A computational model of neurodegeneration in Alzheimer's disease.

Disruption of mental functions in Alzheimer's disease (AD) and related disorders is accompanied by selective degeneration of brain regions. These regions comprise large-scale ensembles of cells organized into systems for mental functioning, however the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and functional systems is not clear. Here we present a model of the association between dementia symptoms and degenerative brain anatomy using F18-fluorodeoxyglucose PET and dimensionality reduction techniques in two cohorts of patients with AD. This reflected a simple information processing-based functional description of macroscale brain anatomy which we link to AD physiology, functional networks, and mental abilities. We further apply the model to normal aging and seven degenerative diseases of mental functions. We propose a global information processing model for mental functions that links neuroanatomy, cognitive neuroscience and clinical neurology.

Tau uptake in agrammatic primary progressive aphasia with and without apraxia of speech.

BACKGROUND AND PURPOSE: The non-fluent/agrammatic variant of primary progressive aphasia (agPPA) is a heterogeneous diagnosis wherein some individuals have apraxia of speech (AOS). When agPPA includes AOS, a tauopathy is the likely underlying pathology. Recently, [18F]AV-1451 was developed for the in-vivo assessment of tau. In this study, we compared patterns of tau tracer uptake in patients with agPPA with and without AOS. METHODS: Nine patients with agPPA (four without AOS) underwent tau positron emission tomography imaging with [18F]AV-1451. Uptake of [18F]AV-1451 was assessed as cortical to cerebellar crus ratio (standard uptake value ratio) in cortical regions of interest measured using the MCALT atlas and compared voxel-wise in SPM12. Each patient was age- and sex-matched to three controls. RESULTS: The agPPA without AOS showed uptake in the left frontal and temporal lobes, whereas agPPA with AOS showed uptake in the bilateral supplementary motor areas, frontal lobes, precuneus and precentral gyrus relative to controls. The left precentral gyrus had uptake in agPPA with AOS relative to those without AOS. CONCLUSIONS: This cross-sectional study suggests that [18F]AV-1451 uptake in the precentral gyrus is implicated in AOS in agPPA.

[18F] AV-1451 uptake in corticobasal syndrome: the influence of beta-amyloid and clinical presentation.

Corticobasal syndrome (CBS) is a phenotypic manifestation of diverse pathologies, including Alzheimer's disease and 4-repeat tauopathies. Predicting pathology in CBS is unreliable and, hence, molecular neuroimaging may prove to be useful. The aim of this study was to assess regional patterns of uptake on [18F] AV-1451 PET in CBS and determine whether patterns of uptake differ according to beta-amyloid deposition or differing clinical presentations. Fourteen patients meeting criteria for CBS underwent Pittsburgh Compound B (PiB) and [18F] AV-1451 PET. Seven patients presented as CBS and seven presented with apraxia of speech (AOS) and later evolved into CBS. A global PiB summary was calculated and used to classify patients as PiB (-) or PiB (+). AV-1451 uptake was calculated in fourteen regions-of-interest, with values divided by uptake in cerebellar crus grey matter to generate standard uptake value ratios. AV-1451 uptake was considered elevated if it fell above the 95th percentile from a group of 476 cognitively unimpaired normal controls. Six of the 14 CBS patients (43%) were PiB (+), with three of these patients showing strikingly elevated AV-1451 uptake across many cortical regions. Of the eight PiB (-) patients, only those with AOS showed elevated AV-1451 uptake in supplementary motor area and precentral cortex compared to controls. No region of elevated AV-1451 uptake were observed in PiB (-) typical CBS patients without AOS. These results suggest that regional [18F] AV-1451 is variable in CBS and depends on the presence of beta-amyloid as well as clinical presentation such as AOS. PiB (+) CBS does not necessarily reflect underlying Alzheimer's disease; however, the possibility some of these patients will evolve into Alzheimer's disease over time cannot be excluded.

Phase I trial of systemic administration of Edmonston strain of measles virus genetically engineered to express the sodium iodide symporter in patients with recurrent or refractory multiple myeloma.

MV-NIS is an Edmonston lineage oncolytic measles virus expressing the human sodium iodide symporter-a means for monitoring by non-invasive imaging of radioiodine. Patients with relapsed, refractory myeloma who had explored all other treatment options were eligible for this Phase I trial. Cohort 1 was treated with intravenous MV-NIS, and Cohort 2 received cyclophosphamide 2 days prior to MV-NIS. Thirty-two patients were treated. Cohort 1 initially enrolled to four dose levels without reaching maximum tolerated dose (MTD) and subsequently to two higher dose levels when improved virus manufacture technology made it possible. MTD was not reached in Cohort 1, and TCID50 1011 is the dose being used in a Phase II trial of single agent MV-NIS. Grade 3-4 adverse events in both cohorts at all dose levels were: neutropenia (n=9); leukocyte count decreased (n=5); thrombocytopenia (n=2); and CD4 lymphocytes decreased, anemia and lymphopenia (each n=1). MV-N RNA sequences were amplified from gargle specimens, blood and urine. 123I scans were positive in eight patients. One patient achieved a complete response; transient drops in serum free light chains were seen in other patients. MV-NIS is capable of replicating before being cleared by the immune system. Oncolytic viruses offer a promising new modality for the targeted infection and destruction of disseminated myeloma.

Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

BACKGROUND AND OBJECTIVES: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. METHODS AND RESULTS: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. CONCLUSIONS: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.

Regional ß-amyloid burden does not correlate with cognitive or language deficits in Alzheimer's disease presenting as aphasia.

BACKGROUND AND PURPOSE: A subset of patients with Alzheimer's disease (AD) present with early and prominent language impairment (aphasic AD). Our previous study demonstrated an association between global ß-amyloid burden measured on [(11)C] Pittsburgh compound B (PiB) positron emission tomography and general cognitive impairment, but not with aphasia, in such subjects. As a follow-up, whether there is any association between regional ß-amyloid burden, atrophy on magnetic resonance imaging (MRI) and global cognitive impairment, aphasia or other cognitive and functional impairment in aphasic AD is assessed. METHODS: Forty-four aphasic AD subjects who underwent PiB scanning and volumetric MRI and were determined to be positive for ß-amyloid deposition were analyzed. All had completed detailed neurological, neuropsychological and language batteries. Spearman's rank-order correlation was utilized to assess for associations. RESULTS: Greater visuospatial impairment was associated with increased ß-amyloid burden in the primary visual cortex (P = 0.001). Although there were many trends for associations between neurocognitive and language deficits and regional ß-amyloid burden, there were no strong associations that survived correction for multiple comparisons. However, neurocognitive and language impairment in these subjects strongly correlated with the degree of left lateral temporal and inferior parietal atrophy (P < 0.004). CONCLUSIONS: The findings from this study suggest a close relation between the severity of regional atrophy and cognitive and language impairment, but argue against a strong association between regional ß-amyloid burden and such deficits in aphasic AD subjects. Hence, other pathological factors may be driving the previously identified association between global ß-amyloid deposition and general cognitive impairment in aphasic AD.

Early detection of prostate cancer relapse by biochemistry and diagnostic imaging.

Prostate cancer (PCa) is a common malignancy in men associated with an increase in the incidence rate. Radical prostatectomy (RP) or external beam radiotherapy (EBRT) represents the most employed treatments for the local control of disease. However, 10-50% of patients who experienced a recurrence of disease after primary treatments can benefit from salvage or palliative therapies. To date, prostate specific antigen (PSA) is usually used in clinical practice to monitor the status of disease and to early detect the recurrence of PCa. Nevertheless, PSA cannot discriminate the presence of local vs. distant metastatic disease. Circulating tumor cells are considered as a sign of disease widespread, but their correlation with metastatic PCa and local recurrence of disease is still indeterminate. Digital rectal exploration and transrectal ultrasonography are considered the first clinical and diagnostic approach to identify the local recurrence of PCa, but are associated with a low detection rate and low diagnostic accuracies. Conversely, magnetic resonance imaging (MRI) has gained a great importance in this setting of disease, being able to determine the presence of local recurrence with high sensitivity, also in the presence of low serum PSA levels. Lastly, the introduction of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline agents let to improve the management of patients with early recurrence of disease, although its accuracy is linked to the PSA and PSA dynamic values. New radiopharmaceutical agents, like 68Ga-PSMA or 18F-FACBC and others could improve the diagnostic accuracy of PET/CT, but the data is still preliminary. In the present review we will discuss both clinical and diagnostic instrumentations, actually available in clinical practice, able to early identify the presence of recurrent PCa and to differentiate between local and distant relapse of tumor.

Oncologic PET/CT interpretation and reporting approaches. Survey in clinical practice.

AIM: To elucidate techniques most commonly used for interpreting oncologic PET/CT studies. This survey forms a basis to work on standardization of reporting and highlight the most important issues to be addressed. METHODS: A web-based survey of 329 PET/CT imaging specialists was designed with the intent to determine image interpretation patterns. The questionnaire consisted of 19 questions. Of the 329 participants, 230 were nuclear medicine specialists, 46 were radiologists, and 53 had dual-board certification. RESULTS: Report ofstandardized uptake values (SUV) is not consistent;only50.2% of respondents always report SUVs, while 45.2% report only if needed or requested. 80.9% of respondents indicated that reporting of SUV is only appropriate when its limitations are understood whereby a large majority prefer to report SUVmax. Maximum intensity projection (MIP) images are almost always reviewed by 91.1% of the respondents. An accurate and detailed clinical history is considered an essential element for reading PET/CT studies by 84.0%, but only 20.7% report that this is always available. The most common self-reported average time for reviewing and reporting of whole body PET/CT (with no prior comparison scan) was 15-20 min (27.5%). CONCLUSION: PET readers have considerable reservations regarding the use and reporting of SUVs. SUVmax is more frequently used than SUVmean. Evaluation of MIP images is considered an important element of PET/CT interpretation. Although availability of sufficient patient's history is considered essential, this is rarely available.

Amyloid burden correlates with cognitive decline in Alzheimer's disease presenting with aphasia.

BACKGROUND AND PURPOSE: A subset of patients with Alzheimer's disease (AD) present with early and prominent language deficits. It is unclear whether the burden of underlying ß-amyloid pathology is associated with language or general cognitive impairment in these subjects. METHODS: The relationship between cortical ß-amyloid burden on [(11) C]Pittsburgh compound B (PiB) positron emission tomography (PET) and performance on the Montreal Cognitive Assessment (MoCA), the Wechsler Memory Scale - Third Edition (WMS-III), the Boston Naming Test (BNT) and the Western Aphasia Battery (WAB) was assessed using regression and correlation analyses in subjects presenting with aphasia who showed ß-amyloid deposition on PiB PET. RESULTS: The global PiB ratio was inversely correlated with MoCA (P = 0.02) and the WMS-III Visual Reproduction (VR) subtest (VR I, P = 0.02; VR II, P = 0.04). However, the correlations between PiB ratio, BNT (P = 0.13), WAB aphasia quotient (P = 0.11) and WAB repetition scores (P = 0.34) were not significant. CONCLUSION: This study demonstrates that an increased cortical ß-amyloid burden is associated with cognitive impairment, but not language deficits, in AD subjects presenting with aphasia. The results suggest that ß-amyloid deposition could be partly contributing to impaired cognition in such patients whilst language dysfunction may be more influenced by other pathological mechanisms, perhaps downstream pathways of ß-amyloid deposition.

Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease.

OBJECTIVE: Recommendations for the diagnosis of preclinical Alzheimer disease (AD) have been formulated by a workgroup of the National Institute on Aging and Alzheimer's Association. Three stages of preclinical AD were described. Stage 1 is characterized by abnormal levels of ß-amyloid. Stage 2 represents abnormal levels of ß-amyloid and evidence of brain neurodegeneration. Stage 3 includes the features of stage 2 plus subtle cognitive changes. Stage 0, not explicitly defined in the criteria, represents subjects with normal biomarkers and normal cognition. The ability of the recommended criteria to predict progression to cognitive impairment is the crux of their validity. METHODS: Using previously developed operational definitions of the 3 stages of preclinical AD, we examined the outcomes of subjects from the Mayo Clinic Study of Aging diagnosed as cognitively normal who underwent brain MRI or [(18)F]fluorodeoxyglucose and Pittsburgh compound B PET, had global cognitive test scores, and were followed for at least 1 year. RESULTS: Of the 296 initially normal subjects, 31 (10%) progressed to a diagnosis of mild cognitive impairment (MCI) or dementia (27 amnestic MCI, 2 nonamnestic MCI, and 2 non-AD dementias) within 1 year. The proportion of subjects who progressed to MCI or dementia increased with advancing stage (stage 0, 5%; stage 1, 11%; stage 2, 21%; stage 3, 43%; test for trend, p < 0.001). CONCLUSIONS: Despite the short follow-up period, our operationalization of the new preclinical AD recommendations confirmed that advancing preclinical stage led to higher proportions of subjects who progressed to MCI or dementia.

Similar clinical and neuroimaging features in monozygotic twin pair with mutation in progranulin.

OBJECTIVE: To report the phenotypic characterization of monozygotic twins with mutations encoding progranulin (PGRN). METHODS: We studied a twin pair with an exon 4 gene deletion in the PGRN gene. Both twins had clinical and neuropsychological examinations as well as structural MRI and fluorodeoxyglucose PET (FDG-PET) scans. PGRN gene sequencing was performed followed by progranulin ELISA in plasma. RESULTS: Both twins manifested symptoms within 3 years of each other, with early behavioral, language, dysexecutive, and memory problems. MRI and FDG-PET imaging demonstrated a strikingly similar topography of findings with clear left hemisphere predominance. Serum progranulin levels in both were well below those from a normal population sample. CONCLUSIONS: Compared with the heterogeneity seen in many families with PGRN mutations, these monozygotic twins demonstrated strong clinical, neuroimaging, and serum progranulin level similarities, demonstrating the importance of shared genetic profiles beyond environmental influences in the symptomatic expression of the disease.

APOE modifies the association between Aß load and cognition in cognitively normal older adults.

OBJECTIVE: To determine the relationship between ß-amyloid (Aß) load as measured by [(11)C]-Pittsburgh compound B (PiB) PET and cognitive function in cognitively normal older adults. METHODS: We studied 408 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging (MCSA) from January 2009 through March 2011. The participants underwent PiB PET and neuropsychometric testing within 6 months. The association between PiB retention and cognitive function was measured by partial correlation and an interaction with APOE status was tested using linear regression after adjusting for age, sex, and education. RESULTS: Higher PiB retention was associated with cognitive performance (Spearman partial r = -0.18; p < 0.01), specifically the memory, language, attention/executive, and visual-spatial processing domains in the whole group of participants. The association between PiB retention and cognition was modified by the APOE status on linear regression analysis even after controlling for the differences in the distribution of PiB values among APOE ε4 carriers and noncarriers (p = 0.02). Cognitive performance was associated with the Aß deposition in the frontal, temporal, and parietal lobe association cortices in APOE ε4 carriers on SPM analysis (p < 0.001). CONCLUSION: There is a modest association between PiB retention and cognitive function in cognitively normal older adults and this relationship between Aß load and cognitive function is modified by APOE status. Whereas Aß load is associated with greater cognitive impairment in APOE ε4 carriers, the cognitive function in APOE ε4 noncarriers is influenced less by the Aß load, suggesting that APOE isoforms modulate the harmful effects of Aß on cognitive function.

Magnetic resonance spectroscopy, ß-amyloid load, and cognition in a population-based sample of cognitively normal older adults.

OBJECTIVE: To determine the relationship between proton magnetic resonance spectroscopy ((1)H MRS) metabolites and ß-amyloid (Aß) load and the effects of Aß load on the association between (1)H MRS metabolites and cognitive function in cognitively normal older adults. METHODS: We studied 311 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging from January 2009 through September 2010. Participants underwent (11)C-Pittsburgh compound B (PiB) PET, (1)H MRS from the posterior cingulate gyri, and neuropsychometric testing to assess memory, attention/executive, language, and visual-spatial domain functions within 6 months. Partial Spearman rank order correlations were adjusted for age, sex, and education. RESULTS: Higher PiB retention was associated with abnormal elevations in myoinositol (mI)/creatine (Cr) (partial r(s) = 0.17; p = 0.003) and choline (Cho)/Cr (partial r(s) = 0.13; p = 0.022) ratios. Higher Cho/Cr was associated with worse performance on Auditory Verbal Learning Test Delayed Recall (partial r(s) = -0.12; p = 0.04), Trail Making Test Part B (partial r(s) = 0.12; p = 0.04), Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol (partial r(s) = -0.18; p < 0.01), and WAIS-R Block Design (partial r(s) = -0.12; p = 0.03). Associations between (1)H MRS metabolites and cognitive function were not different among participants with high vs low PiB retention. CONCLUSION: In cognitively normal older adults, the (1)H MRS metabolite ratios mI/Cr and Cho/Cr are associated with the preclinical pathologic processes in the Alzheimer disease cascade. Higher Cho/Cr is associated with worse performance on domain-specific cognitive tests independent of Aß load, suggesting that Cho/Cr elevation may also be dependent on other preclinical dementia pathologies characterized by Cho/Cr elevation such as Lewy body or ischemic vascular disease in addition to Aß load.

Effects of age on the glucose metabolic changes in mild cognitive impairment.

BACKGROUND AND PURPOSE: Decreased glucose metabolism in the temporal and parietal lobes on FDG-PET is recognized as an early imaging marker for the AD pathology. Our objective was to investigate the effects of age on FDG-PET findings in aMCI. MATERIALS AND METHODS: Twenty-five patients with aMCI at 55-86 years of age (median = 73 years) and 25 age- and sex-matched CN subjects underwent FDG-PET. SPM5 was used to compare the FDG uptake in patients in aMCI-old (>73 years) and aMCI-young (

Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan.

OBJECTIVES: Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis. METHODS: EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard. RESULTS: The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis. CONCLUSION: FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.

Biodistribution and dosimetry of [(18)F]fluorodeoxyglucose labelled leukocytes in normal human subjects.

SUMMARY: This study was performed in order to assess [(18)F]fluorodeoxyglucose white blood cell ((18)F-FDG WBC) dosimetry in normal human subjects. Using previously reported methods, mixed cell suspensions of autologous leukocytes were prepared from four normal volunteers. Leukocytes were labelled in heparin-saline by incubation with (18)F-FDG at 37 degrees C for 20 min. After washing and resuspension, (18)F-FDG WBCs (225-315 MBq) were administered by intravenous injection. Whole-body imaging was performed at 0.5, 1, 2, 4 and 6 h using a GE Varicam with 511 keV collimation. Blood samples were obtained at corresponding times as well as fractionated urinary collection. Whole-body anterior and posterior images were used for calculation of organ dosimetry. Uptake of (18)F-FDG WBCs occurred predominantly within the reticulo-endothelial system. Plasma activity, urinary excretion (9.9+/-2.3% at 6 h), and brain uptake (1.7+/-0.4%) were consistent with partial elution of (18)F-FDG. Positron emission tomography imaging performed at 5-6 h after injection yielded good quality images of reticulo-endothelial uptake. Whole-body and organ dosimetry for (18)F-FDG WBCs in doses of 225-250 MBq are comparable with reported results for conventional doses of (111)In oxine labelled leukocytes. Further studies of (18)F-FDG WBC as an agent for positron emission tomography imaging of inflammatory disease appear warranted.

The cost-effectiveness of fluorodeoxyglucose 18-F positron emission tomography in the N0 neck.

BACKGROUND: Although surgery and radiation are effective treatments of regional lymphatics for classification N0 head and neck squamous cell carcinoma (HNSCC) patients, both have morbidities that could be avoided in approximately 70% of patients without lymph node disease with better diagnostic information. 18-F fluoro-2-deoxyglucose positron emission tomography (FDG-PET) has shown promise in detecting subclinical lymph node disease, but its cost and availability have limited its use. Here, we sought to determine whether the use of FDG-PET was cost-effective as part of a treatment strategy for classification N0 HNSCC patients. METHODS: The cost-effectiveness of proceeding from classification of N0 by computed tomography to a PET scan was estimated using standard methods of economic evaluation. Costs were for a large, Midwestern university medical center. Probabilities were computed from a review of the literature. Utilities were obtained by a time-tradeoff method, and life expectancy was estimated using the Surveillance, Epidemiology, and End Results database. Outcomes measures were cost per year of life saved and cost per quality-adjusted life-year. RESULTS: Modified radical neck dissection was associated with the lowest morbidity (utility [u] = 0.93), and radical neck dissection plus radiation was associated with the highest (u = 0.68). Life expectancy was estimated to be 5.9 and 11.5 years for patients with and without lymph node disease, respectively. The incremental cost-effectiveness ratio for the PET strategy was $8718 per year of life saved, or $2505 per quality-adjusted life-year. CONCLUSIONS: A diagnostic and treatment strategy that proceeds from classification of N0 to a PET scan is cost-effective. Prospective studies that evaluate this strategy are important to assure that these simulation results are realized in clinical practice.

The use of lymphoscintigraphy and PET in the management of head and neck melanoma.

OBJECTIVES: Lymphoscintigraphy with sentinel node dissection and 18 fluoro-2-deoxyglucose positron emission tomography (PET) are being used independently in the management of many intermediate and thick melanomas of the head and neck. We report a series of patients with melanoma of the head and neck with Breslow depths greater than 1.0 mm and clinically negative regional nodes that were evaluated prospectively with PET and lymphoscintigraphy. STUDY DESIGN AND SETTING: Between July 1, 1998 and December 30, 2000 PET scans were obtained preoperatively on 18 patients undergoing resection of head and neck melanoma. Lymphoscintigraphy and sentinel node dissection was performed. Resection of the primary lesion was then carried out with adequate margins and the defects were reconstructed. RESULTS: Sentinel node(s) were found in 17/18 patients (94.4%); 5/18 (27.8%) of cases had metastases. PET detected nodal metastasis preoperatively in 3 patients (16.7%), one of which had a positive sentinel node dissection. CONCLUSION: PET and lymphoscintigraphy offer complimentary ways of evaluation for metastatic melanoma.

18F-FDG labelling of human leukocytes.

Radiolabelled leukocytes are useful for the imaging of inflammation and infection, and 18F-fluorodeoxyglucose (18F-FDG) is known to concentrate in metabolically active cells. We evaluated the feasibility of leukocyte labelling with 18F-FDG using ACD and heparin anticoagulants at 20 degrees C and 37 degrees C, with and without gentle mixing during incubation. With leukocytes (WBC) harvested from 20 ml blood, studies were performed using 18F-FDG in concentrations of 3.7-74 MBq (0.1-2.0 mCi). 18F-FDG WBC stability in platelet-poor plasma was assessed at 1-4 h. Satisfactory labelling efficiency was achieved with incubation in heparin-saline at 37 degrees C for 30 min (62.7+/-1.6%), and was further enhanced by mixing during incubation (78.1+/-3.9%). Cell labelling was predominantly of granulocytes (78.5+/-1.4%). 18F-FDG WBC was relatively stable in platelet-poor plasma for up to 4 h, and no cell staining was observed in viability studies using trypan blue. These results indicate the feasibility of leukocyte labelling with 18F-FDG, providing an approach that may be useful in PET imaging of inflammation and infection.