Long-term estrogen therapy and 5-HT(2A) receptor binding in postmenopausal women; a single photon emission tomography (SPET) study.

Variation in estrogen level is reported by some to affect brain maturation and memory. The neurobiological basis for this may include modulation of the serotonergic system. No neuroimaging studies have directly examined the effect of extended estrogen therapy (ET), on the 5-HT(2A) receptor in human brain. We investigated the effect of long-term ET on cortical 5-HT(2A) receptor availability in postmenopausal women. In a cross-sectional study, we compared cortical 5-HT(2A) receptor availability in 17 postmenopausal ERT-naive women and 17 long-term oophorectomised estrogen-users, age- and IQ-matched using single photon emission tomography and the selective 5-HT(2A) receptor ligand (123)I-5-I-R91150. Also, we used the Revised Wechsler Memory Scale to relate memory function to 5-HT(2A) receptor availability. Never-users had significantly higher 5-HT(2A) receptor availability than estrogen-users in hippocampus (1.17 vs. 1.11, respectively, p=0.02), although this did not remain significant after correction for multiple comparisons. Hippocampal 5-HT(2A) receptor availability correlated negatively with verbal and general memory and delayed recall (r=-0.45, p=0.01; r=-0.40, p=0.02; r=-0.36, p=0.04). Right superior temporal 5-HT(2A) receptor availability correlated negatively with verbal memory (r=-0.36, p=0.04). In estrogen-users, receptor availability correlated negatively with verbal and general memory (r=-0.70, p=0.002; r=-0.69, p=0.002); and in never-users, receptor availability negatively correlated with attention and concentration (r=-0.54, p=0.02). Long-term ET may be associated with lower 5-HT(2A) receptor availability in hippocampus. This may reflect increased activity within the serotonergic pathway leading to down-regulation of post-synaptic receptor. Also, increased availability of the 5-HT(2A) receptor in hippocampus is associated with poorer memory function.

Nuclear imaging is more sensitive for the detection of viable myocardium than dobutamine echocardiography.

Intact perfusion, preserved metabolism of free fatty acids and glucose, and the presence of contractile reserve have been used as markers of viable myocardium. However, not all viable myocardium may exhibit all these characteristics. Accordingly, these features were evaluated in patients with chronic coronary artery disease and left ventricular dysfunction. Fourteen patients with chronic ischaemic heart disease and depressed left ventricular function (LVEF 34+/-10%) perfusion was evaluated by early resting 201Tl single photon emission computed tomography (SPECT), fatty acid utilization by 15-p-[123I]iodophenyl-3-(R,S)-methylpentadecanoic acid SPECT, glucose utilization by 2-[18F]fluoro-2-deoxy-D-glucose SPECT and contractile reserve (CR) by dobutamine echocardiography. The comparison of the different modalities was restricted to akinetic or dyskinetic myocardium as assessed by resting 2-dimensional echocardiography. For all techniques a 13-segment model was used. Sixty-four of 182 segments (35%) showed akinesia or dyskinesia. Intact perfusion was found in 33/64 (52%) segments. Fatty acid utilization was maintained in 38/64 (59%) segments and glucose utilization was maintained in 38/64 (59%) segments. CR was present in significantly fewer segments: 21 of 64 (33%) (P<0.01 vs glucose and fatty acid utilization). In the 21 segments with preserved CR, perfusion was intact in 16/21 (76%) segments, fatty acid utilization in 19/21 (90%) segments and glucose utilization was preserved in all (100%) segments. Conversely, in the 43 segments without CR, 17 segments (40%) showed intact perfusion, 19 segments (44%) preserved fatty acid utilization and 17 (40%) still showed preserved glucose utilization. Disagreement in segments between the viability markers was caused mainly by segments without CR but preserved perfusion, fatty acid or glucose utilization. The substantial number of segments with preserved glucose and fatty acid utilization but without contractile reserve, suggests an underestimation of myocardial viability by dobutamine echocardiography.

Adsorption of radioiodine on platinum: a fast and simple column method to obtain concentrated and pure radioiodide in either water or anhydrous solvents.

Radioiodine can be adsorbed on a small column filled with platinum powder from an acidified aqueous solution. The adsorption is nearly quantitative, irrespective of the oxidation state of the iodine used. With an alternated flow of hydrogen gas and solvent, the iodine can be desorbed from the platinum into an aqueous or organic solvent. Depending on the solvent used, the desorption process is also nearly quantitative, and the eluate obtained contains almost pure radioiodide. Using this method, labelling reactions with radioiodide are no longer restricted to water-stable substrates and catalysts.

Increased uptake of iodine-123-BMIPP in chronic ischemic heart disease: comparison with fluorine-18-FDG SPECT.

UNLABELLED: To evaluate the potential role of 15-p-[123I]iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP) for the assessment of myocardial viability, the patterns of BMIPP versus 18F-fluorodeoxyglucose (FDG) uptake were evaluated in patients with chronic ischemic heart disease. METHODS: Twenty-one patients with stable chronic coronary artery disease underwent resting TI SPECT to delineate myocardial perfusion followed by FDG SPECT to detect residual viability in regions showing perfusion defects. Resting BMIPP SPECT was obtained on a separate day. SPECT images were displayed as polar maps (13 segments) and analyzed semiquantitatively. A total of 273 segments were analyzed. RESULTS: In 87 (32%) of the segments, a perfusion defect was observed. In perfusion defects, the distributions of BMIPP/TI (mis)matches were significantly different (p < 0.0001) between the FDG viable (n = 42) and nonviable (n = 45) segments. A BMIPP/TI mismatch (BMIPP uptake higher than perfusion) was found in 74% of FDG viable segments, whereas a BMIPP/TI match (BMIPP uptake equal or lower than perfusion) was found in 69% of FDG nonviable segments. Agreement between matching or mismatching of segments was assessed to be 71%. Agreement was 81% when the data were analyzed on a patient basis. The observed frequency of BMIPP/TI mismatches was significantly higher (p < 0.05) in segments with an old myocardial infarction (20 of 36; 55%) than it was in subacute infarcted myocardium (5 of 21; 24%). CONCLUSION: In chronically hypoperfused myocardium, an increased BMIPP uptake relative to perfusion was detected, which is different from the decreased BMIPP uptake often reported in (sub)acute myocardial ischemia. Therefore, the interval from infarction may be an important factor in the interpretation of BMIPP scintigraphic data. Increased BMIPP uptake was associated with FDG/TI mismatches and may, therefore, confirm myocardial viability. Some segments with a FDG/TI mismatch, however, revealed a BMIPP/TI match. These segments may contain viable but more severely damaged tissue. Further studies on functional recovery are warranted to assess the significance of a BMIPP/perfusion (mis)match for tissue viability.

Evaluation of heart-to-organ ratios of 123I-BMIPP and the dimethyl-substituted 123I-DMIPP fatty acid analogue in humans.

Radioiodinated fatty acid analogues modified by methyl-substitution are used for single photon emission tomography (SPET) imaging of the heart. The effect of mono- and dimethyl-substitution on heart-to-organ ratios was investigated in humans to evaluate their relative merits for SPET image quality. Planar total body scans were performed in fasting patients with coronary artery disease, but without heart failure, 1 h after administration of 111 MBq 15-(p-[I-123]-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP, n = 7) or 111 MBq 15-(p-[I-123]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP, n = 4). Because these branched fatty acids are used for cardiac imaging, we focused on heart-to-organ (heart/organ) ratios by comparing small regions of interest in heart, liver, lung, muscle and bladder. Both tracers showed good visualization of the heart. DMIPP showed a relatively high liver uptake: the heart/liver ratios for DMIPP and BMIPP were 0.39 +/- 0.05 and 1.00 +/- 0.12, respectively (P < 0.0001). Increased lung activity was found for BMIPP, with a heart/lung ratio of 1.63 +/- 0.17 versus 2.32 +/- 0.28 for DMIPP (P < 0.001). In contrast to DMIPP, BMIPP also showed increased activity in the bladder. In conclusion, BMIPP and DMIPP show different distribution patterns. Despite the more favourable heart/lung ratios for DMIPP, the high liver uptake affects cardiac SPET image quality and therefore BMIPP appears to provide superior cardiac SPET image quality in humans.

A simple and efficient method to remove free radioiodide from *I-radiopharmaceuticals.

Removal of free radioiodide from *I-radiopharmaceuticals was easily performed by using a pure metallic silver membrane, placed in a screwable holder. Well-known radiopharmaceuticals such as 3-iodobenzylguanidine, Hippuran, iomazenil and fatty acids were treated successfully, and gave reproducible results. Only a trace of free radioiodide (< or = 1%) was left after passing the silver membrane, while rest activity due to retention of the radiopharmaceutical on the membrane was negligible (2%-5%). This simple and reliable method offers the possibility of application as a last purification step in routine productions, in research or in a nuclear medicine department's pharmacy.

New fast preparation of 123I labelled radiopharmaceuticals.

A new fast kit preparation of 123I labelled radiopharmaceuticals such as IMP, HIPDM, MIBG and Hippuran is proposed. A radiochemical yield greater than 99% is obtained at 100 degrees C within 10-30 min. The new labelling procedure is based on the nucleophilic exchange in presence of Cu(I) and an excess of reducing agents. The four kit prepared 123I-radiopharmaceuticals have been used with success in clinical studies involving 400 patients. The proposed method is also compared with earlier described methods which, yielding labelled side products and 123I2, do not fulfill the requirements for kit labelling.

New high yield Cu(I) assisted 123I radioiodination of 15(p-I-phenyl)-9-methyl pentadecanoic acid, a potential myocardial tracer.

A new high yield 123I radioiodination (97%), based on the Cu(I) assisted isotopic exchange in an ethanol water mixture, of 15(p-I-phenyl)-9 methyl pentadecanoic acid, a potential myocardial tracer, is proposed. The method allows a true kit preparation of radioiodinated phenyl fatty acids for a substrate concentration of +/- 10(-6) moles. High specific activities (greater than 0.1 mCi/micrograms) can be obtained when coupling the labelling method to HPLC purification with an overall radiochemical yield of 75%.