PET with O-(2-18F-Fluoroethyl)-L-Tyrosine in peripheral tumors: first clinical results.

O-(2-18F-Fluoroethyl)-L-Tyrosine (18F-FET) PET has shown promising results in brain tumor diagnosis. The aim of this prospective study was to evaluate 18F-FET PET in comparison with 18F-FDG PET in patients with peripheral tumors. METHODS: Forty-four consecutive patients with suspected malignant tumors underwent 18F-FET PET and 18F-FDG PET within 7 d. Whole-body PET studies were performed 1 h after intravenous injection of 370 MBq of 18F-FET or 18F-FDG. Six patients were excluded from the analysis because a malignant tumor could not be verified. In 38 patients (7 with colorectal cancer, 6 with pancreatic cancer, 9 with head-neck cancer, 4 with lymphomas, 3 with lung cancer, 3 with ovarian cancer, 4 with breast cancer, and 2 with prostatic cancer), 18F-FET PET and 18F-FDG PET were compared. RESULTS: 18F-FET was positive in only 13 of 38 patients (8 with head-neck cancer, 3 with breast cancer, and 2 with lung cancer), whereas 18F-FDG exhibited increased uptake in 37 of 38 patients. All squamous cell carcinomas were found to be 18F-FET-positive tumors (8 head-neck cancer and 2 lung cancer), whereas most adenocarcinomas were found to be 18F-FET-negative tumors. In patients with colorectal cancer, pancreatic cancer, ovarian cancer, prostatic cancer, and lymphomas, no increased 18F-FET uptake could be identified. All lesions that exhibited increased 18F-FET uptake also showed increased 18F-FDG uptake. No additional lesion was identified by 18F-FET PET but not by 18F-FDG PET. A subgroup analysis of patients with head-neck carcinomas allowed a better distinction between malignant and inflammatory tissues with 18F-FET than with 18F-FDG. CONCLUSION: 18F-FET is inferior to 18F-FDG as a PET tracer for general tumor diagnosis. Our preliminary results suggest rather selective uptake of 18F-FET in squamous cell carcinomas. Compared with 18F-FDG PET, 18F-FET PET may allow a better distinction between tumors and inflammatory tissues in patients with squamous cell carcinomas.     

Effect of Pentoxifylline and Tocopherol on Radiation Proctitis/Enteritis

BACKGROUND AND PURPOSE: Chronic radiation proctitis/enteritis is a relevant complication of pelvic irradiation, which is still mainly treated by supportive measures only. There is some evidence that the combined treatment with pentoxifylline and tocopherol might alter the pathogenesis of radiation-induced fibrosis. In a retrospective analysis the clinical benefit of the treatment with pentoxifylline/tocopherol on radiation-induced proctitis/enteritis was evaluated, compared to supportive care only. PATIENTS AND METHODS: Of 30 patients with radiation-induced proctitis/enteritis grade I-II according to the RTOG/EORTC toxicity criteria, 21 were treated with pentoxifylline and tocopherol. Depending on physician's decision nine patients received symptomatic treatment only. RESULTS: With pentoxifylline/tocopherol treatment 15/21 patients (71%) experienced a relief of their symptoms. A reduction from grade I/II to grade 0 toxicity was observed in seven and from grade II to grade I toxicity in eight patients. No improvement was seen in six patients. The median time to improvement with pentoxifylline and tocopherol treatment was 28 weeks. In three of nine patients who were treated supportively only, deterioration of symptoms occurred. Three patients experienced no amelioration, and three patients with grade I toxicity experienced a spontaneous relief of their symptoms (33%). CONCLUSION: The combination treatment with pentoxifylline and tocopherol seems to have a benefit in patients with grade I-II radiation-induced proctitis/enteritis. The optimal schedule of treatment duration is not yet clear. From the observations made in this study it is assumed the treatment should be given for 6-12 months at least. A prospective phase II study should be undertaken to evaluate optimal treatment duration.     

Source localization of mesial temporal interictal epileptiform discharges: Correlation with intracranial foramen ovale electrode recordings

OBJECTIVE: We have investigated the localization accuracy of low-resolution electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform discharges (IED) on a statistical basis by using clinical electroencephalographic (EEG) data of simultaneous scalp and intracranial foramen ovale (FO) electrode recordings. METHODS: We retrospectively analyzed the IED of 15 patients who underwent presurgical assessment for intractable temporal lobe epilepsy. All patients have subsequently undergone amygdalohippocampectomy. The scalp signals were averaged time-locked to the peak activity in bilateral 10-contact FO electrode recordings. Source modeling was carried out by using statistical non-parametric mapping (SNPM) of LORETA values and by calculating raw LORETA values of averaged IED. The results were compared to intracranial data obtained from FO electrode recordings. RESULTS: Two thousand six hundred and fifteen discharges could be attributed to 19 different patterns of intracranial mesial temporal IED. SNPM of LORETA revealed confined ipsilateral mesial temporal solutions for 14 (73.7%) and no significant solutions for five (26.3%) of these patterns. Raw LORETA current density distributions of the 19 averaged IED patterns revealed ipsilateral basal to lateral temporal solutions for the 14 IED patterns with a sufficient signal to noise ratio (SNR), but spurious results for those five IED with a low SNR. CONCLUSIONS: SNPM of LORETA but not LORETA analysis of averaged IED patterns accurately localizes the source generators of mesial temporal IEDs. SIGNIFICANCE: SNPM of raw LORETA values might be appropriate for localizing restricted mesial temporal lobe sources.     

Monoamine oxidase B single-photon emission tomography with [123I]Ro 43-0463: imaging in volunteers and patients with temporal lobe epilepsy

Imaging of monoamine oxidase of subtype B (MAO B) is of interest in various neurological diseases. In the past non-invasive assessment of MAO B has only been possible with positron emission tomography (PET) ligands. Given the limited availability of PET, a single-photon emission tomography (SPET) ligand would be desirable. In this study SPET imaging with the new MAO B inhibitor [¹²³I]Ro 43-0463 was performed in five volunteers and nine patients with temporal lobe epilepsy (TLE). In two volunteers a second study was performed 12 h following blockade with deprenyl. In the TLE patients the tracer was administered as bolus (n = 4) or as prolonged infusion (n = 5). The regional uptake pattern correlated well with the known distribution of MAO B. In the two blocking studies ligand uptake was substantially reduced compared with baseline. In the TLE patients increased uptake was found in the ipsilateral mesial temporal lobe and, surprisingly, in the ipsilateral putamen. This study indicates the potential of the new SPET ligand [¹²³I]Ro 43-0463 to map MAO B concentration in the human brain. The new finding of increased MAO B in the putamen of TLE patients needs further studies to elucidate its exact pathophysiology. Received 2 October and in revised form 29 December 1997     

Detection of secondary thalamic degeneration after cortical infarction using cis-4-18F-fluoro-D-proline.

The amino acid cis-4-(18)F-fluoro-D-proline (D-cis-(18)F-FPro) exhibits preferential uptake in the brain compared with its L-isomer, but the clinical potential of the tracer is as yet unknown. In this study we explored the cerebral uptake of D-cis-(18)F-FPro in rats with focal cortical infarctions. METHODS: Focal cortical infarctions were induced in different areas of the cortex of 20 Fisher CDF rats by photothrombosis (PT). At variable time points after PT (1 d to 4 wk), the rats were injected intravenously with D-cis-(18)F-FPro. For comparison, 12 rats were injected simultaneously with (3)H-deoxyglucose ((3)H-DG), 3 rats were injected with (3)H-methyl-L-methionine ((3)H-MET), and 2 rats were injected with (3)H-PK11195. Within 2 h after injection of the tracers, coronal cryosections of the brains were produced and evaluated by dual-tracer autoradiography. Lesion-to-brain ratios (L/B ratios) were calculated by dividing the maximal uptake in areas with increased tracer uptake by the mean uptake in normal brain tissue. Histologic slices were stained by toluidine blue and by immunostainings for glial fibrillary acidic protein (GFAP), CD68 for macrophages, and CD11b for microglia. RESULTS: Prominent uptake of D-cis-(18)F-FPro was found in ipsilateral thalamic nuclei (TN) and partially in the corpus striatum starting at 3 d after infarction with increasing L/B ratios up to 4 wk (mean L/B ratio +/- SD, 6.7 +/- 3.5). The involved TN varied with the site of the cortical lesion corresponding to their thalamocortical projections connecting them with their specific target region in the cerebral cortex. The TN were positive for CD11b and GFAP from day 7 onward, whereas uptake of (3)H-DG, (3)H-MET, and (3)H-PK11195 and immunostaining for CD68 were similar to that of normal brain. Furthermore, increased uptake of D-cis-(18)F-FPro was found in the area of the cortical infarctions (mean L/B ratio +/- SD, 12.1 +/- 8.1). From day 5 onward, the pattern of uptake was congruent with that of immunostaining for CD11b and CD68 but was different from that of GFAP. CONCLUSION: D-cis-(18)F-FPro appears to be a sensitive PET tracer for detection of secondary degeneration of TN after cortical injury. The uptake mechanisms of D-cis-(18)F-FPro remain to be elucidated, but the relationship to microglial activation suggests a diagnostic potential in various brain diseases.     

HIV-associated Cutaneous Kaposi's Sarcoma—Palliative Local Treatment by Radiotherapy

The increasing number of HIV-infected patients makes palliative treatment of HIV-associated Kaposi's sarcoma more common. We retrospectively evaluated a reduced fractionated radiotherapy with 20 Gy in respect to response rates and acute side-effects. From January 1992 to January 1995, 52 patients with HIV-associated Kaposi's sarcoma were treated with 133 single portals. Six weeks after the end of radiotherapy 42 patients with 124 portals were evaluable with respect to response rates and side-effects. Of the treated portals 32% were judged as complete responses (CR), 55% as partial responses (PR) and 12% as no change (NC). Skin reactions RTOG, grade I were seen in 74% of the patients. Compared with literature data the reduced overall dose of 20 Gy in 10 fractions led to a reduction of CRs by approximately 50% while the overall response rate remained equal. The success of radiotherapy for the nodular component of Kaposi's sarcoma can be improved, if a dose exceeding 20 Gy in 10 fractions is applied but at the cost of increasing side-effects in case that non-conventional fractionation schemes are used.     

Subchronic hepatotoxicity of selenomethionine ingestion in mallard ducks

Two-year-old male mallards (Anas platyrhynchos) received a control diet (0.2 ppm Se) or diets containing 1, 2, 4, 8, 16, or 32 ppm Se as selenomethionine for 14 wk. Se accumulated readily in the liver in a dose-dependent manner, reaching a mean concentration of 29 ppm (wet weight) in the 32 ppm group. Dietary Se of 2 ppm or greater increased plasma glutathione peroxidase activity. Mortality (10%) and histopathological effects, including bile duct hyperplasia and hemosiderin pigmentation of the liver and spleen, occurred in the 32 ppm group. These histopathological effects were accompanied by lower hemoglobin concentrations (16 and 32 ppm groups) and hematocrit (32 ppm group), and elevated plasma alkaline phosphatase activity (32 ppm group) indicative of cholestatic liver injury. Other manifestations of hepatotoxicity included significant linear dose responses for hepatic oxidized glutathione (GSSG) concentrations and ratio of GSSG to reduced glutathione (GSH). Means for both of these responses differed from controls in groups receiving 8-32 ppm Se. Mean hepatic GSH and malondialdehyde (a measure of lipid peroxidation) concentrations were significantly elevated in the 16 and 32 ppm groups. Subchronic effects of selenomethionine, which occurs in vegetation, are of particular interest with respect to the health of wild aquatic birds in seleniferous locations.     

Chemoradiation in Cervical Cancer with Cisplatin and High-Dose Rate Brachytherapy Combined with External Beam Radiotherapy Results of a Phase-II Study

BACKGROUND: In 1999, five randomized studies demonstrated that chemoradiation with cisplatin and low-dose rate (LDR) brachytherapy has a benefit in locally advanced cervical cancer and for surgically treated patients in high-risk situations. We evaluated the safety and efficacy of concomitant chemoradiation with cisplatin and high-dose rate (HDR) brachytherapy in patients with cervical cancer. PATIENTS AND METHODS: 27 patients were included in our phase-II trial: 13 locally advanced cases (group A) and 14 adjuvant-therapy patients in high-risk situations (group B). A definitive radiotherapy was performed with 25 fractions of external beam therapy (1.8 Gy per fraction/middle shielded after eleven fractions). Brachytherapy was delivered at HDR schedules with 7 Gy in point A per fraction (total dose 35 Gy) in FIGO Stages IIB-IIIB. The total dose of external and brachytherapy was 70 Gy in point A and 52-54 Gy in point B. All patients in stage IVA were treated without brachytherapy. Adjuvant radiotherapy was performed with external beam radiotherapy of the pelvis with 1.8 Gy single-dose up to 50.4 Gy. Brachytherapy was delivered at HDR schedules with two fractions of 5 Gy only in patients with tumor-positive margins or tumor involvement of the upper vagina. The chemotherapeutic treatment schedule provided six courses of cisplatin 40 mg/m2 weekly recommended in the randomized studies GOG-120 and -123. RESULTS: A total of 18/27 patients (66.7%) completed all six courses of chemotherapy. Discontinuation of radiotherapy due to therapy-related morbidity was not necessary in the whole study group. G3 leukopenia (29.6%) was the only relevant acute toxicity. There were no differences in toxicity between group A and B. Serious late morbidity occurred in 2/27 patients (7.4%). 12/13 patients (92.3%) with IIB-IVA cervical cancer showed a complete response (CR). 13/14 adjuvant cases (92.8%) are free of recurrence (median follow up: 19.1 months). CONCLUSION: Concomitant chemoradiation with cisplatin 40 mg/m2 weekly x 6 using HDR brachytherapy represents a promising treatment of cervical cancer with an acceptable toxicity.     

Lactated Ringer's Solution versus Hydroxyethyl Starch for Volume Replacement in Autologous Blood Donors with Cardiovascular Disease: A Controlled, Randomized Trial

Background and Objectives: The study was designed to evaluate whether volume replacement following blood donation can prevent arterial hypotension in autologous blood donors with cardiovascular disease. Materials and Methods: One hundred nineteen autologous blood donors with known cardiovascular disease were randomly allocated to receive, following withdrawal of 500 ml of blood, either no infusion (control group) or a 25 ml/min intravenous infusion of either 1,500 ml of lactated Ringer's solution (LRS) or 500 ml of 6% hydroxyethyl starch (HES). Starting before phlebotomy, arterial blood pressure was measured oscillometrically every 5 min until 90 min after donation. Results: Group means showed little difference between the groups in blood pressure throughout the monitoring period. The proportion of patients who at least once had a ≥20% decrease from baseline in systolic blood pressure was 3–5 times greater in the control group than in the LRS and the HES group (50 vs. 10 and 15%, respectively; p < 0.001 on χ² analysis for a 2 × 3 table). Systolic hypertensive episodes (≥ 20% increase over baseline) were observed more frequently in the LRS group than in the control and the HES group (41 vs. 10 and 18%, respectively; p=0.003). Conclusion: Both LRS and HES, administered at a volume ratio to blood loss of 3:1 and 1:1, respectively, significantly reduced the incidence of systolic hypotensive episodes in autologous blood donors with cardiovascular disease. LRS at a 3:1 volume ratio to blood loss was associated with a high rate of systolic hypertension.