(188)Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study.

PURPOSE: (188)Re-HEDP is indicated for the treatment of pain in patients with painful osteoblastic bone metastases, including hormone-refractory prostate cancer patients. Efficacy may be improved by adding chemotherapy to the treatment regimen as a radiation sensitizer. The combination of (188)Re-HEDP and capecitabine (Xeloda(R)) was tested in a clinical phase I study. METHODS: Patients with hormone-refractory prostate cancer were treated with capecitabine for 14 days (oral twice daily in a dose escalation regimen with steps of 1/3 of 2,500 mg/m(2) per day in cohorts of three to six patients, depending on toxicity). Two days later patients were treated with 37 MBq/kg (188)Re-HEDP as an intravenous injection. Six hours after treatment post-therapy scintigraphy was performed. Urine was collected for 8 h post-injection. Follow-up was at least 8 weeks. The primary end-point was to establish the maximum tolerable dose (MTD) of capecitabine when combined with (188)Re-HEDP. Secondary end-points included the effect of capecitabine on the biodistribution and pharmacokinetics of (188)Re-HEDP. RESULTS: Three patients were treated in the first and second cohorts, each without unacceptable toxicity. One of six patients in the highest cohort experienced unacceptable toxicity (grade 4 thrombopaenia). The MTD proved to be the maximum dose of 2,500 mg/m(2) per day capecitabine. No unexpected toxicity occurred. Capecitabine had no effect on uptake or excretion of (188)Re-HEDP. CONCLUSION: Capecitabine may be safely used in combination with (188)Re-HEDP in a dose of 2,500 mg/m(2) per day and 37 MBq/kg, respectively. Efficacy will be further studied in a phase II study using these dosages.

Increased serotonin and dopamine transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder shown by 123I-beta-(4-iodophenyl)-tropane SPECT.

UNLABELLED: There is circumstantial evidence for the involvement of serotonergic and dopaminergic systems in the pathophysiology of social anxiety disorder. In the present study, using SPECT imaging we examined the (123)I-beta-(4-iodophenyl)-tropane binding potential for the serotonin and dopamine transporters in patients with a generalized social anxiety disorder and in age- and sex-matched healthy controls. METHODS: Twelve psychotropic medication-naïve patients with social anxiety disorder, generalized type (5 women and 7 men) and 12 sex- and age-matched healthy controls were studied. Volumes of interest were constructed on MRI-coregistered SPECT scans. Binding ratios were compared using the Mann-Whitney U test. Possible correlations between binding patterns and symptomatology were assessed using the Spearman rank correlation coefficient. RESULTS: Significantly higher binding potentials were found for the serotonin in the left and right thalamus of patients. Patients had also a significantly higher binding potential for the dopamine transporter in the striatum. CONCLUSION: The present study provided direct evidence for abnormalities in both the dopaminergic and the serotonergic systems in patients with generalized social anxiety disorder.

Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases.

PURPOSE: (153)Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated. METHODS: Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg (153)Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before (153)Sm-EDTMP treatment. Urine was collected 48 h after injection of (153)Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of (153)Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied. RESULTS: The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 +/- 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 +/- 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with (153)Sm-EDTMP. CONCLUSION: Zoledronic acid treatment does not influence (153)Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe.

Long-term toxicity of holmium-loaded poly(L-lactic acid) microspheres in rats.

The aim of this study was to get insight into the toxic effects of holmium-166-loaded poly(L-lactic acid) microspheres (Ho-PLLA-MS) which have very interesting features for treatment of liver malignancies. Acute, mid- and long-term effects were studied in healthy Wistar rats by evaluating clinical, biochemical and tissue response. Rats were divided into four treatment groups: sham, decayed neutron-irradiated Ho-PLLA-MS, non-irradiated Ho-PLLA-MS and PLLA-MS. After implantation of the microspheres into the liver of the rats, the animals were monitored (body weight, temperature and liver enzymes) for a period of 14-18 months. Some of the rats that received previously neutron-irradiated Ho-PLLA-MS were periodically scanned with magnetic resonance imaging (MRI) to see if holmium was released from the microspheres. After sacrifice, the liver tissue was histologically evaluated. Bone tissue was subjected to neutron-activation analysis in order to examine whether accumulation of released holmium in the bone had occurred. No measurable clinical and biochemical toxic effects were observed in any of the treatment groups. Furthermore, histological analyses of liver tissue samples only showed signs of a slight chronic inflammation and no significant differences in the tissue reaction between rats of the different treatment groups could be observed. The non-irradiated PLLA-MS and Ho-PLLA-MS stayed intact during the study. In contrast, 14 months after administration, the neutron-irradiated Ho-PLLA-MS was not completely spherical anymore, indicating that degradation had started. However, the holmium loading had not been released as was illustrated with MRI and affirmed by neutron-activation analysis of bone tissue. In conclusion, neutron-irradiated Ho-PLLA-MS does not provoke any toxic reaction and can be applied safely in vivo.

Spect measurements of regional cerebral perfusion and carbondioxide reactivity: correlation with cerebral collaterals in internal carotid artery occlusive disease.

BACKGROUND: The aim of the present study was to assess the regional variation in cerebral perfusion, vasomotor reactivity (VMR) and the role of cerebral collaterals in patients with symptomatic internal carotid artery (ICA). METHODS: Seventeen functionally independent patients (60+/-9 years, mean+/-SD) with a unilateral symptomatic internal carotid artery occlusion and a <30% contralateral ICA stenosis were investigated. (99 m) Tc-hexamethyl propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) was performed to study cerebral blood flow in rest and during a CO(2) challenge in the cerebellum, temporal lobe, occipital lobe, basal ganglia, frontal lobe and parietal lobe. Time of flight and phase contrast MRA were used to study collateral flow via circle of Willis. RESULTS: In rest, cerebral perfusion on the side ipsilateral to the ICA occlusion was decreased compared with the contralateral side in the basal ganglia (p<0.05), frontal lobe (p<0.01) and parietal lobe (p<0.01). During a CO(2) challenge only the ipsilateral frontal lobe demonstrated a perfusion decrease compared with the contralateral frontal lobe (p<0.05). Furthermore, in patients without collateral flow via the anterior circle of Willis the perfusion of the ipsilateral frontal lobe was significantly decreased (p<0.01) during the CO(2) challenge and crossed cerebellar diaschisis with a decreased perfusion on the contralateral cerebellar hemisphere was detected (p<0.05). No cerebral blood flow (CBF) differences were found for present/absent collateral flow via the posterior communicating artery. CONCLUSION: Regional assessment of cerebral perfusion and VMR with SPECT demonstrated the heterogeneity of cerebral hemodynamics and the importance of collateral flow via the anterior circle of Willis.

Hybrid scatter correction applied to quantitative holmium-166 SPECT.

Ho-166 is a combined beta-gamma emitter of which the betas can be used therapeutically. From the 81 keV gammas of Ho-166, SPECT images can be obtained, which give opportunities to guide Ho-166 therapy. Accurate reconstruction of Ho-166 images is currently hampered by photopeak-scatter in the patient, down-scatter in the detector, collimator and patient caused by the 1.4 MeV photons and by bremsstrahlung. We developed and validated a method for quantitative SPECT of Ho-166 that involves correction for both types of scatter plus non-uniform attenuation correction using attenuation maps. Photopeak-scatter (S) is compensated for by a rapid 3D Monte Carlo (MC) method that is incorporated in ordered subset (OS) reconstruction of the emission data, together with simultaneous correction for attenuation (A) and detector response (D); this method is referred to as OS-ADS. Additionally, for correction of down-scatter, we use a 14 keV wide energy window centred at 118 keV (OS-ADSS). Due to a limited number of available energy windows, the same 118 keV energy window was used for down-scatter correction of the simultaneously acquired Gd-153 transmission data. Validations were performed using physical phantom experiments carried out on a dual-head SPECT system; Gd-153 transmission line sources were used for acquiring attenuation maps. For quantitative comparison of OS-ADS and OS-ADSS, bottles filled with Ho-166 were placed in both a cylindrical phantom and an anthropomorphic thorax phantom. Both OS-ADS and OS-ADSS were compared with an ordered subset reconstruction without any scatter correction (OS-AD). Underestimations of about 20% in the attenuation map were reduced to a few per cent after down-scatter correction. The average deviation from the true activity contained in the bottles was +72% with OS-AD. Using OS-ADS, this average overestimation was reduced to +28% and with OS-ADSS the deviation was further reduced to 16%. With OS-AD and OS-ADS, these numbers were more sensitive to the choice of volumes of interest than with OS-ADSS. For the reconstructed activity distributions, erroneous background activity found with OS-AD was reduced by a factor of approximately 2 by applying OS-ADS and reduced by a factor of approximately 4 by applying OS-ADSS. The combined attenuation, photopeak-scatter and down-scatter correction framework proposed here greatly enhanced the quantitative accuracy of Ho-166 imaging, which is of the uppermost importance for image-guided therapies. It is expected that the method, with adapted window settings, also can be applied to other isotopes with high energy peaks that contaminate the photopeak data, such as I-131 or In-111.

Repeated [131I]metaiodobenzylguanidine therapy in two patients with malignant pheochromocytoma.

CONTEXT: Approximately 10% of pheochromocytomas are malignant with a 5-yr survival rate of less than 40%. Promising results have been published on single high-dosage [131I]metaiodobenzylguanidine ([131I]MIBG) treatment for malignant pheochromocytoma. We present our experience with multiple intermediate-dosage [131I]MIBG therapy instead of single high-dosage therapy. SETTING AND PATIENTS: The study took place at University Medical Centers and included two patients (one male, 36 yr of age, and one female, 43 yr of age) with widely spread metastatic pheochromocytoma and bad prognosis because of liver and lung metastases. INTERVENTIONS: Instead of a single high dosage, these two patients were treated with multiple intermediate dosages of [131I]MIBG. The first patient received 37 GBq (1 Ci) [131I]MIBG in five sessions [7400 MBq (200 mCi) each; interval range, 2-11 months]; the second patient received 66.6 GBq (1.8 Ci) [131I]MIBG in 12 sessions [5550 MBq (150 mCi) each; interval range, 2-14 months]. OUTCOME MEASURES: We measured efficacy, toxicity, and survival. RESULTS: Both patients had a complete symptomatic response and a partial tumor volume response. The first patient had a partial biochemical response, the second a complete biochemical response. In both cases, toxicity has been confined to nausea during treatment. Hematological toxicity was minimal, and both patients stayed euthyroid. The survival (so far) of these patients was 5 yr (clinical case 1) and 16 yr (clinical case 2) after initial diagnosis. CONCLUSIONS: Repeated intermediate-dosage [131I]MIBG treatment appears to be a reliable and well-tolerated radionuclide therapy and might be a useful adjunct in patients with malignant pheochromocytoma, providing longstanding palliation and prolonged survival.

U-SPECT-I: a novel system for submillimeter-resolution tomography with radiolabeled molecules in mice.

UNLABELLED: A major advance in biomedical science and diagnosis was accomplished with the development of in vivo techniques to image radiolabeled molecules, but limited spatial resolution has slowed down applications to small experimental animals. Here, we present a SPECT system (U-SPECT-I) dedicated to radionuclide imaging of murine organs at a submillimeter resolution. METHODS: The high performance of U-SPECT-I is based on a static triangular detector setup, with a cylindric imaging cavity in the center and 75 gold micropinhole apertures in the cavity wall. The pinholes are focused on a small volume of interest such as the mouse heart or spine to maximize the detection yield of gamma-photons. Three-dimensional molecular distributions are iteratively estimated using the detector data and a statistical reconstruction algorithm that takes into account system blurring and data noise to increase resolution and reduce image noise. RESULTS: With 0.6-mm-diameter pinholes, the maximum fraction of detected photons emitted by a point source (peak sensitivity) is 0.22% for a 15%-wide energy window and remains higher than 0.12% in the central 12 mm of the central plane. In a resolution phantom, radioactively filled capillaries as small as 0.5 mm and separated by 0.5 mm can be distinguished clearly in reconstructions. Projection data needed for the reconstruction of cross sections of molecular distributions in mouse organs can readily be obtained without the need for any mechanical movements. Images of a mouse spine show 99mTc-hydroxymethylene diphosphonate uptake down to the level of tiny parts of vertebral processes. These are separated clearly from the vertebral and intervertebral foramina. Using another tracer, one can monitor myocardial perfusion in the left and right ventricular walls, even in structures as small as the papillary muscles. CONCLUSION: U-SPECT-I allows discrimination between molecular concentrations in adjacent volumes of as small as about 0.1 muL, which is significantly smaller than can be imaged by any existing SPECT or PET system. Our initial in vivo images of the mouse heart and spine show that U-SPECT-I can be used for novel applications in the study of dynamic biologic systems with a clear projection to clinical applications. The combination of high resolution and detection efficiency of U-SPECT-I opens up new possibilities for the suborgan-level study of radiotracers in mouse models.

Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine.

Functional imaging studies have pointed to a role of the orbitofrontal cortex (OFC), striatum and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Effective treatment has been found to change brain activity within this circuitry. The aim of the present study was to explore possible differential effects of OCD responders and non-responders to drug treatment on the regional cerebral blood flow (rCBF). Measurements of rCBF were carried out in 15 out of 22 patients with OCD who completed an open-label trial with fluvoxamine. Patients were studied with 99mTc-HMPAO single photon emission computed tomography (SPECT) before and after 12 weeks of treatment. In addition, structural magnetic resonance imaging was obtained on all patients. Regions of interest comprised the OFC, caudate nucleus, putamen and thalamus. Seven patients responded to treatment. Levels of rCBF decreased significantly in the left caudate nucleus and the left and right putamen in both responders and non-responders to treatment. In responders, but not in non-responders, a significant decrease in rCBF was found in the right thalamus. Pre-treatment cerebellar and whole brain HMPAO uptake was significantly higher in responders to treatment compared with non-responders. We suggest that the thalamus plays a central role in the response to drug treatment.

Bone marrow dosimetry and safety of high 131I activities given after recombinant human thyroid-stimulating hormone to treat metastatic differentiated thyroid cancer.

UNLABELLED: Recombinant human thyroid-stimulating hormone (rhTSH) recently was introduced as a radioiodine administration adjunct that avoids levothyroxine (LT-4) withdrawal and resultant hypothyroidism. The pharmacokinetics of 131I after rhTSH administration are known to differ from those after LT-4 withdrawal but are largely nondelineated in the radioiodine therapy setting. We therefore sought to calculate the red marrow absorbed dose of high therapeutic activities of 131I given after rhTSH administration to patients with metastatic or inoperable locally recurrent differentiated thyroid cancer. We also sought to evaluate the clinical and laboratory effects of this therapy on the bone marrow. METHODS: Fourteen consecutive patients received in total 17 131I treatments (7.4 GBq). Blood and urine samples were obtained at fixed intervals, and their activities were measured in a well counter. Based on blood activity, renal clearance of the activity, and residence times in red marrow and the remainder of the body, the red marrow absorbed dose was calculated using the MIRD schema. Additionally, we monitored for potential hematologic toxicity and compared platelet counts before and 3 mo after treatment. RESULTS: The mean +/- SD absorbed dose per unit of administered (131)I in the red marrow was 0.16 +/- 0.07 mGy/MBq. The corresponding total red marrow absorbed dose was 1.15 +/- 0.52 Gy (range, 0.28-1.91 Gy). In none of the patients was hematologic toxicity observed. The mean +/- SD platelet count (n = 13 treatments) was 243 +/- 62 x 10(9)/L before treatment and 233 +/- 87 x 10(9)/L 3 mo later, a slight and statistically insignificant decrease. After rhTSH-aided administration of high activities of 131I, the bone marrow absorbed dose remained under 2 Gy, the level long considered the safety threshold for all radioiodine therapy. CONCLUSION: Our specific findings imply that when clinically warranted, rhTSH should allow an increase in the therapeutic radioiodine activity. Such an increase might improve efficacy while preserving safety and tolerability; this possibility should be assessed in further studies.

186Re-HEDP for metastatic bone pain in breast cancer patients.

Two-thirds of patients with metastatic cancer suffer from pain. Pain originating from skeletal metastases is the most common form of cancer-related pain. Bone pain, often exacerbated by pressure or movement, limits the patient's autonomy and social life. Pain palliation with bone-seeking radiopharmaceuticals has proven to be an effective treatment modality in patients with metastatic bone pain. These bone-seeking radiopharmaceuticals are extremely powerful in treating scattered painful bone metastases, for which external beam radiotherapy is impossible because of the large field of irradiation. (186)Re-hydroxyethylidene diphosphonate (HEDP) is a potentially useful radiopharmaceutical for this purpose, having numerous advantageous characteristics. Bone marrow toxicity is limited and reversible, which makes repetitive treatment safe. Studies have shown encouraging clinical results of palliative therapy using (186)Re-HEDP, with an overall response rate of ca. 70% in painful bone metastases. It is effective for fast palliation of painful bone metastases from various tumours and the effect tends to last longer if patients are treated early in the course of their disease. (186)Re-HEDP is at least as effective in breast cancer patients with painful bone metastases as in patients with metastatic prostate cancer. It is to be preferred to radiopharmaceuticals with a long physical half-life in this group of patients, who tend to have more extensive haematological toxicity since they have frequently been pretreated with bone marrow suppressive chemotherapy. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life.

Monte Carlo-based down-scatter correction of SPECT attenuation maps.

Combined acquisition of transmission and emission data in single-photon emission computed tomography (SPECT) can be used for correction of non-uniform photon attenuation. However, down-scatter from a higher energy isotope (e.g. 99mTc) contaminates lower energy transmission data (e.g. 153Gd, 100 keV), resulting in underestimation of reconstructed attenuation coefficients. Window-based corrections are often not very accurate and increase noise in attenuation maps. We have developed a new correction scheme. It uses accurate scatter modelling to avoid noise amplification and does not require additional energy windows. The correction works as follows: Initially, an approximate attenuation map is reconstructed using down-scatter contaminated transmission data (step 1). An emission map is reconstructed based on the contaminated attenuation map (step 2). Based on this approximate 99mTc reconstruction and attenuation map, down-scatter in the 153Gd window is simulated using accelerated Monte Carlo simulation (step 3). This down-scatter estimate is used during reconstruction of a corrected attenuation map (step 4). Based on the corrected attenuation map, an improved 99mTc image is reconstructed (step 5). Steps 3-5 are repeated to incrementally improve the down-scatter estimate. The Monte Carlo simulator provides accurate down-scatter estimation with significantly less noise than down-scatter estimates acquired in an additional window. Errors in the reconstructed attenuation coefficients are reduced from ca. 40% to less than 5%. Furthermore, artefacts in 99mTc emission reconstructions are almost completely removed. These results are better than for window-based correction, both in simulation experiments and in physical phantom experiments. Monte Carlo down-scatter simulation in concert with statistical reconstruction provides accurate down-scatter correction of attenuation maps.

Scintigraphic assessment of early and late parotid gland function after radiotherapy for head-and-neck cancer: a prospective study of dose-volume response relationships.

PURPOSE: To investigate the value of scintigraphy as an indirect measurement of parotid function after radiotherapy (RT). METHODS AND MATERIALS: Ninety-six patients with primary or postoperative RT for various malignancies in the head-and-neck region were prospectively evaluated. Parotid gland scintigraphy was performed before RT and 6 weeks and 1 year after RT. The uptake, excretion fraction of the saliva from the parotid gland to the oral cavity (SEF), and the ratios of uptake and SEF after and before treatment were calculated. CT-based treatment planning was used to derive dose-volume histograms of the parotid glands. To establish the effects of both the radiation dose and the volume of the parotid gland irradiated, the normal tissue complication probability model proposed by Lyman was fit to the data. RESULTS: The mean maximal uptake of 192 parotid glands decreased significantly from 3329 counts (ct)-/s before RT to 3084 ct/s and 3005 ct/s at 6 weeks and 1 year after RT. The SEF before treatment was 44.7%. The SEF decreased to 18.7% at 6 weeks after RT, but recovered to a SEF of 32.4% at 1 year after RT. A significant correlation was found between the uptake 1 year after RT and the mean parotid dose. The reduction in post-RT SEF correlated significantly with the mean parotid gland dose. The normal tissue complication probability model parameter TD50 was found to be 29 and 43 Gy at 6 weeks and 1 year after RT, respectively, when a complication was defined as a posttreatment SEF parotid ratio of <45%. CONCLUSIONS: The effects of radiation on parotid gland function using scintigraphy could be well established. A statistically significant correlation between the SEF ratio and the mean parotid dose was shown, with some recovery of function at 1 year after RT, comparable with the flow results. When direct flow measurements are not feasible, parotid scintigraphy appears to be a good indicator of gland function.

Suspected thyroid stunning after radioiodine-131 scanning in a patient with a diffuse goiter.

A case of suspected thyroid stunning is presented in a previously hyperthyroid patient with a diffuse goiter, who had undergone a 185 MBq (131)I-NaI thyroid scan shortly before a (99m)Tc-pertechnetate scan. A less likely alternative hypothesis is the development of early hypothyroidism, 3.5 weeks after a modest (131)I dose.

Tumour dosimetry and response in patients with metastatic differentiated thyroid cancer using recombinant human thyrotropin before radioiodine therapy.

The development of recombinant human thyrotropin (rhTSH) has given clinicians new options for diagnostic follow-up and treatment of patients with differentiated thyroid cancer (DTC). This paper evaluates the tumour dosimetry and response following -iodine-131 treatment of metastatic thyroid cancer patients after rhTSH stimulation instead of classical hormone withdrawal-induced hypothyroidism. Nineteen consecutive (131)I treatments in 16 patients were performed after rhTSH stimulation. All patients had undergone a near-total thyroidectomy followed by an ablative dosage of (131)I. They all suffered from metastatic or recurrent disease showing tumoral (131)I uptake on previous post-treatment scintigraphy. Dosimetric calculations were performed using (131)I tumour uptake measurements from post-treatment (131)I scintigrams and tumour volume estimations from radiological images. Response was assessed by comparing pre-treatment serum thyroglobulin (Tg) level with the Tg level 3 months post treatment. In 18 out of 19 treatments, uptake of (131)I in metastatic or recurrent lesions was seen. The median tumour radiation dose was 26.3 Gy (range 1.3-368 Gy), and the median effective half-life was 2.7 days (range 0.5-6.5 days). Eleven of 19 treatments (10/16 patients) were evaluable for response after 3 months. (131)I therapy with rhTSH resulted in a biochemical partial response in 3/11 or 27% of treatments (two patients), biochemical stable disease in 2/11 or 18% of treatments and biochemical progressive disease in 6/11 or 55% of treatments. Our study showed that although tumour doses in DTC patients treated with (131)I after rhTSH were highly variable, 45% of treatments led to disease stabilisation or partial remission when using rhTSH in conjunction with (131)I therapy, without serious side-effects and with minimal impact on quality of life. RhTSH is therefore adequately satisfactory as an adjuvant tool in therapeutic settings and is especially suitable in advanced recurrent or metastatic DTC patients who may be intolerant to TSH stimulation by levothyroxine withdrawal.

Use of a dual-head coincidence camera and 18F-FDG for detection and nodal staging of non-small cell lung cancer: accuracy as determined by 2 independent observers.

UNLABELLED: The accurate detection of lung carcinoma and the determination of its stage remain significant clinical problems. (18)F-FDG PET has been shown to improve detection and staging of lung cancer and to prevent unnecessary invasive procedures. Positron imaging with dual-head gamma cameras may not be as sensitive as PET, but recent studies have shown good results with these cameras. METHODS: In the present study, we investigated 100 patients, 76 of whom were male and 24 female (mean age +/- SD, 60.7 +/- 9.4 y), with suspected non-small cell lung cancer. (18)F-FDG scanning was performed using a dual-head coincidence camera 1 h after the intravenous injection of 185 MBq of (18)F-FDG. For 46 patients, attenuation correction was also performed. Two independent observers unaware of clinical status analyzed all imaging studies. TNM classification was assigned after surgical staging. RESULTS: In 44 patients with clinically suspected bronchogenic carcinoma, no evidence of malignancy was found. However, in 56 patients a pulmonary neoplasm was demonstrated. At interobserver analysis, a kappa value of 0.94 (P < 0.0001) was found for detection of the primary tumor and a kappa value of 0.63 (P < 0.0001) was found for mediastinal staging. A sensitivity of 96%, a specificity of 93%, and an accuracy of 95% were found for detection of pulmonary neoplasm. Assessment of lymph node involvement showed a sensitivity of 50%, a specificity of 92%, and an accuracy of 77%. The sensitivity of CT in assessing lymph node involvement was 36%, the specificity was 86%, and the accuracy was 67%. Attenuation correction provided more anatomic information, but no differences were seen between attenuation-corrected and non-attenuation-corrected images for detecting lesions or lymph node involvement. CONCLUSION: The present study confirms earlier data showing that (18)F-FDG scans obtained with dual-head coincidence cameras are useful in the detection of non-small cell lung cancer and less suitable for staging of lymph node involvement, with accuracy comparable to that of CT.

Comparison of methods for thyroid volume estimation in patients with Graves' disease.

Individualised dosage models are frequently applied for radioiodine therapy in patients with Graves' hyperthyroidism, especially in Europe. In these dosage schemes the thyroid volume is an important parameter. Thyroid volume determinations are usually made with ultrasonography or with thyroid scintigraphy, although the accuracy of planar scintigraphy for this purpose is not well established. The aim of this study was to compare the accuracy of three modalities for the determination of the thyroid volume in patients with Graves' disease: planar scintigraphy (PS), single-photon emission tomography (SPET) and ultrasonography (US). These three modalities were compared with magnetic resonance imaging (MRI) as the gold standard. Thyroid volume estimations were performed in 25 patients with Graves' disease. The PS images were subjected to filtering and thresholding, and a standard surface formula was used to calculate the thyroid volume. With SPET the iteratively reconstructed thyroid images were filtered, and after applying a threshold method an automatic segmentation algorithm was used for the volume determinations. Thyroid volumes were estimated from the US images using the ellipsoid volume model for multiple two-dimensional measurements. For MRI, thyroid segmentation was performed manually in gadolinium-enhanced T1-weighted images and a summation-of-areas technique was used for the volume measurements. The thyroid volumes calculated with MRI were 25.0+/-13.8 ml (mean+/-SD, range 7.0-56.3 ml). PS correlated poorly with MRI ( R(2)=0.61) and suffered from a considerable bias (-4.0+/-17.6 ml). The differences between PS and MRI volume estimations had a very large spread (33+/-58%). For SPET both the correlation with MRI ( R(2)=0.84) and the bias (1.8+/-11.9 ml) were better than for PS. US had by far the best correlation with MRI ( R(2)=0.97) and the best precision, but the bias (6.8+/-7.5 ml) was not negligible. In conclusion, SPET is preferred over PS for accurate measurements of thyroid volume. US is the most accurate of the three modalities, if a correction is made for bias.

The PLACORHEN study: a double-blind, placebo-controlled, randomized radionuclide study with (186)Re-etidronate in hormone-resistant prostate cancer patients with painful bone metastases. Placebo Controlled Rhenium Study.

UNLABELLED: (186)Re-1,1-hydroxyethylidene diphosphonate (etidronate) can be used for the palliative treatment of metastatic bone pain. A randomized, placebo-controlled study using (186)Re-etidronate was conducted on end-stage prostate cancer patients with metastatic bone pain. METHODS: Pain relief was assessed using an electronic diary containing questions reflecting the multidimensional character of chronic pain. The diary was marked twice daily for a maximum of 14 wk (2 wk before and 12 wk after the injection). Pain response was determined using a specific decision rule in which pain intensity, medication index, and daily activities were the core determinants. A positive response day was defined as a day on which pain intensity was reduced > or = 25% compared with baseline values, while medication index and daily activities were at least constant, or on which pain intensity was reduced < 25% and medication index or daily activities improved > or = 25%, without worsening of the remaining factor. The total response (%) was defined as the number of positive response days divided by the number of days of follow-up. RESULTS: Of the 111 included patients, 79 were evaluable (43 (186)Re-etidronate, 36 placebo). Thirty-two patients were excluded from the analysis because of incomplete datasets. The total response of the patients treated with (186)Re-etidronate varied from 0% to 96% (mean, 27%, or 23/84 d). In the placebo group, the total response varied from 0% to 80% (mean, 13%, or 11/84 d; Mann-Whitney U test, P < 0.05). The number of patients who requested radiotherapy was higher in the placebo group (67%) than in the (186)Re-etidronate group (44%) (relative risk, 1.51; Fisher's exact test, P = 0.069). CONCLUSION: This randomized controlled trial confirmed that, compared with placebo, (186)Re-etidronate resulted in a significantly longer pain response in the treatment of bone pain from metastasized prostate cancer.

Nasal mucociliary transport: new evidence for a key role of ciliary beat frequency.

OBJECTIVES/HYPOTHESIS: Mucociliary transport is an important defense mechanism of the respiratory tract. Nonetheless, the factors determining mucociliary transport are only partially understood. Ciliary beat frequency is assumed to be one of the main parameters, although the experimental evidence remains inconclusive. STUDY DESIGN: Comparing influences on mucociliary transport to influences on ciliary beat frequency. METHODS: The present study measures the effects on mucociliary transport of two ciliary beat frequency-inhibiting compounds (0.1% xylometazoline and 0.9% NaCl) and a ciliary beat frequency enhancer (0.1% salbutamol). The measurements were performed by a technetium-99m nebulizing scintigraphic method. The experiments were carried out in 15 healthy young volunteers. RESULTS: The 0.1% xylometazoline appeared to slow ciliary transport, although the decrease was not significant (P = .44). The 0.9% NaCl did reduce mucociliary transport significantly (P = .033). The 0.1% salbutamol resulted in a highly significant increase of mucociliary transport (P = .009). Xylometazoline brings about drastic changes in the nasal cavity, both anatomically and physiologically. Any comparison of mucociliary transport before and after using this vasoconstrictive agent must take this effect into account. CONCLUSIONS: The present study demonstrates a significant similarity in the effects of NaCl and salbutamol on ciliary beat frequency in vitro and on mucociliary transport in vivo. The evidence from our experiments suggests that ciliary beat frequency is a determining factor in the mucociliary transport rate in the nose.

Cost-effectiveness of dual-head 18F-fluorodeoxyglucose PET for the detection of recurrent laryngeal cancer.

The study is based upon 80 patients, suspected of having recurrent laryngeal cancer, who underwent an 18F-FDG PET study on a coincidence camera and a laryngoscopic biopsy under general anaesthesia. The potential value of 18F-FDG PET in the detection of local relapses of laryngeal cancer after radiotherapy by use of a coincidence camera was prospectively assessed, and a cost-effectiveness analysis was performed retrospectively. The effectiveness of 18F-FDG PET is reflected in sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) using comparison with the biopsy results as a gold standard. In case of a negative biopsy result, follow-up was continued for a minimum of one year. The results showed a sensitivity of 100%, a specificity of 85%, a PPV of 87%, and a NPV of 100%. Costs per patient of a 18F-FDG PET scan were 682 euro, whereas the saved costs by reducing CT-scans and panendoscopies were 618 euro. In this scenario implementation of 18F-FDG PET scintigraphy in the detection of recurrent laryngeal cancer has additional costs of 64 euro per patient. However, panendoscopy related complications, and potential improvement in quality of life due to early detection of recurrent disease were not taken into account in this study. In conclusion, the technical efficacy of 18F-FDG PET in the detection of recurrent laryngeal cancer is high. 18F-FDG PET is more accurate than CT, and in addition the cost-effectiveness ratio of 18F-FDG PET lies within an acceptable range and has further improvement potential when a quality of life factor is included in a prospective cost-effectiveness analysis.