-phase contrast-enhanced CT (non-contrast, arterial and delayed phase) after EVAR. The delayed phase was acquired in dual-energy and post-processed using the standard (HPI-S) and a modified (HPI-M) hard plaque imaging algorithm. The reference standard was determined using the triple-phase CT and contrast-enhanced ultrasound. All images were analysed separately for the presence of endoleaks and calcifications by two independent readers; sensitivity, specificity and interobserver agreement were calculated. RESULTS: Endoleaks and calcifications were present in 25.9 % (28/108) and 20.4 % (22/108) of images. The HPI-S images had a sensitivity/specificity of 54 %/100 % (reader 1) and 57 %/99 % (reader 2), the HPI-M images of 93 %/92 % (reader 1) and 96 %/92 % (reader 2) for detection of endoleaks. For detection of calcifications HPI-S had a sensitivity/specificity of 91 %/99 % (reader 1) and 95 %/97 % (reader 2), the HPI-M images of 91 %/99 % (reader 1) and 91 %/99 % (reader 2), respectively. CONCLUSION: Using HPI-M, DECT enables an accurate diagnosis of endoleaks after EVAR and allows distinguishing between endoleaks and calcifications with high diagnostic accuracy. KEY POINTS: • Dual-energy computed tomography allows the diagnosis of aortic pathologies after EVAR. • Hard plaque imaging algorithms can distinguish between endoleaks and aneurysm sac calcifications. • The modified hard plaque imaging algorithm detects endoleaks with high diagnostic accuracy.

Diagnosis of pericardial effusion with a new generation hand-carried ultrasound device in cardiothoracic intensive care unit patients.

BACKGROUND: Technological advances introduced hand-carried ultrasound (HCU) imagers in daily clinical workflow providing several benefits such as fast bedside availability and prompt diagnosis. PURPOSE: To evaluate the diagnostic yield of a latest generation HCU imager compared to contrast-enhanced multidetector computed tomography (MDCT) for the detection of pericardial effusion (PE) in cardiothoracic intensive care unit (ICU) patients. MATERIAL AND METHODS: Thirty-six patients from a cardiothoracic ICU were enrolled to this study irrespective of their underlying disease. All patients were examined with a new generation HCU for the presence of PE. Definite diagnosis of PE was based on findings of MDCT as standard of reference. Statistical analysis was performed using PASW 18. RESULTS: PE was identified in 20 patients by MDCT (prevalence 56%). The HCU examination was carried out technically successfully in all patients. Sensitivity, specificity, positive and negative predictive value of HCU for the diagnosis of PE were 75%, 88%, 88%, and 74%, respectively. CONCLUSION: HCU provides rapid, practical, reliable, and cost-effective diagnosis of PE in patients on cardiothoracic ICU.

Bedside diagnosis of pleural effusion with a latest generation hand-carried ultrasound device in intensive care patients.

BACKGROUND: Further development established hand-carried ultrasound (HCU) imagers in daily clinical workflow providing several advantages such as fast bedside availability and prompt diagnosis. PURPOSE: To evaluate the diagnostic yield of a latest generation HCU imager compared to chest radiography (CR) for the detection of pleural effusion (PE) in intensive care patients. MATERIAL AND METHODS: Forty-eight hemithoraces of 24 patients on surgical intensive care units were enrolled in this study. All hemithoraces were evaluated using both HCU and CR. Definite diagnosis of PE was achieved using a high-end ultrasound system as standard of reference. Statistical analysis was performed using 2 × 2 tables and a McNemar test. A P value of <0.05 was considered statistically significant. RESULTS: PE was present in 35 of 48 hemithoraces (73%). The HCU examination was carried out technically successfully in all hemithoraces. Sensitivity and specificity of HCU for the diagnosis of PE was 91% and 100%, respectively, whereas sensitivity and specificity of CR was 74% and 31%, respectively. The difference between HCU and CR was statistically significant with respect to specificity but not sensitivity (P = 0.008 and P = 0.11, respectively). CONCLUSION: Due to its ease of use and its high diagnostic yield HCU systems of the latest generation constitute a helpful technique for the primary assessment of PE.

[Superior vena cava occlusion : Radiological placement of a central venous port system via femoral vein access]. / Okklusion der V. cava superior : Radiologische Implantation eines zentralvenösen Portsystems über einen femoralen Zugang.

We report on a young patient with cancer of unknown primary origin with occlusion of the superior vena cava due to mediastinal lymphadenopathy. In order to continue infusion of palliative chemotherapy a central venous port system was radiologically implanted via a right femoral vein access. The port reservoir was placed craniomedial to the right anterior superior iliac spine. This approach was considered convenient in respect to comfort in wearing trousers. In addition, at this site the port reservoir is easily accessible for medical staff. It was possible to draw blood via the port system and to infuse the chemotherapy without complications. The present case shows that in cases of occlusion of the superior vena cava radiological implantation of a central venous port system via a femoral vein access is a useful option.

Simple diameter measurement as predictor of liver volume and liver parenchymal disease.

To investigate the accuracy of liver diameters for estimation of liver size and to evaluate their application as tool for assessment of parenchymal liver disease. In the course of a population-based study, (SHIP) one thousand nine hundred thirty-nine volunteers underwent magnetic resonance imaging (MRI) of the liver including 3D gradient echo MRI sequences. Maximum liver diameters were measured in cranio-caudal (CC), anterior-posterior (AP), medial-lateral (ML) orientation. Diameters were compared with true liver volume assessed by liver segmentation. Additionally, age-dependent reference values for diameters were defined. Finally, accuracy of liver diameters was assessed to discriminate volunteers with healthy livers and participants with parenchymal changes, measured by MRI and laboratory. Reference values of liver diameters within the healthy population (n = 886) were defined as follows (mean ± standard deviation, confidence interval CI in cm): CC 17.2 ± 2, CI 13.6/21.2; AP 15.8 ± 1.9, CI 12.6/19.8; ML 19.7 ± 2.3, CI 15.8/24.6. There was a poor correlation using linear regression between liver diameter and true liver volume; CC 0.393, AP 0.359; ML 0.137. The AP direction shows the best correlation to discriminate between healthy and pathologic liver changes; AUC 0.78; p < 0.001, CC AUC 0.53; p < 0.001 and ML AUC 0.52; p = 0.008. Measurement of liver diameter, especially in the anterior-posterior direction is a simple option to detect chronic liver disease but less suitable for prediction of liver volume.

Reliability and accuracy of straightforward measurements for liver volume determination in ultrasound and computed tomography compared to real volumetry.

To evaluate the suitability of volume index measurement (VI) by either ultrasound (US) or computed tomography (CT) for the assessment of liver volume. Fifty-nine patients, 21 women, with a mean age of 66.8 ± 12.6 years underwent US of the liver followed immediately by abdominal CT. In US and CT imaging dorsoventral, mediolateral and craniocaudal liver diameters in their maximum extensions were assessed by two observers. VI was calculated by multiplication of the diameters divided by a constant (3.6). The liver volume determined by a manual segmentation in CT ("true liver volume") served as gold standard. True liver volume and calculated VI determined by US and CT were compared using Bland-Altman analysis. Mean differences of VI between observers were - 34.7% (- 90.1%; 20.7%) for the US-based and 1.1% (- 16.1%; 18.2%) for the CT-based technique, respectively. Liver volumes determined by semi-automated segmentation, US-based VI and CT-based VI, were as follows: 1.500 ± 347cm3; 863 ± 371cm3; 1.509 ± 432cm3. Results showed a great discrepancy between US-based VI and true liver volume with a mean bias of 58.3 ± 66.9%, and high agreement between CT-based VI and true liver volume with a low mean difference of 4.4 ± 28.3%. Volume index based on CT diameters is a reliable, fast and simple approach for estimating liver volume and can therefore be recommended for clinical practice. The usage of US-based volume index for assessment of liver volume should not be used due to its low accuracy of US in measurement of liver diameters.

Severe acute pancreatitis requiring drainage therapy: findings on computed tomography as predictor of patient outcome.

BACKGROUND/AIMS: To evaluate whether morphologic features on computed tomography (CT) correlate with outcome of patients with severe acute pancreatitis (SAP). METHODS: 80 patients with SAP requiring percutaneous drainage therapy were retrospectively analyzed. Twelve CT features beyond the CT severity index (CTSI) were studied. Endpoints for patient outcome were patient death, length of hospital and ICU stay. The twelve features and the CTSI score were correlated with mortality using Kaplan-Meier estimator and correlated with length of hospital and ICU stay using the χ(2) test. A p value ≤0.05 was considered statistically significant. RESULTS: Two CT features exhibited a significant correlation with mortality: (1) the number of parts of pancreas (head, corpus, tail) that exhibited areas of necrosis and (2) the presence of distant fluid collections (posterior pararenal space and/or paracolic gutter). Mortality was 42% (21 of 50 patients) and 20% (6 of 30 patients) if two/all three parts or none/one part of the pancreas exhibited necrosis, respectively. Mortality was 46% (18 of 39 patients) and 22% (9 of 41 patients) if distant fluid collections were present or absent, respectively. All other imaging features including the CTSI showed no significant correlation with patient outcome. CONCLUSION: We identified two morphologic features on CT that might be helpful to predict prognosis of patients suffering from SAP. and IAP.

Detection and characterization of endoleaks following endovascular treatment of abdominal aortic aneurysms using contrast harmonic imaging (CHI) with quantitative perfusion analysis (TIC) compared to CT angiography (CTA).

PURPOSE: To show the feasibility of the detection of endoleaks following endovascular treatment of aortic aneurysms using contrast harmonic imaging (CHI) in comparison to computed tomography angiography (CTA). MATERIALS AND METHODS: 51 patients with suspected endoleaks, who underwent previous endovascular treatment for abdominal aortic aneurysm, were examined using CTA and vascular ultrasound. Biphasic CTA in all cases and digital subtraction angiography (DSA) in 8 patients were evaluated by two radiologists in consensus and served as the standard of reference. Ultrasound was performed by an experienced examiner with a multi-frequency linear transducer (2 - 4 MHz) using CHI following bolus injection of 2.4 ml of SonoVue® IV (maximum 5 ml). All images were evaluated by two observers in consensus regarding the reperfusion of the abdominal aneurysm using time intensity curve (TIC) analysis. RESULTS: In 30 of 51 patients, endoleaks were detected concordantly in CHI and CTA. In 20 of 51 patients, no endoleak was found in CHI and CTA/DSA. In one patient, a type II endoleak could initially only be detected in CHI and was later confirmed in follow-up examinations by CTA (sens. 99%, spec. 93%, NPV 99 %, PPV 95%). TIC analysis allowed evaluation of the perfusion dynamics of endoleaks in all patients. Significant differences were found (p < 0.05, Mann Whitney U Test) regarding the perfusion within the aneurysm when an endoleak was present (10.39 ± 4.29 dB) or not present (6.42 ± 2.86 dB). CONCLUSION: CHI with perfusion analysis allows definite detection of endoleaks, especially if contraindications for CTA are present. CHI presents an alternative for follow-up monitoring.

[A 47-year-old patient with longstanding nicotine abuse, increasing dyspnea on exertion and lower and peripheral lung predominant ground-glass opacities]. / 47-jähriger Patient mit langjährigem Nikotinabusus, zunehmender Belastungsdyspnoe und diffusen, peripher und basal betonten Milchglastrübungen in der Lunge.

The causal relationship between cigarette smoking and a number of interstitial lung diseases continues to evolve. These "smoking-related interstitial lung diseases" (SR-ILD) are a heterogeneous group of entities which have overlapping imaging findings and which can coexist. The presented case of a patient with smoking history and pulmonary ground-glass opacities demonstrates that thorough knowledge of the various manifestations of SR-ILD is essential for a confident diagnosis.

[A 74-year-old female patient with histologically proven carcinoid of the lungs and pulmonary mosaic pattern]. / 74-jährige Patientin mit histologisch gesichertem Karzinoid der Lunge und pulmonalem Mosaikmuster.

Diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) can be idiopathic or reactive to chronic airway disease, then termed pulmonary neuroendocrine cell hyperplasia (PNECH). DIPNECH can be complicated by obliterative bronchiolitis and is presumably often misdiagnosed because the clinical symptoms are unspecific, the entity is relatively unknown and high-resolution computed tomography (HRCT) in inspiration and expiration is necessary for the diagnosis. However, the HRCT findings of air-trapping in combination with nodules are very characteristic and should raise suspicion of this entity. DIPNECH is thought to be a precursor of tumorlets and carcinoids and usually runs a benign course. The diagnosis is confirmed by histology.

[Stenting in the treatment of chronic mesenteric ischemia: technical and clinical success rates]. / Chronische mesenteriale Ischämie: Technische und klinische Erfolgsrate der perkutanen Stentangioplastie.

PURPOSE: To evaluate the technical and clinical success rates of percutaneous stent revascularization in the treatment of chronic mesenteric ischemia (CMI). PATIENTS AND METHODS: 17 patients (12 female) with typical symptoms of CMI were treated by percutaneous stent placement for stenoses of the splanchnic arteries (celiac trunk; superior mesenteric artery, SMA; inferior mesenteric artery, IMA). The primary and secondary technical success, primary and secondary clinical success, and the long-term clinical outcome were determined. RESULTS: A total of 24 stents were implanted in 21 splanchnic arteries (12 stents in the celiac trunk, 11 in the SMA and 1 in the IMA). The primary technical success rate was 91% (19/21 arteries), the secondary technical success rate was 95% (21/22 arteries). Clinical follow-up was available for 16 patients. The primary clinical success rate was 81% (13/16 patients). Following two secondary interventions, the secondary clinical success rate was 94% (15/16 patients). Long-term clinical success was achieved in 15 of 16 patients (94%) with a mean follow-up of 26 months. One patient died within 30 days of the intervention and two patients demonstrated major complications (1 dissection, 1 stent dislocation). None of the patients required surgical revascularization and none of the patients died due to recurrent mesenteric ischemia. CONCLUSION: Percutaneous stent placement for the treatment of CMI can be performed with a high technical and clinical success rate as well as an excellent long-term clinical outcome.

Reference values of liver volume in Caucasian population and factors influencing liver size.

PURPOSE: To investigate factors influencing liver size and to determine reference values of liver volume (LV) for healthy subjects. METHODS: 2773 volunteers underwent magnetic resonance imaging (MRI) of the liver in the setting of the population based Study of Health in Pomerania. Based on measurement of maximum diameters in three orientations, LVs were calculated and correlated with demographic factors such as age, gender, and body mass index. In addition, LVs of healthy volunteers and participants with parenchymal liver diseases such as fatty liver disease, iron overload, fibrosis/cirrhosis were compared. Adjusted reference values of liver volumes were defined for the group of healthy participants. RESULTS: In general, mean LV (mean ±â€¯standard deviation) was 1505 ±â€¯385 cm3. Age, gender and body mass index correlated significantly with the liver volume (p ≤ 0.001). Parenchymal liver diseases significantly influence LV (with: 1624 ±â€¯420 cm3, n = 1525 and without parenchymal liver diseases: 1360 ±â€¯273 cm3; n = 1.248, p ≤ 0.001). Compared to LV of participants without liver diseases, LV was increased in volunteers with hepatic steatosis (1717 ±â€¯419 cm3; n = 1111), liver iron overload (1558 ±â€¯367 cm3; n = 553; p ≤ 0.001) as well as in participants with fibrosis/cirrhosis (1494 ±â€¯459 cm3; n = 383). CONCLUSIONS: LV is influenced by age, body mass index and parenchymal liver diseases. Reference values were established to aid in the diagnosis of parenchymal liver diseases.

Accuracy of simple approaches to assessing liver volume in radiological imaging.

OBJECTIVES: The purpose of the study was to evaluate the accuracy of measured diameters and calculated volume indices for determining liver size and to derive a simple approach for estimating liver volume. METHODS: Three hundred twenty-nine volunteers (cohort A) were grouped according to liver volume: small (n = 109), medium (n = 110), and large (n = 110). True liver volume was determined by magnetic resonance imaging (MRI) using manual segmentation. Maximum diameters (maxdiam) of the liver and distances in midclavicular line (MCL) were measured. Volume indices were calculated as a simple product of the measured diameters. The calculated volume indices were calibrated to predict true liver volume. Performance of the calibrated method was evaluated in a control group (cohort B) including randomly selected volunteers (n = 110) and a patient group with histopathologically proven parenchymal liver diseases (n = 28). RESULTS: In cohort A, there was strong correlation between diameters and true liver volume (r s = 0.631-0.823). Calculated volume indices had slightly better correlation (maxdiam r s = 0.903, MCL r s = 0.920). A calibration index was calculated from the volumes and diameters determined in cohort A. Application of this calibration on cohort B verified a very strong correlation between calibrated volume indices and true liver volume (maxdiam r s = 0.920, MCL r s = 0.909). In addition, the low mean difference between predicted liver volume (maxdiam = -70.9 cm(3);MCL = -88.4 cm(3)) and true liver volume confirms that the calibrated method allows accurate assessment of liver volume. CONCLUSIONS: Both simple diameters and volume indices allow estimating liver size. A simple calibration formula enables prediction of true liver volume without significant expense.

Urokinase induces proliferation of human ovarian cancer cells: characterization of structural elements required for growth factor function.

Ovarian cancer metastasis is associated with an increase in the urokinase-type plasminogen activator (uPA) and its receptor uPAR. We present evidence that binding of uPA to uPAR provokes a mitogenic response in the human ovarian cancer cell line OV-MZ-6 in which endogenous uPA production had been significantly reduced by stable uPA 'antisense' transfection. High molecular weight (HMW) uPA, independent of its enzymatic activity, produced an up to 95% increase in cell number concomitant with 2-fold elevated [3H]thymidine incorporation as did the catalytically inactive but uPAR binding amino-terminal fragment of uPA, ATF. uPA-induced cell proliferation was significantly decreased by blocking uPA/uPAR interaction by the monoclonal antibody IIIF10 and by soluble uPAR. The efficiency of the uPAR binding synthetic peptide cyclo19,31 uPA19-31 to enhance OV-MZ-6 cell growth proved this molecular domain to be the minimal structural determinant for uPA mitogenic activity. Dependence of uPA-provoked cell proliferation on uPAR was further demonstrated in Raji cells which do not express uPAR and were thus not induced by uPA. However, upon transfection with full-length uPAR, Raji cells acquired a significant growth response to HMW uPA and ATF.

Tumor cell spheroids as a model for evaluation of metabolic changes after irradiation.

UNLABELLED: Tumor cell spheroids provide a good model to evaluate the relationship between tumor volume and the number of viable cells in the volume with the uptake of metabolic tracers before and after therapy. They represent the only in vitro model that allows the determination of the activity per unit volume, a parameter which is relevant for interpretation of PET studies. The purpose of this study was to evaluate this model with respect to the uptake of 14C-FDG, 3H-methionine and 3H-thymidine with and without exposure to irradiation. METHODS: Spheroids of the human adenocarcinoma cell line SW 707 were incubated in media containing 14C-FDG, 3H-methionine or 3H-thymidine for 1 hr at 1, 4, 8, 24 and 48 hr after exposure to a single radiation dose of 6 Gy together with control spheroids. Tracer uptake after incubation was expressed in cpm/ spheroid, cpm/1000 viable cells and cpm/0.01 mm3. In addition, the proliferative capacity of control and irradiated spheroids was determined using the clonogenic assay. RESULTS: Spheroid uptake of FDG decreased with time after irradiation, while the uptake per 1000 viable cells was increased significantly. The activity per unit volume remained unchanged in comparison to control spheroids. Methionine uptake per spheroid was unchanged after irradiation because of the high increase in uptake per 1000 viable cells. Uptake per unit volume also remained unchanged in comparison to controls. Thymidine uptake per 1000 viable cells did not change after irradiation but showed significant differences in uptake per spheroid and per unit volume compared to controls. The percentage of thymidine incorporated into the TCA-precipitable fraction containing DNA was 50% in controls and decreased to 12% at 24 hr after irradiation. The suppressed clonogenic capacity early after therapy recovered with the increase in thymidine uptake and with the increase in thymidine incorporation into DNA. CONCLUSION: The results show that the activity determined within a certain tumor volume is a balance between the increased tracer uptake by surviving cells after therapy and the lack of tracer uptake by dead cells, which still contribute to the tumor volume. Thus, the resulting unchanged activity per unit volume within the spheroid, as found for FDG and methionine, may not fully reflect therapy-induced metabolic changes in tumors.

Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo.

UNLABELLED: The aim of the study was to investigate the transport mechanism and uptake kinetics of the new 18F-labeled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (L-[18F]FET) and D-[18F]FET in human SW 707 colon carcinoma cells and the in vivo biodistribution of this tracer in SW 707 tumor-bearing mice. METHODS: SW 707 cells were incubated with L- and D-[18F]FET under physiologic amino acid concentrations with and without the competitive transport inhibitors 2-amino-2 norbornane-carboxylic acid and a-(methylamino)isobutyric acid plus serine. For the investigation of the transport capacity, unlabeled L-FET was added to the samples. In addition, xenotransplanted mice were injected intravenously with L-[18F]FET; killed 10, 30, 60 and 120 min after injection; and the radioactivity concentration in different organs was measured in a gamma counter. RESULTS: The in vitro kinetic experiments showed a fast initial uptake of L-[18F]FET into the cells up to 6 min, followed by a nearly constant tracer concentration. The accumulation factor, calculated as the ratio between intracellular and extracellular tracer concentration, ranged from 3.0 to 5.0. In comparison, D-[18F]FET did not accumulate in the cells. Washing the cells in medium at 37 degrees C, after a 30-min incubation with L-[F-18]FET, led to a rapid decrease of radioactivity, which demonstrates the bidirectional transport. In addition, experiments with increasing concentrations of unlabeled L-FET indicated a linear correlation between L-FET uptake rate and the extracellular concentration. Results of transport inhibition experiments with the specific competitive inhibitors demonstrated that the uptake of L-FET into SW 707 cells was caused mainly (>80%) by the transport system L. In the in vivo studies, the half-life (t1/2 beta) of L-[18F]FET in the plasma was determined to be 94 min and the uptake into the brain increased to 120 min with a brain-to-blood ratio of 0.86. The xenotransplanted tumor showed higher uptake of L-[18F]FET (>6 %ID/g) at 30 and 60 min than all other organs, except the pancreas. The tumor-to-blood ratio reached about 2 between 30 and 120 min. CONCLUSION: L-[18F]FET, which is transported by the specific amino acid transport system L, seems to be a potential amino acid tracer for tumor imaging and therapy monitoring with PET.

Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging.

UNLABELLED: The aim of the study was to develop a simple 18F-labeled amino acid as a PET tracer for cerebral and peripheral tumors. O-(2-[18F]fluoroethyl)-L-tyrosine (L-[18F]FET) was synthesized and biologically evaluated. Results of the first human PET study are reported. METHODS: No carrier added (n.c.a.) and D-[18F]FET were prepared by 18F-fluoroethylation of L- and D-tyrosine in a two-step procedure. Biodistribution studies were performed in mice. The metabolic fate of L-[18F]FET was investigated in plasma, brain, tumor and pancreatic tissue samples using chromatographic procedures. Tumor uptake studies were performed in mammary carcinoma-bearing mice and in mice with the colon carcinoma SW 707. In a human PET study, a 59-y-old man with a recurrent astrocytoma was imaged using n.c.a. L-[18F]FET. RESULTS: Synthesis of [18F]FET was accomplished in about 50 min with an overall radiochemical yield of 40%. The uptake of L-[18F]FET in the brain of mice reached a level >2% ID/g between 30 and 60 min postinjection. The brain uptake of the D-isomer was negligible, indicating blood-brain barrier penetration by a specific amino acid transport system. L-[18F]FET is not incorporated into proteins. High-performance liquid chromatography (HPLC) analysis of brain, pancreas and tumor homogenates as well as plasma samples of mice at 10, 40 or 60 min postinjection showed only unchanged L-[18F]FET. Activity uptake in the bone did not exceed 2% ID/g at 40 min postinjection. The brain uptake of L-[18F]FET in mice bearing mammary carcinomas and colon carcinomas reached 7.1%+/-1.2% ID/g and 6.4%+/-1.7% ID/g 1h postinjection, respectively. In the first human study, L-[18F]FET-PET allowed a clear delineation of a recurrent astrocytoma. Thirty-five minutes postinjection, the tumor-to-cortex ratio was >2.7. A tumor-to-blood ratio >1.5 was reached at 30 min postinjection and continued to increase. No significant activity accumulation was observed in peripheral organs after approximately 40 min postinjection. CONCLUSION: The high in vivo stability of L-[18F]FET, its fast brain and tumor uptake kinetics, its low accumulation in nontumor tissue and its ease of synthesis strongly support further evaluation of L-[18F]FET as an amino acid tracer for cerebral and peripheral tumors.

Distribution of disialoganglioside GD2-antigen and binding of anti-GD2 antibodies on spheroids of neuroblastoma cell line.

The ganglioside GD2 is highly expressed on human tumors of neuroectodermal origin. We investigated by scanning electron microscopy the ganglioside GD2 distribution on the surface of spheroids of the neuroblastoma cell line SK-N-LO. About 50% of cells showed GD2 on the plasma membrane and the distribution of GD2 on most of these cells was heterogeneous, with more GD2 at the contact sites of the cells. The binding kinetics of the chimeric anti-GD2 antibody ch14.18 labelled with I-125 on spheroids (average diameter: 450 microns) was determined by gamma counting. Over 4 hours the antibody concentration was raised substantially but up to 24 hours there was only a very slow further increase. A clustered pattern of bound chimeric anti-GD2 antibody ch14.18 was found on a cross-section of the spheroid by autoradiography.

Growth inhibition of human papillary thyroid carcinoma cells and multicellular spheroids by anti-EGF-receptor antibody.

EGF has been reported to stimulate thyroid cell proliferation. In the present study we investigated the effects of anti-EGF-R-antibody (Mab 4253 both as monolayers and spheroids of an oxyphilic, non iodine metabolizing, papillary thyroid carcinoma cell line (ONCO-DG-1) and roughly characterized their EGF-R. Scatchard analysis with I-125-labeled-EGF demonstrated a low number of 1.5 x 10(4) EGF-R per monolayer cell (KD 4.1 X 10(-10) M) and only 6 x 10(3) EGF-R per spheroids cell (KD 5.0 X 10(-10) M). Already 80% of the binding sites were blocked by only 0.44 microgram/ml Mab 425. Proliferathe activity and EGF-R were found to be regularly distributed throughout the spheroids. Adding Mab 425 to medium containing 1 ng/ml EGF, inhibited the growth of monolayer cells by 15% (1 ng/ml Mab 425) and 28% (10 ngiml Mab 425), measured by the MTT-test. The volume growth of spheroids was inhibited by 10-15% using 2 micrograms/ml Mab 425, whereas their viability (MTT-Test) was almost identical. The results show that the anti-EGF-R-antibody (Mab 425) alone is not effective enough for therapeutical use, but it could be of clinical value in conjugation with radionuclides (e.g. I-131) in order to reach metastases not metabolizing iodine.