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[ 177 Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Since the time of regulatory approval, however, real-world data have been lacking. This study investigated the efficacy, safety, and outcome predictors of [ 177 Lu]Lu-PSMA-617 at a major U.S. academic center. Methods: Patients with mCRPC who received [ 177 Lu]Lu-PSMA-617 at the Johns Hopkins Hospital outside clinical trials were screened for inclusion. Patients who underwent [ 177 Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate-specific antigen (PSA) response (≥50% decline), PSA progression-free survival (PFS), and overall survival (OS). Toxicity data were evaluated according to the Common Terminology Criteria for Adverse Events version 5.03. The study tested the association of baseline circulating tumor DNA mutational status in homologous recombination repair, PI3K alteration pathway, and aggressive-variant prostate cancer-associated genes with treatment outcome. Baseline PSMA PET/CT images were analyzed using SelectPSMA, an artificial intelligence algorithm, to predict treatment outcome. Associations with the observed treatment outcome were evaluated. Results: All 76 patients with PSMA-positive mCRPC who received [ 177 Lu]Lu-PSMA-617 met the inclusion criteria. A PSA response was achieved in 30 of 74 (41%) patients. The median PSA PFS was 4.1 mo (95% CI, 2.0-6.2 mo), and the median OS was 13.7 mo (95% CI, 11.3-16.1 mo). Anemia of grade 3 or greater, thrombocytopenia, and neutropenia were observed in 9 (12%), 3 (4%), and 1 (1%), respectively, of 76 patients. Transient xerostomia was observed in 23 (28%) patients. The presence of aggressive-variant prostate cancer-associated genes was associated with a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P = 0.040). No other associations were observed between circulating tumor DNA mutational status and treatment outcomes. Eighteen of 71 (25%) patients classified by SelectPSMA as nonresponders had significantly lower rates of PSA response than patients classified as likely responders (6% vs. 51%; P < 0.001), a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P < 0.001), and a shorter OS (median, 6.3 vs. 14.5 mo; P = 0.046). Conclusion: [ 177 Lu]Lu-PSMA-617 offered in a real-world setting after regulatory approval in the United States demonstrated antitumor activity and a favorable toxicity profile. Artificial-intelligence-based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background and Objective: Primary hepatocellular carcinoma (HCC) poses a significant threat to human health. The mean overall survival (OS) of HCC is approximately 15.8 months whereas the 6-month and 1-year OS rates are only 71.6% and 49.7%, respectively. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) has been widely used for the management of several solid cancers; however, HCC frequently displays low 18 F-FDG uptake; approximately 50% of HCC cases do not take up 18 F-FDG. Therefore, 18 F-FDG PET is not considered very useful for the visualization of HCC and is not currently a recommended standard imaging modality for HCC. Conversely, 18 F-FDG PET/CT has been reported to be clinically important in the management, staging, and prognosis of HCC patients. Currently, reports relating to 18 F-FDG uptake in HCC are unclear and controversial. There is an urgent need to clarify the efficacy of 18 F-FDG PET for the management of HCC., Methods: The PubMed database was searched for all articles on the application of 18 F-FDG PET/CT imaging for human HCC up to December 2021. The following search terms were used: 'Hepatocellular carcinoma', '[18F]FDG PET/CT', 'Hypoxia', '[ 11 C]Choline'., Key Content and Findings: In this review, we re-evaluate the potential hypoxia-dependent uptake mechanism of 18 F-FDG in HCC and review the usefulness of 18 F-FDG PET/CT for identifying, managing, and investigating the biological properties of HCC., Conclusions: 18 F-FDG PET/CT is very useful for HCC visualization, management, and the evaluation of biological properties. A negative test for 18 F-FDG uptake is not meaningless and may reflect a relatively better outcome. 18 F-FDG-positive lesions indicate a significantly less favorable prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1420/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Alzheimer's disease (AD) is the main cause of dementia, with its diagnosis and management remaining challenging. Amyloid positron emission tomography (PET) has become increasingly important in medical practice for patients with AD. To integrate and update previous guidelines in the field, a task group of experts of several disciplines from multiple countries was assembled, and they revised and approved the content related to the application of amyloid PET in the medical settings of cognitively impaired individuals, focusing on clinical scenarios, patient preparation, administered activities, as well as image acquisition, processing, interpretation and reporting. In addition, expert opinions, practices, and protocols of prominent research institutions performing research on amyloid PET of dementia are integrated. With the increasing availability of amyloid PET imaging, a complete and standard pipeline for the entire examination process is essential for clinical practice. This international consensus and practice guideline will help to promote proper clinical use of amyloid PET imaging in patients with AD., Competing Interests: Conflicts of InterestThe authors declare that they have no conflict of interest., (© The Author(s) 2022.)

The study identifies the importance of positron emission tomographic (PET) and anatomic imaging modalities and their individual performances in detecting succinate dehydrogenase A ( SDHA) -related metastatic pheochromocytoma and paraganglioma (PPGL). The detection rates of PET modalities- 68 Ga-DOTATATE, 18 F-FDG, and 18 F-FDOPA-along with the combination of computed tomography (CT) and magnetic resonance imaging (MRI) are compared in a cohort of 11 patients with metastatic PPGL in the setting of a germline SDHA mutation. The imaging detection performances were evaluated at three levels: overall lesions, anatomic regions, and a patient-by-patient basis. 68 Ga-DOTATATE PET demonstrated a lesion-based detection rate of 88.6% [95% confidence interval (CI), 84.3-92.5%], while 18 F-FDG, 18 F-FDOPA, and CT/MRI showed detection rates of 82.9% (CI, 78.0-87.1%), 39.8% (CI, 30.2-50.2%), and 58.2% (CI, 52.0-64.1%), respectively. The study found that 68 Ga-DOTATATE best detects lesions in a subset of patients with SDHA- related metastatic PPGL. However, 18 F-FDG did detect more lesions in the liver, mediastinum, and abdomen/pelvis anatomic regions, showing the importance of a combined approach using both PET modalities in evaluating SDHA -related PPGL.

Positron emission tomography (PET) represents molecular imaging for non-invasive phenotyping of physiological and biochemical processes in various oncological diseases. PET imaging with 18 F-fluorodeoxyglucose ( 18 F-FDG) for glucose metabolism evaluation is the standard imaging modality for the clinical management of lymphoma. One of the 18 F-FDG PET applications is the detection and pre-treatment staging of lymphoma, which is highly sensitive. 18 F-FDG PET is also applied during treatment to evaluate the individual chemo-sensitivity and accordingly guide the response-adapted therapy. At the end of the therapy regiment, a negative PET scan is indicative of a good prognosis in patients with advanced Hodgkin's lymphoma and diffuse large B-cell lymphoma. Thus, adjuvant radiotherapy may be alleviated. Future PET studies using non- 18 F-FDG radiotracers, such as 68 Ga-labeled pentixafor (a cyclic pentapeptide that enables sensitive and high-contrast imaging of C-X-C motif chemokine receptor 4), 68 Ga-labeled fibroblast activation protein inhibitor (FAPI) that reflects the tumor microenvironment, and 89 Zr-labeled atezolizumab that targets the programmed cell death-ligand 1 (PD-L1), may complement 18 F-FDG and offer essential tools to decode lymphoma phenotypes further and identify the mechanisms of lymphoma therapy., Competing Interests: Conflicts of InterestThe authors declare that they have no conflicts of interest., (© International Human Phenome Institutes (Shanghai) 2022.)

Targeted radionuclide therapies (TRT) using 131 I-metaiodobenzylguanidine ( 131 I-MIBG) and peptide receptor radionuclide therapy ( 177 Lu or 90 Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity- 131 I-MIBG therapy was approved by the FDA and both 177 Lu-DOTATATE and 131 I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs., (©2021 American Association for Cancer Research.)

Context: Pheochromocytomas/paragangliomas (PPGLs) are neuroendocrine tumors that can secrete norepinephrine (NE). Brown adipose tissue (BAT) activation is mediated through the action of NE on β-adrenoceptors (β-ARs). In some malignancies, BAT activation is associated with higher cancer activity., Objective: To study the relationship between BAT activation and PPGL clinical outcomes., Design: A retrospective case-control study that included 342 patients with PPGLs who underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18F-FDG PET/CT) imaging at the National Institutes of Health (NIH). We excluded all patients with parasympathetic tumors and those who underwent 18F-FDG PET/CT after PPGL resection. Scans of 205 patients were reviewed by 2 blinded nuclear medicine physicians; 16 patients had BAT activation on 18F-FDG PET/CT [7.80%; age 27.50 (15.00-45.50) years; 10 female/6 male; body mass index [BMI] 24.90 [19.60-25.35] kg/m2). From the remaining 189 patients, we selected 36 matched controls (age 34.4 [25.4-45.5] years; 21 female/15 male; BMI 25.0 [22.0-26.0] kg/m2)., Primary Outcome Measure: Overall survival., Results: The presence of active BAT on 18F-FDG PET/CT was associated with decreased overall survival when compared with the control group (HRz 5.80; 95% CI, 1.05-32.05; P = 0.02). This association remained significant after adjusting for the SDHB mutation. Median plasma NE in the BAT group was higher than the control group [4.65 vs 0.55 times above the upper limit of normal; P < 0.01]. There was a significant association between higher plasma NE levels and mortality in PPGLs in both groups., Conclusions: Our findings suggest that the detection of BAT activity in PPGL patients is associated with higher mortality. We suggest that BAT activation could either be reflecting or contributing to a state of increased host stress that may predict poor outcome in metastatic PPGL., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Pheochromocytoma and paraganglioma (PHEO/PGL) are rare neuroendocrine tumors which may cause potentially life-threatening complications, with about a third of cases found to harbor specific gene mutations. Thus, early diagnosis, treatment, and meticulous monitoring are of utmost importance. Because of low incidence of succinate dehydrogenase complex subunit A ( SDHA )-related metastatic PHEO/PGL, currently there exists insufficient clinical information, especially with regards to its diagnostic and treatment characteristics. Methods: Ten patients with SDHA -related metastatic PHEO/PGL were followed-up prospectively and/or retrospectively between January 2010-July 2018. They underwent biochemical tests ( n = 10), 123 I-MIBG ( n = 9) scintigraphy, and multiple whole-body positron emission tomography/computed tomography (PET/CT) scans with 68 Ga-DOTATATE ( n = 10), 18 F-FDG ( n = 10), and 18 F-FDOPA ( n = 6). Results: Our findings suggest that these tumors can occur early and at extra-adrenal locations, behave aggressively, and have a tendency to develop metastatic disease within a short period of time. None of our patients had a family history of PHEO/PGL, making them appear sporadic. Nine out of 10 patients showed abnormal PHEO/PGL-specific biochemical markers with predominantly noradrenergic and/or dopaminergic phenotype, suggesting their utility in diagnosing and monitoring the disease. Per patient detection rates of 68 Ga-DOTATATE ( n = 10/10), 18 F-FDG ( n = 10/10), 18 F-FDOPA ( n = 5/6) PET/CT, and 123 I-MIBG ( n = 7/9) scintigraphy were 100, 100, 83.33, and 77.77%, respectively. Five out of 7 123 I-MIBG positive patients had minimal 123 I-MIBG avidity or detected very few lesions compared to widespread metastatic disease on 18 F-FDG PET/CT, implying that diagnosis and treatment with 123/131 I-MIBG is not a good option. 68 Ga-DOTATATE PET/CT was found to be superior or equal to 18 F-FDG PET/CT in 7 out of 10 patients and hence, is recommended for evaluation and follow-up of these patients. All 7 out of 7 patients who received conventional therapies (chemotherapy, somatostatin analog therapy, radiation therapy, 131 I-MIBG, peptide receptor radionuclide therapy) in addition to surgery showed disease progression. Conclusion: In our cohort of patients, SDHA -related metastatic PHEO/PGL followed a disease-course similar to that of SDHB -related metastatic PHEO/PGL, showing highly aggressive behavior, similar imaging and biochemical phenotypes, and suboptimal response to conventional therapies. Therefore, we recommend careful surveillance of the affected patients and a search for effective therapies.

Objective: To assess the clinical value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large vessel vasculitis (LVV) and comparator subjects., Methods: Patients with Takayasu arteritis and giant cell arteritis were studied, along with a comparator group consisting of patients with hyperlipidemia, patients with diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG-PET imaging, and patients with LVV underwent serial imaging at 6-month intervals. We calculated sensitivity and specificity of FDG-PET interpretation for distinguishing patients with clinically active LVV from comparator subjects and from patients with disease in clinical remission. A qualitative summary score based on global arterial FDG uptake, the PET Vascular Activity Score (PETVAS), was used to study associations between activity on PET scan and clinical characteristics and to predict relapse., Results: A total of 170 FDG-PET scans were performed in 115 participants (56 patients with LVV and 59 comparator subjects). FDG-PET distinguished patients with clinically active LVV from comparator subjects with a sensitivity of 85% (95% confidence interval [95% CI] 69, 94) and a specificity of 83% (95% CI 71, 91). FDG-PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71 [58%]). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with activity on PET scan. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high PETVAS than in those with a low PETVAS (55% versus 11%; P = 0.03) over a median follow-up period of 15 months., Conclusion: FDG-PET provides information about vascular inflammation that is complementary to, and distinct from, clinical assessment in LVV. FDG-PET scan activity during clinical remission was associated with future clinical relapse., (© 2017, American College of Rheumatology.)

Following tremendous economic progress, society in China is also undergoing fundamental changes, as is the healthcare system. Currently the training of Chinese young doctors and their future work placement are all undergoing re-structuring. We compiled some thoughts and opinions on the topic of 'should clinicians in China engage in research?', and publish them as a special report in this issue of Quantitative Imaging in Medicine and Surgery (QIMS). The contributors included some editorial members of this journal, and a few personal friends. Besides a few minor linguistic corrections, opinions from the contributors have not been edited, as we want authors' to write their own independent views. However, it is possible there is a selection bias of the contributors of this paper; more likely those who are interested in the medical research are selected and therefore the views of the contributors may not be generalizable. To compare the structure and funding of China with other countries, authors from UK, The Netherlands, France, and USA are also invited.

Unlabelled: This study revisited (18)F-fluorodeoxyglucose ((18)F-FDG) uptake and its relationship to hypoxia in various tumor models., Methods: We generated peritoneal carcinomatosis and subcutaneous xenografts of colorectal cancer HT29, breast cancer MDA-MB-231, and non-small cell lung cancer A549 cell lines in nude mice. The partial oxygen pressure (pO2) of ascites fluid was measured. (18)F-FDG accumulation detected by digital autoradiography was related to tumor hypoxia visualized by pimonidazole binding and glucose transporter-1 (GLUT-1) in frozen tumor sections., Results: Ascites pO2 was 0.90 ± 0.53 mm Hg. Single cancer cells and clusters suspended in ascites fluid as well as submillimeter serosal tumors stained positive for pimonidazole and GLUT-1 and had high (18)F-FDG uptake. In contrast, (18)F-FDG uptake was significantly lower in normoxic portion (little pimonidazole binding or GLUT-1 expression) of larger serosal tumors or subcutaneous xenografts, which was not statistically different from that in the liver., Conclusions: Glucose demand ((18)F-FDG uptake) in severely hypoxic ascites carcinomas and hypoxic portion of larger tumors is significantly higher than in normoxic cancer cells. Warburg effect originally obtained from Ehrlich ascites carcinoma may not apply to normoxic cancer cells. Our findings may benefit the better understanding of (18)F-FDG PET in oncology application., (Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.)

Osteonecrosis of the jaw is usually a potential complication of bisphosphonate therapy. In a cancer patient, this disease entity can be misdiagnosed as a metastatic lesion. Our aim is to make clinicians aware of bisphosphonate associated osteonecrosis of the jaw to prevent misdiagnosis and initiate proper treatment at the earliest. We present the case of a breast cancer patient with multiple bony metastases and a jaw lesion presumed to be metastases. After no response to palliative radiation, repeat radiological imaging studies revealed osteonecrosis of the jaw. Correlating a patient's clinical information with findings on diagnostic imaging studies, such as SPECT bone and CT scans, can help identify this potential complication of bisphosphonate treatment. Early diagnosis helps minimize unnecessary biopsies and allows for the proper treatment to be instituted.

Purpose: The objective is to validate the combination of 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) and (18)F-fluorodeoxyglucose ((18)F-FDG) as a "novel" positron emission tomography (PET) tracer for better visualization of cancer cell components in solid cancers than individual radiopharmaceutical., Methods: Nude mice with subcutaneous xenografts of human non-small cell lung cancer A549 and HTB177 cells and patients with lung cancer were included. In ex vivo study, intratumoral radioactivity of (18)F-FDG, (18)F-FLT, and the cocktail of (18)F-FDG and (18)F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, (18)F-FDG PET and (18)F-FLT PET were conducted in the same subjects (mice and patients) 10 to 14 hours apart. Second, PET scan was also performed 1 hour after one tracer injection; subsequently, the other was administered and followed the second PET scan in the mouse. Finally, (18)F-FDG and (18)F-FLT cocktail PET scan was also performed in the mouse., Results: When injected individually, (18)F-FDG highly accumulated in hypoxic zones and high (18)F-FLT in proliferative cancer cells. In case of cocktail injection, high radioactivity correlated with hypoxic regions and highly proliferative and normoxic regions. PET detected that intratumoral distribution of (18)F-FDG and (18)F-FLT was generally mismatched in both rodents and patients. Combination of (18)F-FLT and (18)F-FDG appeared to map more cancer tissue than single-tracer PET., Conclusions: Combination of (18)F-FDG and (18)F-FLT PET imaging would give a more accurate representation of total viable tumor tissue than either tracer alone and would be a powerful imaging strategy for cancer management.

Unlabelled: (18)F-FDG, (18)F-fluorothymidine, and (18)F-misonidazole PET scans have emerged as important clinical tools in the management of cancer; however, none of them have demonstrated conclusive superiority. The aim of this study was to compare the intratumoral accumulation of (18)F-FDG, (18)F-fluorothymidine, and (18)F-misonidazole and relate this to specific components of the tumor microenvironment in mouse models of human non-small cell lung cancer (NSCLC)., Methods: We used NSCLC A549 and HTB177 cells to generate subcutaneous and peritoneal xenografts in nude mice. Animals were coinjected with a PET radiotracer, pimonidazole (hypoxia marker), and bromodeoxyuridine (proliferation marker) intravenously 1 h before animal euthanasia. Tumor perfusion was assessed by Hoechst 33342 injection, given 1 min before sacrifice. The intratumoral distribution of PET radiotracers was visualized by digital autoradiography and related to microscopic visualization of proliferation, hypoxia, perfusion, stroma, and necrosis., Results: NSCLC xenografts had complex structures with intermingled regions of viable cancer cells, stroma, and necrosis. Cancer cells were either well oxygenated (staining negatively for pimonidazole) and highly proliferative (staining positively for bromodeoxyuridine) or hypoxic (pimonidazole-positive) and noncycling (little bromodeoxyuridine). Hypoxic cancer cells with a low proliferation rate had high(18)F-FDG and (18)F-misonidazole uptake but low (18)F-fluorothymidine accumulation. Well-oxygenated cancer cells with a high proliferation rate accumulated a high level of (18)F-fluorothymidine but low (18)F-FDG and(18)F-misonidazole. Tumor stroma and necrotic zones were always associated with low (18)F-FDG, (18)F-misonidazole, and (18)F-fluorothymidine activity., Conclusion: In NSCLC A549 and HTB177 subcutaneously or intraperitoneally growing xenografts, (18)F-fluorothymidine accumulates in well-oxygenated and proliferative cancer cells, whereas (18)F-misonidazole and (18)F-FDG accumulate mostly in poorly proliferative and hypoxic cancer cells. (18)F-FDG and (18)F-misonidazole display similar intratumoral distribution patterns, and both mutually exclude (18)F-fluorothymidine.

A 48-year-old male smoker presented with a chief complaint of persistent cough for three months. A CT scan revealed only a large right paratracheal mass. The plan was to obtain histological confirmation of suspected lung cancer via bronchoscopy and mediastinoscopy. A whole body 18F-FDG (2-deoxy-2-[18F]fluoro-D-glucose) PET Scan was ordered for staging and localization of the most accessible biopsy site. There was a large, intense hypermetabolic focus corresponding to the paratracheal lesion seen on CT, as well as a lesion in the right adrenal gland. There was also a superficial, subcutaneous hypermetabolic lesion in the mid-back. The subcutaneous lesion, which previously had not been noted, was biopsied and proved to be metastatic adenocarcinoma consistent with the lung primary. This case illustrates the clinical utility of reporting soft tissue abnormalities, which may provide an alternative, more readily accessible location for biopsy that is both safer and less expensive than bronchoscopy or mediastinoscopy.

One hundred one males and 95 females referred for thallium stress testing were administered Spielberger's State-Trait Anger Expression Inventory (STAXI), the Ho scale cynicism items, the Cynical Beliefs Scale, and Bendig's Manifest Anxiety Scale. A subset of 53 males and 43 females was rated by their spouses by means of STAXI. Based on the thallium findings and their medical history, patients were classified either as healthy, or as having documented CHD, or as questionable. Patients' STAXI and cynicism measures were submitted to a principal-components analysis which yielded three factors: Impulsive Anger-out. Inwardly experienced anger, and Cynicism. The relationships between factor scores and documented CHD was determined by means of logistic regression analyses. Only Impulsive Anger-out correlated (positively) with CHD, but only when based on spouses' ratings and only in males (p < .01, RR = 3.13). Covarying traditional risk factors and cynicism did not attenuate this relationship. However, a significant relationship between Ho scale cynicism and CHD did not survive adjustment for traditional risk factors. Anxiety was not a risk factor for CHD.

Unlabelled: Surgical procedures usually involve the administration of narcotic drugs as anesthetics or adjuvants. To reverse the effects of anesthesia, opioid antagonists such as naloxone are commonly used. Due to its short lasting effects, patients receiving naloxone must be monitored carefully. Nalmefene, a pure opiate antagonist with a longer duration of action than naloxone, has shown promise in the reversal of opioid anesthesia., Methods: A simple dual-detector positron radiation detector system and [11C]carfentanil were used to compare the duration of blockade of cerebral mu opioid receptors by naloxone and nalmefene in eight normal volunteers. Carbon-11-carfentanil brain kinetics were monitored for 5 min and 2, 4, 8 and 24 hr after the administration of either nalmefene (1 mg or 1 microg/kg) or naloxone (2 mg or 2 microg/kg). Blood samples were obtained at the same times for plasma determinations., Results: Clearance half-times from opioid receptors were 28.7 +/- 5.9 hr for 1 mg of nalmefene and 2.0 +/- 1.6 hr for 2 mg of naloxone. Brain clearance times were about 21.1 and 3.4 times slower than plasma clearance times for nalmefene and naloxone, respectively., Conclusion: These findings suggest that the prolonged effects of nalmefene are related to the slow dissociation of nalmefene from opioid receptors, which are not reflected in the plasma curve. This longer blockade of opioid receptors by nalmefene represents an advantage in the clinical management of postsurgical reversal of narcotic anesthesia and opioid side effects as well as the reversal of opioid overdose.