Specific targeting of activated endothelium in rat adjuvant arthritis with a 99mTc-radiolabeled E-selectin-binding peptide.

OBJECTIVE: To determine the potential of an E-selectin-binding peptide (ESbp) to specifically bind activated endothelium in rheumatoid arthritis (RA) animal models. METHODS: ESbp (KYDGDITWDQLWDLMK; 2,027 daltons) was labeled with biotin and 99mTc. The affinity of ESbp derivatives for E-selectin was measured by enzyme-linked immunosorbent assay. The binding of biotin-ESbp was compared with that of an anti-E-selectin antibody, by immunohistochemical analyses of human synovial sections and sections from the Mycoplasma pulmonis MRL-lpr/lpr mouse arthritis model. 99mTc-ESbp was sequentially imaged in vivo with a gamma camera in the rat adjuvant-induced arthritis model. RESULTS: E-selectin expression was detected in human RA synovium and mouse arthritic synovium using biotin-ESbp. Both biotin-ESbp and 99mTc-labeled ESbp had high affinity for E-selectin (dissociation constant 2-5 nM). In vivo imaging showed specific binding of 99mTc-ESbp to the rat ankle joint prior to clinical manifestations of inflammation. CONCLUSION: These results demonstrate that activated endothelium can be targeted with 99mTc-ESbp. The specificity of targeting can be used to evaluate up-regulation of E-selectin in RA models, and to follow changes in this up-regulation during treatment trials.

59Fe is retained from an elemental 59Fe powder supplement without effects on 65Zinc, 47Calcium and 67Copper in young pigs.

In vivo counting with the use of a germanium detector evaluated the retention of an elemental 59Fe powder supplement while measuring potential interactions with zinc, calcium and copper. Effects of dietary iron and zinc on in vivo retentions of 59Fe, 65Zn, 67Cu and 47Ca were studied in young pigs. In Experiment 1, 4-d-old piglets fed a cereal-based diet were randomly assigned to one of four treatment groups (2 x 2 factorial arrangement, n = 5 per group). Variables were dietary iron source (either elemental iron or FeSO4, each at 100 mg iron/kg diet) and the dosage form of radioactive iron (either elemental 59Fe powder or 59FeSO4). Experiment 2 (2 x 3 factorial arrangement) was performed using two levels of iron (100 and 200 mg/kg, as elemental iron) and three levels of zinc (25, 50 and 100 mg/kg). Piglets were also dosed with 47Ca, 65Zn and 67Cu; all radioisotopes were measured for 8 d. Apparent absorption of elemental 59Fe powder was 13 +/- 1%, whereas 59Fe sulfate was significantly (P < 0.05) higher at 26 +/- 1%. The FeSO4 diet decreased 65Zn retention in Experiment 1, in contrast to the elemental iron diet, which did not have this effect in either experiment. Apparent 65Zn absorption averaged 44 +/- 2, 35 +/- 1 and 27 +/- 2% for the three levels of zinc (25, 50 and 100 mg/kg), respectively. Retention of 47Ca was not affected by dietary iron or zinc; retention of 67Cu was not affected by dietary iron. The data demonstrate good bioavailability of elemental iron without effects on zinc, copper and calcium.

Familial painful restless legs syndrome correlates with pain dependent variation of blood flow to the caudate, thalamus, and anterior cingulate gyrus.

To understand the relationship of caudate, thalamic, and anterior cingulate perfusion to pain states, we investigated familial restless legs syndrome in a father and daughter during the state of pain induced by immobility using semiquantitative regional cerebral blood flow (rCBF) brain single photon emission computed tomography (SPECT). The father underwent 4 brain SPECT scans using the rCBF tracer 99mTc-HMPAO several weeks apart, at different pain levels and after treatment with L-dopa. Caudate, thalamic, and anterior cingulate rCBF indices were measured. The caudate nuclei showed a 13% reduction in rCBF with increasing pain. The thalami and anterior cingulate showed a 7 and 6.6% increase in rCBF, respectively, with increasing pain. Compared to normal controls at rest, there was a decrease in caudate rCBF by 13% and an increase in thalamic rCBF by 3%. Linear regression for the caudate nuclei revealed a significant reduction in rCBF (p < 0.05), as pain increased. The daughter underwent an identical rCBF brain SPECT scan procedure at a high pain level induced by immobilization. Her scan showed a 12% reduction in caudate rCBF and a 1.2% increase in the anterior cingulate rCBF compared to healthy controls. The study supports the association between pain and decreased regional cerebral blood flow to the caudate nucleus as reported in fibromyalgia syndrome. There is increase in anterior cingulate rCBF with increasing pain. Our findings also corroborate that there is increased thalamic rCBF with pain stimulation.

Tc-99m HMPAO brain SPECT scanning in Munchausen syndrome.

Regional cerebral blood flow was studied in a patient with Munchausen syndrome using high resolution Tc-99m HMPAO SPECT. The scan demonstrated marked hyperperfusion of the right hemithalamus. The cranial CT scan was normal. The abnormal right hemithalamic blood flow is discussed in relation to the hypothesized neuropathy of this disorder.

Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels.

OBJECTIVE: To determine if regional cerebral blood flow (rCBF) in the left and right hemithalami or the left and right heads of the caudate nucleus is abnormal in women with fibromyalgia (FM). METHODS: Resting-state rCBF in the hemithalami and left and right heads of the caudate nucleus of 10 untreated women with FM and 7 normal control women was measured by single-photon-emission computed tomography. Pain threshold levels at tender and control points also were assessed in both the women with FM and the controls. RESULTS: The rCBF in the left and right hemithalami and the left and right heads of the caudate nucleus was significantly lower in women with FM than in normal controls (P = 0.01, P = 0.003, P = 0.01, and P = 0.02, respectively). Compared with controls, the women with FM also were characterized by significantly lower cortical rCBF (P = 0.001) and lower pain threshold levels at both tender points (P = 0.0001) and control points (P = 0.0001). CONCLUSION: The findings of low rCBF and generalized low pain thresholds support the hypothesis that abnormal pain perception in women with FM may result from a functional abnormality within the central nervous system.

Validation of a reference method for correlation of anatomic and functional brain images.

We describe a reference device that provides accurate correlations between anatomic and functional brain images. The reference device, which generates fiduciary reference points on sequential scan planes, is positioned adjacent to the orbitomeatal line of the subject, and held in place by a framework anchored to the external auditory meatus. The reference system was tested on 17 subjects undergoing Tc-99m-hexamethylpropyleneamine oxime (Tc-99m-HM-PAO) brain single photon emission computed tomography (SPECT) and cranial computed tomography (CT) scans. The centers of the caudate nuclei, thalami, brain stem, and cerebellar vermis were identified independently on CT and SPECT. The average difference +/- 1 sd between structure locations (x, y, and z) on SPECT and CT were calculated as 1.86 +/- 1.5, 2.16 +/- 1.4, and 1.83 +/- 1.9 mm, respectively. The relevance of the method to clinical applications is illustrated by the localization of a recurrent viable glioma and an epileptogenic focus. This reference system provides an accurate, rapid, and noninvasive patient-specific method for the correlation of brain structure with brain function.

Pathological lying associated with thalamic dysfunction demonstrated by [99mTc]HMPAO SPECT.

The authors report a case in which pathological lying is associated with right hemithalamic dysfunction as shown by [99mTc]HMPAO SPECT brain scanning. This association has not been demonstrated previously and is noteworthy because it supports the hypothesized roles of the thalamus and associated brain regions in the modulation of behavior and cognition.

Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder.

This article is intended to elucidate some of the neuropathogenetic mechanisms possibly operative in obsessive-compulsive disorder (OCD). Relevant literature is reviewed, with attention to psychologic, and pathologic considerations. Anatomy, neurochemistry, and known functional associations with neuropathological and behavioral abnormalities of implicated brain regions are discussed. The authors propose that dysfunction of neuronal circuits interconnecting the orbitofrontal cortex, basal ganglia/limbic striatum, and thalamus serves a critical role in the pathogenesis of OCD and that obsessive-compulsive symptoms occur when an aberrant positive feedback loop develops in the reciprocally excitatory frontothalamic neuronal interchange, which is inadequately integrated or inhibited by the ventromedial (limbic) portions of the striatum; the ventromedial striatum may serve to modulate activity in the frontothalamic circuit through a negative feedback loop.