Cardiac shockwave therapy in patients with chronic refractory angina pectoris.

BACKGROUND: Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT. METHODS: We included 33 patients (mean age 70 ± 7 years, mean left ventricular ejection fraction 55 ± 12 %) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the ischaemic zones (3-7 spots/session, 100 impulses/spot, 0.09 mJ/mm(2)) in an echocardiography-guided and ECG-triggered fashion. The protocol included a total of 9 treatment sessions (3 treatment sessions within 1 week at baseline, and after 1 and 2 months). Clinical assessment was performed using exercise testing, angina score (CCS class), nitrate use, myocardial scintigraphy, and cardiac magnetic resonance (CMR) 1 and 4 months after the last treatment session. RESULTS: One and 4 months after CSWT, sublingual nitrate use decreased from 10/week to 2/week (p < 0.01) and the angina symptoms diminished from CCS class III to CCS class II (p < 0.01). This clinical improvement was accompanied by an improved myocardial uptake on stress myocardial scintigraphy (54.2 ± 7.7 % to 56.4 ± 9.4 %, p = 0.016) and by increased exercise tolerance at 4-month follow-up (from 7.4 ± 2.8 to 8.8 ± 3.6 min p = 0.015). No clinically relevant side effects were observed. CONCLUSION: CSWT improved symptoms and reduced ischaemia burden in patients with end-stage coronary artery disease without relevant side effects. The study provides a solid basis for a randomised multicentre trial to establish CSWT as a new treatment option in end-stage coronary artery disease.

Low brown adipose tissue activity in endurance-trained compared with lean sedentary men.

BACKGROUND/OBJECTIVES: It has now been unequivocally demonstrated that humans possess functional brown adipose tissue (BAT) and that human BAT can be recruited upon chronic cold stimulation. Recruitment of BAT has been postulated as a potential strategy to counteract the current global obesity epidemic. Recently, it was shown in rodents that endurance exercise training could stimulate the recruitment of brown-like adipocytes within white adipose tissue (WAT) via exercise-induced myokines such as irisin (the cleaved circulating product of the type 1 membrane protein FNDC5) and interleukin-6 (IL-6). Our objective was to test whether endurance-trained athletes had increased cold-stimulated BAT activity and browning of subcutaneous WAT compared with lean sedentary males. SUBJECTS/METHODS: Twelve endurance-trained athletes and 12 lean sedentary males were measured during 2 h of mild cold exposure to determine cold-induced BAT activity via [(18)F]fluorodeoxyglucose-positron emission tomography-computed tomography ([(18)F]FDG-PET-CT) scanning. Skeletal muscle FNDC5 expression, as well as plasma irisin and IL-6 levels were determined. In addition, a subcutaneous abdominal WAT biopsy was taken to measure gene expression of several markers for browning of WAT. RESULTS: Cold-induced BAT activity was significantly lower in athletes, and no differences in gene expression of classical brown and beige adipocyte markers were detected in subcutaneous WAT between the groups. As expected, mRNA expression of FNDC5 in skeletal muscle was significantly higher in endurance athletes but plasma irisin and Il-6 levels were similar in both groups. CONCLUSIONS: These results indicate that chronic endurance exercise is not associated with brown and beige adipocyte recruitment; in fact endurance training appears to be linked to lower the metabolic activity of BAT in humans.

Selective internal radiation therapy (SIRT) in primary or secondary liver cancer.

Most patients with a history of common solid tumors will in the end develop liver metastases. Next to that, primary liver cancer, is a frequent cancer with fatal liver failure in the majority of patients. Selective internal radiation therapy (SIRT), has gradually been introduced over the recent years and is a promising, innovative albeit palliative treatment modality. The specific clinical background with regard to the indication and methodology of SIRT is presented and discussed in this paper.

First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer: a phase II study including molecular imaging.

BACKGROUND: Both bevacizumab and erlotinib have clinical activity in non-small-cell lung cancer (NSCLC). Preclinical data suggest synergistic activity. PATIENTS AND METHODS: Chemonaive patients with stage IIIb or IV non-squamous NSCLC were treated with bevacizumab 15 mg/kg every 3 weeks and erlotinib 150 mg daily until progression. Primary end point was non-progression rate (NPR) at 6 weeks. Tumor response was measured with computed tomography, 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). KRAS and EGFR mutations were assessed in tumor samples. RESULTS: Forty-seven patients were included. Median follow-up was 15.2 months. NPR at 6 weeks was 75%. Median progression-free survival (PFS) was 3.8 [95% confidence interval (CI) 2.3-5.4] months and median overall survival (OS) was 6.9 (95% CI 5.5-8.4) months. Toxicity was mainly mild. The presence of KRAS (n = 10) or EGFR mutations (n = 5) did not influence outcome. After 3 weeks of treatment, >20% decrease in standard uptake value as measured with positron emission tomography predicted for longer PFS (9.7 versus 2.8 months; P = 0.01) and >40% decrease in K(trans) as assessed by DCE-MRI did not predict for longer PFS. CONCLUSIONS: First-line treatment with bevacizumab and erlotinib in stage IIIb/IV NSCLC resulted in an NPR of 75%. OS was however disappointing. Early response evaluation with FDG-PET is the best predictive test for PFS.

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

AIM: The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. METHODS: Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. RESULTS: Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. CONCLUSION: The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

Targeted therapy in nuclear medicine--current status and future prospects.

In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explored.

A case of abdominal mesothelioma diagnosed by indium-III leucocyte scintigraphy.

We present a case of peritoneal mesothelioma that presented with fever of unknown origin and an elevation in the inflammatory parameters. Radiological imaging did not reveal a diagnosis. Because of tumour-associated inflammatory activity, indium-III leucocyte scintigraphy enabled us to establish a diagnosis. To our knowledge, the use of indium-III leucocyte scintigraphy in peritoneal mesothelioma has not been reported previously.

Vagus nerve stimulation in refractory epilepsy: SPECT activation study.

UNLABELLED: Left-sided vagus nerve stimulation (VNS) is an efficacious treatment for patients with refractory epilepsy. The exact mechanism of action remains to be elucidated. This study investigated the acute effects of initial VNS in patients with refractory complex partial epilepsy with or without secondary generalization (complex partial seizures [CPS] +/- SG) by means of a perfusion activation study with SPECT. METHODS: Twelve patients (mean age, 32.2 +/- 10.2 y; age range, 12-47 y) with a mean duration of CPS +/- SG of 19.8 +/- 10.0 y (range, 5-33 y) received VNS. All patients were considered unsuitable candidates for resective surgery because of nonlocalizing findings on presurgical evaluation. VNS efficacy was evaluated for patients with at least 4-mo follow-up. VNS-induced regional cerebral blood flow alterations were studied by a (99m)Tc-ethyl cysteinate dimer activation study with a single-day split-dose protocol before and immediately after an initial stimulation. Images were acquired on a triple-head camera with fanbeam collimators. After coregistration to a standardized template, both a semiquantitative analysis using predefined volumes of interest and a voxel-by-voxel analysis of the intrasubject activation (statistical parametric mapping) were performed. RESULTS: Seizure-frequency changes ranged from 100% decrease to 0% after VNS. The semiquantitative analysis revealed a consistent decrease of activity in the left thalamus (ratio stimulator on/off = 0.94 +/- 0.04; P = 0.005). These results were concordant with the voxel-by-voxel analysis in which a significant deactivation in the left thalamus was found with spread to the ipsilateral hippocampus. There was no statistically significant correlation between initial VNS-induced thalamic hypoperfusion and seizure reduction at maximum follow-up. CONCLUSION: Our findings are consistent with the hypothesis that acute VNS reduces seizure onset or propagation through inhibition of the thalamic relay center. Differences with limited H2(15)O PET data may be associated with temporal effects caused by a stimulation-induced local hemodynamic response and need further investigation. SPECT allows study of cerebral physiopathologic effects of vagus nerve electrostimulation in complex partial epilepsy.

The anti-tumoral activity of neoadjuvant intra-arterial 131I-lipiodol treatment for hepatocellular carcinoma: a pilot study.

BACKGROUND: The high recurrence rate after curative resection has stimulated the development of adjuvant treatment modalities, such as local embolization. This study was set up to investigate the anti-tumoral potential of neo-adjuvant 131I-lipiodol administration before liver transplantation. METHODS: In this preliminary, prospective study we treated 10 consecutive HCC patients by intra-arterial injection of 131I-lipiodol into the hepatic artery followed by liver transplantation within 1-9 months (mean 3.4). After hepatic catheterization, 1332-2146 MBq (mean 1887 MBq) or 36-58 mCi (mean 51 mCi) was instilled as selective as possible, depending on the distribution of the tumors: non-selectively in the hepatic artery propria (n = 4), selectively in the right and/or left hepatic artery (n = 3) or super-selectively in segmental arteries (n = 3). RESULTS: Anti-tumoral activity was regarded as obvious with 1) a strong decrease of alfa-fetoprotein (AFP), comparing the highest recorded value before and after 131I-lipiodol and/or 2) a downstaging in TNM classification on the posttherapy MRI as compared to the pre-therapy MRI and/or 3) tumors with > 50% necrosis on histo-pathology of the explanted liver, without previous chemoembolization. Either of these criteria were met by 5/10 (50%) of patients. A 4) downstaging in pTNM classification on histopathology compared to the TNM classification of the MRI and/or a 5) tumor necrosis of only 10-50% were regarded as possibly tumor-related but were not accepted as a single criteria of anti-tumoral activity. This was seen in 3/10 (30%) of patients. Clinical side-effects of the 131I-lipiodol therapy were generally mild with a temperature rise in two cases, nausea without vomiting in another two and upper back pain in one patient. In one patient progressive liver failure developed one week after 131I-lipiodol therapy necessitating premature liver transplantation after 4 weeks. CONCLUSION: With the use of stringent anti-tumoral criteria, this study shows evidence of an anti-tumoral effect in 50% of patients. Our data support the evaluation on larger patient numbers to confirm the promising anti-tumoral activity of 131I-lipiodol in HCC patients candidated for liver transplantation.

Predictive value of 99Tcm-DTPA captopril scintigraphy in patients with a solitary kidney and reduced kidney function.

The aim of this study was to determine if the qualitative 99Tcm-DTPA captopril radionuclide test (CRT) can help predict the acute detrimental effect of angiotensin-converting enzyme (ACE) inhibitors on renal function in hypertensive patients with solitary kidneys and chronic renal failure. Between 1991 and 1996, eight consecutive patients (6 males, 2 females) aged 27-73 years (mean 49.8 years) with known chronic renal failure and a solitary kidney referred for ACE treatment were included. 99Tcm-DTPA renography was performed at baseline and 1 h after the administration of 25 mg captopril within 1 week of each other. The CRT was performed in accordance with the criteria of the Working Party on the Diagnostic Criteria of Renovascular Hypertension with Captopril Renography. A beneficial or detrimental effect of subsequent ACE inhibitor treatment on renal function was determined by long-term follow-up (> or = 2 years). The CRT accurately predicted outcome in all eight patients subsequently treated with ACE inhibitors. In conclusion, our results suggest a role for qualitative 99Tcm-DTPA CRT in the prediction of renal function in patients with a solitary kidney and chronic renal failure subsequently treated with ACE inhibitors.

Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours.

AIM: The aim of the study was to determine the equivalent total body dose (ETBD) using the cytokinesis-blocked micronucleus assay in 22 131 I-meta-iodobenzylguanidine (131 I-MIBG) therapies (18 neuroblastoma, mean 5097 MBq, SD 1591; and four carcinoid tumours, mean 7681 MBq, SD 487). The results are correlated with the total body radiation dose according to the Medical Internal Radiation Dosimetry (MIRD) formalism. METHODS: For each patient, blood samples were taken immediately before and 1 week after 131I-MIBG therapy. The first blood sample was irradiated in vitro with 60Co gamma-rays to determine the dose-response curve. Micronuclei were scored in 1000 binucleated cells. By using the dose-response curve the ETBD was derived from the increase in micronuclei after 131I-MIBG therapy (second blood sample). Based on three consecutive biplanar scans taken at 3, 6 and 9 days post-administration respectively, the total body dose following the MIRD formalism was calculated. RESULTS: The micronucleus assay was evaluable in only 14 out of 22 131I-MIBG therapies due to cell division inhibition caused by previous chemotherapy treatments and lymphocyte dilution due to blood transfusions given shortly after 131I-MIBG therapy. For these 14 therapies, the mean micronucleus yield after 131I-MIBG therapy was significantly increased (P < 0.01) with a mean of 92 (SD 77) for neuroblastoma patients and with a mean of 35 (SD 8) for carcinoid patients. The increase observed in the present study is greater than previously observed after 131I therapy and 89Sr therapy but much lower than after external beam radiotherapy. For all patients treated with multiple therapies, the initial increase in micronucleus yield had at least partially recovered by the time of the next therapy. This might be explained by an increased turnover of lymphocytes. A mean ETBD of 0.95 Gy (SD 0.55) for neuroblastoma patients and a mean of 0.46 Gy (SD 0.09) for carcinoid patients was calculated. A reasonable correlation (R = 0.87) between the ETBD and the MIRD dose was obtained. The slope value of 0.75 can be explained by the low dose rate effect. CONCLUSIONS: The observation in the present study of important inter-individual variability in the total body dose, with the possibility of high dose values, suggests the necessity of individual dosimetry when administering 131I-MIBG therapy, especially considering that generally more than one therapy is given to each patient.

Intra-arterial radionuclide therapy for liver tumours: effect of selectivity of catheterization and 131I-Lipiodol delivery on tumour uptake and response.

Several authors have demonstrated the good tolerance of hepatic intra-arterial 131I-Lipiodol therapy and report survival rates of 21-25% after 1 year in inoperable patients. This study explored the possibility that more selective hepatic arterial instillation could be a strategy for increasing tumoural uptake and response of 131I-Lipiodol. Between June 1999 and September 2001 we selected 24 patients: 14 received a selective instillation of 131I-Lipiodol to the proper hepatic artery (SEL group); and 10 received a hyperselective instillation in the right or left hepatic artery (HYP-SEL group). The individual 131I-Lipiodol activity as a per cent of the injected activity per millilitre of tumour (%IA/ml tumour) was correlated with the selectivity of instillation in 28 tumours and with tumour response in 24 tumours. Differences in tumour response or tumour uptake between the SEL and HYP-SEL groups were not significant. In general, we observed a %IA/ml tumour of 0.05-2.6% for the uptake of 131I-Lipiodol. The uptake was significantly higher in responsive disease than in stable or progressive disease (P=0.002). A large tumour volume was invariably related to low uptake of 131I-Lipiodol and progressive disease (P=0.008). In conclusion, our study does not support the general use of hyper-selective or super-selective intra-arterial administration of 131I-Lipiodol. This result may be extrapolated to similar types of intra-arterial, loco-regional hepatic radionuclide therapy.

Bone marrow content measured in radioimmune bone marrow scintigraphy: intra- and inter-observer variability.

The aim of this study was to assess the possible quantification of vertebral residual bone marrow content relative to the bone marrow content of a non-irradiated vertebra. This method is based on the vertebral count activity, measured using radioimmune bone marrow scintigraphy. First, however, we had to evaluate intra- and inter-observer variability. In three patients who underwent radioimmune bone marrow scintigraphy, two independent observers measured the count density in 51 (15 lumbar and 36 thoracic) vertebrae using a manually drawn region of interest. To evaluate intra- and inter-observer variability, we calculated the means and standard deviations of the differences between measurements. Bland-Altman plots were drawn for all vertebrae as well as for three subgroups of vertebrae (the upper thoracic spine, D1-D6; the lower thoracic spine, D7-D12; and the lumber spine, L1-L5). For all vertebrae, the mean (+/- S.D.) difference, expressed as a percentage of the overall mean, was -0.44 +/- 3.3% for observer 1 and -0.3 +/- 2.1% for observer 2 for intra-observer variability; inter-observer variability varied from 0.55 +/- 3.9% to 1.28 +/- 3.7%. On the Bland-Altman plots, the data points were evenly distributed above and below the 0-line and the linear regression equations matched the line of equality almost perfectly. This pattern was observed for all the vertebrae as well as for the subgroups of vertebrae. In conclusion, our results show that the intra- and inter-observer variabilities are not great, confirming that this technique is simple and robust and can be used for further quantification of bone marrow content in the axial skeleton.

The classical stroop interference task as a prefrontal activation probe: a validation study using 99Tcm-ECD brain SPECT.

This study investigated the feasibility of brain single photon emission computed tomography (SPECT) functional imaging in a neuropsychological test setting, following a single-day protocol with a split-dose paradigm. The Stroop Color Word Test (SCWT) is an example of a well-documented prefrontal activation task. In a split-dose protocol, ten right-handed healthy volunteers were injected twice with 370 MBq 99Tcm-ethyl cysteinate dimer while performing consecutively both series of card-reading of the SCWT. Images were reconstructed using filtered back-projection and normalized to a standard template in Talairach coordinates. Statistical Parametric Mapping (SPM96) was used to determine voxelwise significant changes. A first activation cluster was found in the left medial prefrontal cortex, consisting of the gyrus cinguli anterior and the gyrus frontalis medius and superior. A second activation cluster included the right gyrus frontalis dorsalis and medius. These findings confirm to a large extent the results of previous functional magnetic resonance imaging, positron emission tomography studies of Stroop-like tasks. The choice and validity of various methodological characteristics of the experimental design leading to these results is critically discussed. It is concluded that brain SPECT activation with the Stroop Color Word Test under standard neuropsychological conditions in healthy volunteers, is both technically and practically feasible.

Depression and anxiety during isolation and radionuclide therapy.

The combination of a diagnosis of malignancy and hospitalization, isolation and radioactivity of a radionuclide therapy may have an important effect on the psychological equilibrium of patients and may hamper compliance and acceptability. We performed a psychiatric evaluation in order to study psycho-pathological manifestations and underlying personality related vulnerabilities. During radioisolation, 48 patients (24 male, 24 female; mean age 57.8 years) with a malignant (n=26) or non-malignant (n=22) pathology who needed isolation for radionuclide therapy, completed a series of questionnaires in order to assess anxiety (Spielberger State and Trait Anxiety Inventory; STAI), depression (Beck Depression Inventory; BDI), hopelessness (Beck Hopelessness Scale; BHS), personality characteristics (Temperament and Character Inventory; TCI) and coping strategies (Utrecht's Coping List; UCL). Compared to patients with low state anxiety, patients who experienced a high level of state anxiety showed higher levels of depression (t=-2.10; P=0.04) and hopelessness (t=-4.20; P=<0.001). Their personality was characterized by significantly higher scores on harm avoidance (t=-2.78; P=0.008) and lower scores on self-directedness (t=3.12; P=0.003). Coping strategies were more passive (t=-2.43; P=0.02), avoiding (t=-2.15; P=0.04) and less well aimed (t=2.64; P=0.01). Surprisingly, the nature of disease (malignant versus non-malignant) did not influence these results, nor was there a difference between males and females, age, years of education, having a relationship or not, or the duration of hospitalization. Thus, contrary to what may be expected in isolation with radionuclide therapy, subgroups such as women, elderly, cancer patients or lower educated people do not, a priori, exhibit a higher state anxiety level. Our study shows these levels to be closely related to individual personality traits and coping strategies that are inadequate for the situation. Screening for trait anxiety before admission can be easily done and may guide interventions aimed at increasing patient comfort and acceptability.

SPECT neuropsychological activation procedure with the Verbal Fluency Test in attempted suicide patients.

Performance on the Verbal Fluency Test, as a measure of the ability of initiating processes, is reduced in depressed suicidal patients. The hampered results in this prefrontal executive task parallel the reduction in prefrontal blood perfusion and metabolism in depressed subjects. A neuropsychological activation study with the verbal fluency paradigm could evaluate a possible blunted increase in perfusion in the prefrontal cortex in depressed suicidal patients. Twenty clinically depressed patients who had recently attempted suicide and 20 healthy volunteers were included in a single photon emission computed tomography (SPECT) split-dose activation study following a verbal fluency paradigm. Statistical parametric mapping was used to determine voxelwise significant changes. Differences in regional cortical activation between the letter fluency and category fluency tasks in attempted suicide patients were found. These patients showed a blunted increase in perfusion in the prefrontal cortex. Methodological restrictions concerning group uniformity, medication bias and subjective effort of the participants are discussed. Our findings indicate a blunted increase in prefrontal blood perfusion as a possible biological reason for reduced drive and loss of initiative in attempted suicide patients.

Dosimetry from organ to cellular dimensions.

While the conventional Medical Internal Radiation Dose (MIRD) approach is useful for estimating approximate organ absorbed doses in diagnostic applications of isotopes, this strategy is suited neither to the exacting requirements of targeted radionuclide therapy nor to radiopharmaceuticals with a non-uniform activity distribution. For the individual treatment planning of patients treated with common radionuclides emitting high energy betas, the individual activity distribution has to be obtained from CT-SPECT images and the doses to the target organs and critical tissues have to be calculated by point-kernel methods. Due to the stochastic nature, alpha-radioimmunotherapy (alpha-RIT) requires microdosimetric calculations with Monte Carlo on a realistic model of the source and target tissue at the micrometer level. For a prediction of the biological effects of intracellular labelling with Auger electron emitters an accurate subcellular modelling including the DNA structure at the nanometre level with knowledge of the target for the considered biological effect is necessary.

Metastases seen on SPECT imaging despite a normal planar bone scan.

Although bone scintigraphy is an extremely sensitive method for the detection of focal bone disease, small lesions below the resolution of planar imaging may be missed. This is a report of a patient with carcinoma of the breast who showed tumor progression 1 year after initial treatment. Complete evaluation was performed in order to detect the origin of increased level of a tumor marker. Although planar bone scintigraphy could not demonstrate any lesion in the spine, multiple metastases were detected in the lumbar and the thoracic spines on SPECT imaging. Only some of these lesions were seen with MRI. Repeat planar bone imaging 6 weeks later showed multiple bone lesions in the lumbar and thoracic areas.

Generalized bone marrow metastases. High liver uptake on bone marrow immunoscintigraphy associated with extramedullary hematopoiesis.

Increased hepatic uptake and absent bone marrow uptake on bone marrow immunoscintigraphy has been reported after the formation of human antimurine antibodies. A case of generalized bone marrow metastases is presented, in whom an elevated liver uptake on bone marrow immunoscintigraphy proved to be associated with extramedullary hematopoiesis. Extramedullary hematopoiesis should be included as a possible cause of a disproportionately elevated liver uptake on bone marrow immunoscintigraphy, especially on initial studies, or on repeat studies with low human antimurine antibody titers. Tc-99m labeled BW 250/183 immunoscintigraphy may aid in the localization of suspected sites of extramedullary hematopoiesis.

Increase in brown adipose tissue activity after weight loss in morbidly obese subjects.

CONTEXT: Stimulation of thermogenesis in brown adipose tissue (BAT) is a potential target to treat obesity. We earlier demonstrated that BAT activity is relatively low in obese subjects. It is unknown whether BAT can be recruited in adult humans. OBJECTIVE: To study the dynamics of BAT, we observed BAT activity in morbidly obese subjects before and after weight loss induced by bariatric surgery. DESIGN: This was an observational prospective cohort study. SETTING: The study was conducted at a referral center. PATIENTS: Ten morbidly obese subjects eligible for laparoscopic adjustable gastric banding surgery were studied before and 1 yr after bariatric surgery. MAIN OUTCOME MEASURE: The main outcome measure was BAT activity, as determined after acute cold stimulation using (18)F-fluorodeoxyglucose positron emission tomography and computed tomography. RESULTS: Before surgery, only two of 10 subjects showed active BAT. One year after surgery, the number of subjects with active BAT was increased to five. After weight loss, BAT-positive subjects had significantly higher nonshivering thermogenesis compared with BAT-negative subjects (P < 0.05). CONCLUSIONS: The results show that in humans BAT can be recruited in the regions in which it was also reported in lean subjects before. These results for the first time show recruitment of BAT in humans and may open the door for BAT-targeted treatments of obesity.