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J R Ballinger

Publications and source records attributed to J R Ballinger.

At least 37 records · Page 2Linked to original sources
PubMed2000

In vitro comparison of sestamibi, tetrofosmin, and furifosmin as agents for functional imaging of multidrug resistance in tumors.

Sestamibi, tetrofosmin, and furifosmin are 99mTc-labeled myocardial perfusion imaging agents which have been shown to be substrates for P-glycoprotein (Pgp), the multidrug-resistance transporter which is overexpressed in some tumors. The three tracers were directly compared in vitro in the human breast cancer cell line MCF7-WT and two multidrug-resistant variants, MCF7-BC19 (MDR1 gene transfected) and MCF7-AdrR (doxorubicin selected). Tracer accumulation over the course of 60 minutes was determined. Dose-response curves were generated for two modulators of Pgp function, GG918 and PSC833. The general shape of accumulation curves for the three tracers in MCF7-WT cells was similar, with accumulation levels being sestamibi > tetrofosmin > furifosmin. Accumulation of sestamibi and furifosmin in MCF7-BC19 cells was reduced to 10% and 21% of MCF7-WT levels, respectively, but this accumulation deficit could be completely reversed by addition of 0.1 microM GG918 or 2 microM PSC833. Accumulation of sestamibi and tetrofosmin in MCF7-AdrR cells was 1.6% and 12% of MCF7-WT levels, respectively, and could only be enhanced to 30% and 45% of MCF7-WT levels by addition of GG918 or PSC833. In contrast, furifosmin showed similar levels of accumulation in MCF7-WT and MCF7-BC19 cells, slightly lower levels in MCF7-AdrR cells, and no consistent response to Pgp modulators. These results support the continued investigation of sestamibi and tetrofosmin as agents for functional imaging of multidrug resistance in human cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Accumulation of sestamibi in lymphoma cell lines in vitro.

Although some authors have suggested that sestamibi imaging is useful in evaluation of patients with lymphoma, others have obtained equivocal results. This discrepancy has been further investigated in vitro using two patient-derived non-Hodgkin's lymphoma cell lines, OCI-Ly3 and OCI-Ly18. Sestamibi (0.2 MBq/ml) was added to a suspension of OCI-Ly3 or OCI-Ly18 cells and aliquots were removed over 1 h and centrifuged to determine cell-associated radioactivity. Further experiments studied the effect of addition of a P-glycoprotein (Pgp) modulator or alteration in plasma and/or mitochondrial membrane potentials. Accumulation of sestamibi reached plateau values within 30 min, but these values were 6-fold higher in OCI-Ly3 than in OCI-Ly18. Inhibition of Pgp function with GG918 or PSC833 did not affect OCI-Ly3 cells but increased accumulation in OCI-Ly18 cells 3-fold, indicating a moderate level of Pgp. However, both cell lines responded similarly to membrane potential alterations: hyperpolarization of the mitochondrial membrane with nigericin had little effect on accumulation: in contrast, depolarization of the plasma membrane with an isotonic high potassium buffer reduced accumulation of sestamibi to 52% of control and additional depolarization of the mitochondrial membrane with valinomycin further reduced accumulation to 12% of control levels. These studies suggest that there can be wide differences in accumulation between cell lines, in part due to Pgp-mediated efflux, but that both of these cell lines have highly polarized mitochondria with little further capacity for hyperpolarization.

Biological Transport↗
PubMed2000

BRU59-21, a second-generation 99mTc-labeled 2-nitroimidazole for imaging hypoxia in tumors.

UNLABELLED: Hypoxia in tumors is believed to be an important cause of local failure of radiotherapy in certain types of cancer. BRU59-21 (BMS194796) is a second-generation 99mTc-labeled 2-nitroimidazole that has been shown to offer improved characteristics for imaging myocardial ischemia. It has now been evaluated in models of tumor hypoxia. METHODS: Accumulation of BRU59-21 was compared with that of BMS181321 in Chinese hamster ovary cells incubated under aerobic or hypoxic conditions. The effects of competition with unlabeled nitroimidazoles and oxygen were studied. Biodistribution studies were performed in mice bearing transplanted KHT-C tumors in the leg. RESULTS: Within 5 min, BRU59-21 partitioned into aerobic cells in vitro at a level 10 times higher than external medium with no further increase over time. In hypoxic cells this initial partitioning was followed by selective accumulation to levels 5 times higher than in aerobic cells by 4 h. Low levels of oxygen (approximately 40 ppm) inhibited the maximal accumulation rate by 50%. Unlabeled misonidazole, a 2-nitroimidazole, inhibited accumulation of radioactivity, whereas tinidazole, a 5-nitroimidazole, enhanced accumulation; similar effects had been reported with BMS181321. Biodistribution studies in mice showed rapid clearance of radioactivity from the blood, resulting in enhanced tumor-to-blood ratios compared with BMS181321. Increasing the hypoxic fraction in the tumor by injection of nitro-L-arginine resulted in increased retention of tracer in the tumor without affecting other tissues. CONCLUSION: These results suggest that BRU59-21 warrants further investigation as an agent for imaging tumor hypoxia in the clinic.

Animals↗
PubMed1999

Influence of cell concentration in limiting the therapeutic benefit of P-glycoprotein reversal agents.

Pharmacological reversal of multidrug resistance (MDR) has been demonstrated frequently in tissue culture, but there has been minimal evidence of therapeutic effectiveness for solid tumours of animals, or in clinical trials. The concentration of cells in solid tumours is approx. 10(9) cells/ml but typically 10(5)-10(6) cells/ml in tissue culture. We investigated, therefore, the influence of cell concentration in culture on the ability of verapamil and cyclosporin A to increase the sensitivity of MDR-expressing cells to doxorubicin. Our data indicate that: 1. the uptake of the MDR substrates, doxorubicin and 99mTc-SestaMIBI, and the toxicity of doxorubicin decrease at higher cell concentration; 2. the effect of reversal agents on uptake and cytotoxicity of MDR substrates decreases markedly at higher cell concentration; 3. cell concentration effects are not overcome by continuous replenishment of drug to maintain a stable extracellular concentration. Our results suggest one mechanism which may contribute to the failure to observe reversal of MDR in animals, or in patients bearing established solid tumours.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

SPECT imaging of pre- and postsynaptic dopaminergic alterations in L-dopa-untreated PD.

BACKGROUND: In PD, presynaptic dopamine transporters are known to be decreased, whereas postsynaptic striatal D2 receptors are proposed to be upregulated. However, the relationship between these alterations is not clear. OBJECTIVE: To evaluate the ability of SPECT to detect both the pre- and postsynaptic dopaminergic alterations of the striatum in patients with L-dopa-untreated PD. METHODS: We studied 10 L-dopa-untreated patients with clinically mild PD and 21 age-matched normal controls. Individuals had both presynaptic [123I]beta-CIT dopamine transporter and postsynaptic [123I]IBF D2 SPECT studies 1 week apart. RESULTS: In PD patients, the dopamine transporter binding potential Rv ipsilateral/contralateral to the most affected limbs was 30%/41%, 41%/50%, and 59%/68% lower than controls for caudate, anterior putamen, and posterior putamen, respectively. These bilateral Rv decreases showed a lateralized difference more reduced in the contralateral striatum as well as intrastriatal differences most reduced in the posterior putamen. In contrast, in PD patients the D2 binding potential Rv ipsilateral/contralateral was 15%/16% higher for caudate, 18%/14% higher for anterior putamen, and 28%/31% higher for posterior putamen. These bilateral Rv increases showed no lateralized differences and less marked intrastriatal differences. The motor Unified Parkinson's Disease Rating Scale scores negatively correlated with dopamine transporter Rv but not with D2 Rv. CONCLUSIONS: SPECT imaging can detect characteristic dopaminergic alterations in the striatum of dopa-untreated PD patients including the upregulation of postsynaptic D2 receptors (denervation supersensitivity). SPECT is widely available and is a promising clinical tool to evaluate PD patients.

Aged↗
PubMed1999

Sentinel node detection and definition may depend on the imaging agent and timing.

PURPOSE: Two cases of sentinel lymph node imaging are presented in which the results are exceptions to what the literature generally defines as sentinel lymph nodes. In one case, Tc-99m antimony trisulfide colloid produced significantly different results than did Tc-99m tin colloid. In the second case, the results bring into question the definition of a sentinel node as the first in a lymphatic drainage pathway. MATERIALS AND METHODS: In one patient, lymphoscintigraphy was performed initially using Tc-99m antimony trisulfide colloid injected intradermally around a melanoma excision site. Repeated lymphoscintigraphy 1 month later, 1 hour before sentinel node excision, was done using Tc-99m tin colloid, a larger particle than antimony trisulfide colloid. The second patient, with a melanoma biopsied only, had sentinel node imaging performed using Tc-99m sulfide colloid, a particulate also larger than antimony trisulfide colloid and also 1 hour before sentinel node excision. RESULTS: In the first patient, imaging with the smaller antimony trisulfide colloid showed more lymphatic pathways and more sentinel nodes than with tin colloid. In the second patient, the first focus of retention of the imaging agent in the lymphatic pathway seen showed less intense accumulation than the next focus in the pathway, contrary to published reports that the sentinel node shows more intense accumulation than do nodes further downstream in a lymphatic pathway. CONCLUSIONS: There are exceptions to published characteristics of sentinel node lymphoscintigraphy, so care must be exercised in localizing sentinel nodes.

Antimony↗
PubMed1999

99Tcm-sestamibi imaging of inhibition of the multidrug resistance transporter in a mouse xenograft model of human breast cancer.

Sestamibi is known to be a substrate for P-glycoprotein, the membrane transporter which confers multidrug resistance by pumping certain chemotherapeutic agents out of tumour cells. In this study, the utility of sestamibi imaging for detecting inhibition of P-glycoprotein (Pgp) function by two potent, second-generation chemosensitizers, PSC833 and GG918, was assessed in a mouse xenograft model of multidrug-resistant human breast cancer, MCF7-AdrR. Preliminary in vitro studies confirmed that MCF7-AdrR cells accumulate only low levels of sestamibi and that both sensitizers inhibit transporter function to a similar extent, resulting in 20-fold higher accumulation of sestamibi. MCF7-AdrR cells were grown as a xenograft in SCID mice and sestamibi kinetics in the tumour were analysed by dynamic imaging (30 frames at a rate of one frame per minute). Administration of either chemosensitizer produced a dose-dependent slowing of the efflux rate of sestamibi compared to untreated tumours. The same effect was evident in two additional parameters: percent activity remaining at 30 min determined by imaging and sestamibi levels measured in excised tissues. These results show that sestamibi imaging can detect inhibition of Pgp function and suggest that this approach could be used clinically to document effective delivery of chemosensitizers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Functional morphometry of the striatum in Parkinson's disease on three-dimensional surface display of 123I-beta-CIT SPECT data.

UNLABELLED: The purpose of this study was to evaluate whether striatal morphology on a three-dimensional surface display of 123I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (123I-beta-CIT) SPECT data can be used as a diagnostic index for Parkinson's disease. METHODS: We studied 11 patients with mild Parkinson's disease and 21 age-matched controls. Triple-head SPECT scans were acquired for 30 min at 20 h after injection of 123I-beta-CIT. We measured the vertical height of the caudate head (H) and the length of the long axis of the striatum (L) on the three-dimensional surface display generated from SPECT data. The morphometric index of the striatum was defined as L/H. The power of L/H to discriminate Parkinson's disease and control groups was evaluated by discriminant function analysis and was compared with that of region of interest (ROI)-based 123I-beta-CIT binding measurements (V"3) and their ratios. RESULTS: The mean L/H ratios (ipsilateral/contralateral) to the most affected limbs were (33%/45%) lower in the Parkinson's disease group compared with the control group, respectively. All other ROI-based measures confirmed that dopamine transporter reductions were most severe in the contralateral posterior putamen (a 68% reduction in V"3). In 1 patient with a subsequent clinical diagnosis of drug-induced parkinsonism, all SPECT measures were normal. The contralateral putamen contributed most to the discriminatory power, and the contralateral L/H showed the best discriminatory power of all SPECT measures. CONCLUSION: These results suggest that striatal morphology on a three-dimensional display of 123I-beta-CIT SPECT data provides information of diagnostic significance for Parkinson's disease. This morphometry can be done without requiring technically demanding ROI analysis, and thus this technique may be suitable for routine clinical use.

Carrier Proteins↗
PubMed1999

External radioactive reference markers in SPECT imaging of the dopamine system.

OBJECTIVE: External radioactive reference markers have been used to localize the canthomeatal (CM) line and correct for head rotation in perfusion brain SPECT. This ensures that regardless of the subject's head position or rotation under the SPECT camera, reconstructed transaxial slices are reoriented parallel to the CM line. This study was undertaken to demonstrate the value of external radioactive reference markers in dopamine SPECT imaging. METHODS: We compared visual and marker methods of reorienting the transaxial slices between dopamine and perfusion brain SPECT studies, respectively. These consisted of imaging normal controls and patients with Alzheimer's or Parkinson's disease using a triple-head camera. Intra- and interoperator variability of the visual and marker methods of reorientation was determined for both perfusion and dopamine studies. RESULTS: In both intra- and interoperator studies, the variability of image reorientation was significantly reduced (P = 0.0066 and 0.014, respectively) by using the marker method on dopamine images. The variability of reorientation using the marker method for a single operator with dopamine images was 3.0% coefficient of variation (CV), and for the interoperator study (5 different operators) this was 7.0% CV. CONCLUSION: This study demonstrated that SPECT imaging of the dopamine system with external radioactive reference markers significantly reduced the variability of determining the angle of reorientation. This resulted in a standardized and consistent method of reorienting transaxial slices, allowing comparison within and between subjects of pre- and postsynaptic dopamine SPECT studies.

Alzheimer Disease↗
PubMed1998

Studies of 99mTc-BnAO (HL-91): a non-nitroaromatic compound for hypoxic cell detection.

PURPOSE: Solid tumours of similar type and stage can vary widely in their hypoxic cell fraction. Such cells may be prognostic for aggressive, metastatic, and radiation-resistant disease. A 99mtechnetium (99mTc)-labelled non-nitroaromatic agent, butyleneamine oxime (99mTc-BnAO) or HL-91 (Amersham International, Inc., Amersham, UK) has been evaluated both in vitro and in vivo for its possible efficacy as a noninvasive marker for the clinical detection of hypoxic cells in solid tumours. MATERIALS AND METHODS: Suspension cultures of Chinese hamster ovary (CHO) cells under controlled levels of oxygen were used to measure the oxygen dependency of 99mTc-BnAO accumulation. V79 cells grown as multilayers on a semipermeable membrane served as an in vitro model for drug penetration through the extravascular space of the tumour. C3H mice bearing KHT-C leg tumours were the in vivo models for selective drug accumulation as a function of time after i.v. administration of 99mTc-BnAO. RESULTS: 99mTc accumulated selectively in hypoxic vs. aerobic cells, resulting in a 9 +/- 2-fold differential in radioactivity per cell at 4 h. The k(m) for this selective accumulation was 20 ppm of oxygen. The labelled drug was equally effective in penetrating the cellular multilayer under aerobic or hypoxic conditions. In vivo measurements indicated favourable labelling of solid tumours containing hypoxic cells with 1% of the total activity per g of tumour, a tumour-to-blood ratio of 1.2, and a tumour-to-muscle ratio of 4.6 at 4 to 6 h after drug administration. In contrast to more lipophilic 99mTc- labelled compounds, excretion was primarily via the urinary tract. Nitro-L-arginine selectively increased solid tumour labelling over normal tissue. CONCLUSIONS: 99mTc-BnAO or HL-91 is a promising agent for clinical studies of tumour hypoxia, although the mechanism of its selective hypoxic cell accumulation remains unexplained.

Animals↗
PubMed1998

Prostate-specific antigen induction by a steroid hormone in T47D cells growing in SCID mice.

Previous studies revealed that prostate-specific antigen (PSA) is present in > 30% of human breast tumor cytosols. Survival analysis showed that patients with PSA-producing tumors have a reduced risk for relapse, suggesting PSA to be an independent favorable prognostic marker for a large subset of breast cancer patients. The present investigation established an in vivo model for the induction of PSA in human breast cancer tumors growing as xenografts in severe combined immunodeficient (SCID) mice. The human mammary cancer cell-line T47D was grown i.m. in female mice. When the tumor and leg diameter reached 10 mm, the mice were stimulated daily with norgestrel for either 5 or 7 days to produce PSA, and sacrificed on day 8. The prostate cancer cell-line LNCaP was grown in male mice and functioned as a positive control for PSA production. After T47D and LNCaP mice were sacrificed, a highly sensitive immunofluorometric assay was used to analyze the PSA concentration in the tumor, muscle, liver, and kidney cytosols. Norgestrel-stimulated T47D mice showed significantly more PSA in the tumors compared to tumors of the control mice. However, PSA levels in tumors of the stimulated mice were significantly lower than those in the LNCaP xenografts. No PSA levels above background were present in the blood and normal tissue of the norgestrel-stimulated or control T47D xenografts. This mouse model will be a valuable tool for investigating and screening new therapies for a subgroup of breast cancer patients who have significant PSA concentrations in their tumors.

Animals↗
PubMed1998

Age-related changes in D2 receptor binding with iodine-123-iodobenzofuran SPECT.

UNLABELLED: The purpose of this study was to evaluate the effects of age on D2 receptor binding with 123I-iodobenzofuran (IBF) SPECT. METHODS: Subjects were 40 healthy volunteers (age 19-83 yr), including 6 who had test/retest studies. Scans were acquired with a triple-head SPECT camera 3 hr postinjection of IBF (300 MBq). Striatal regions (caudate and putamen) were defined by two different region-of-interest (ROI) sets consisting of large volumes [(CLVs), 2.2 and 6.6 m] and small volumes [(SVs), 0.6 and 1.3 ml]. D2 binding (Rv=V3/V2) was quantified using our previously proposed multilinear regression technique. Effects of age on D2 binding were evaluated by fitting linear, exponential and logarithmic models. RESULTS: The mean Rvs were 26% lower than LV for both putamen and caudate than the corresponding values from the SV due to the partial-volume effect. Although the identifiability of Rv using SV deteriorated slightly, the test/retest reproducibility of Rv measurements was equally excellent for LV and SV. The mean Rvs were 11% higher for putamen compared with those for caudate. D2 binding declined significantly with age (p < 10(-5)) for all three models. The nonlinear models were slightly superior to the linear model in describing the relationship between Rv and age. In these models, D2 binding declined with age, equally for caudate and putamen at 7%-13% per decade; the decline was progressively smaller with age. CONCLUSION: IBF SPECT permitted reliable measurements of D2 binding in the caudate or putamen separately using small ROI volumes that significantly improved the quantitation loss from the partial-volume effect. Our results agreed with previous PET and postmortem findings of D2 binding losses with age. However, these age effects may be nonlinear. Age-related changes in D2 binding must be taken into consideration in clinical IBF SPECT investigations.

Adult↗
PubMed1997

Modifying the in vitro accumulation of BMS181321, a technetium-99m-nitroimidazole, with unlabelled nitroaromatics.

BMS181321, [99mTc]oxo[[3,3,9,9-tetramethyl-1-(2-nitro-1H-imidazol-1-yl)-4,8-diaz aundecane-2,10-dione dioximato]-(3)-N,N',N",N"']technetium, is a 99mTc-nitroimidazole that is being investigated as a hypoxic marker in tumors. Due to the high specific activity of 99mTc, the concentration of BMS181321 used in its applications is very low. Metabolic depletion and non-specific binding of the drug may limit its ability to fully map out hypoxic regions. An attempt has been made to modify the in vitro accumulation of BMS181321 in hypoxic Chinese hamster ovary (CHO) cells with unlabelled nitroaromatics. The 2-nitroimidazole etanidazole (0.08 to 8 mM) caused a concentration-dependent decrease in BMS181321 accumulation to 70-28% and metabolism to 70-40% of the control level in hypoxic cells at 4 hr. In contrast, the 5-nitroimidazole tinidazole (0.09 to 9 mM) caused a concentration-dependent increase in BMS181321 accumulation to 110-170% and metabolism to 100-150% of the control level in hypoxic cells at 4 hr. Nitroaromatics with an electron affinity similar to or greater than that of BMS181321 inhibited its accumulation and metabolism, and 5-nitroimidazoles, which have an electron affinity lower than that of BMS181321, enhanced its accumulation and metabolism. The enhanced accumulation with the addition of metronidazole was not observed in the presence of low oxygen levels or of a nitrofuran of higher electron affinity than BMS181321. These results suggest that a competition for reducing equivalents and/or for the BMS181321 radical anion itself can occur in cells, leading to the inhibition of BMS181321 reduction in the presence of nitroaromatics of similar or greater electron affinity. A transfer of electrons from the radical anion form of the reduced 5-nitroimidazole to the more electron affinic BMS181321 compound may occur, causing increased hypoxic accumulation of BMS181321.

Animals↗
PubMed1997

Accumulation of 99mTc-HMPAO and 99mTc-ECD in rodent and human breast tumor cell lines in vitro.

The accumulation of 99mTc-HMPAO and 99mTc-ECD was studied in rat (MatB) and human (MCF-7) breast tumor cell lines in vitro as a function of incubation time. The general pattern was the same for both tracers and both cell lines: the tracer rapidly and extensively accumulated in the cells but a plateau was reached in 15-30 minutes. Accumulation of HMPAO was higher than that of ECD, did not show a difference between rat and human cells, and correction of HMPAO data for intracellular sequestration and extracellular metabolism resulted in a linear increase in accumulation with time. In contrast, accumulation of ECD was approximately 2-fold higher in human cells than in rat cells but after correction for sequestration and metabolism a plateau remained. These experiments show differences between HMPAO and ECD in their accumulation and retention in breast cancer cells in vitro and support that the need for further work on the potential clinical role for HMPAO in tumor characterization.

Animals↗
PubMed1997

In vivo animal tests of an artifact-free contrast agent for gastrointestinal MRI.

A variety of shortcomings are associated with most currently used gastrointestinal contrast agents for magnetic resonance imaging (MRI). Artifacts resulting from peristalsis and other motions in the abdominal region are produced by many positive contrast agents (which increase signal intensity). Although this is not a problem for negative contrast agents (which decrease signal intensity), some negative contrast agents produce magnetic susceptibility artifacts that are especially pronounced at high field strength and with gradient echo pulse sequences. These susceptibility artifacts are produced by both paramagnetic and diamagnetic agents. It has been demonstrated in phantoms, however, that susceptibility matching can be used to produce contrast agents with desirable relaxation and contrast properties but without deleterious susceptibility artifacts. We now report results of animal tests of such an oral contrast agent, consisting of a suspension of superparamagnetic iron oxide particles and diamagnetic barium sulfate particles, compared to individual suspensions of the iron oxide and of the barium sulfate. Iron oxide was the least effective and the matched susceptibility mixture was the most effective for the intestine, which has traditionally been the most difficult region of the GI tract to visualize clearly. Matched susceptibility mixtures, which are inherently able to yield images free of susceptibility artifacts without compromising contrast, show promise of being improved oral negative contrast agents for use in gastrointestinal MRI.

Administration, Oral↗
PubMed1997

Simplified quantification and reproducibility studies of dopamine D2-receptor binding with iodine-123-IBF SPECT in healthy subjects.

UNLABELLED: The purpose of this study was to assess the feasibility of a simplified SPECT scan protocol to quantify D2-receptor binding using [123I]iodobenzofuran (IBF) and to evaluate reproducibility of quantitative IBF-SPECT imaging without blood data. METHODS: Twenty healthy volunteers participated in the study, six had test/retest studies separated by 1 wk. Scans were acquired every 5 min for 180 min using a triple-headed SPECT camera after a bolus injection of IBF (292 MBq). The receptor parameter was determined by using our previously proposed variation of graphical analysis that derives the distribution volume ratio (Rv = V3/V2) from multiple scan data without blood data. Rv' was determined from three 20-min scan data obtained at 0-20, 50-70 and 160-180 min postinjection and compared with Rv as determined from scans obtained at 0-180 min. RESULTS: The mean Rv' (2.93 +/- 0.59) underestimated the mean Rv (3.10 +/- 0.50) by 5%. The mean variability (mean percent absolute difference) between Rv' and Rv was low (10%) with excellent reliability (intraclass correlation coefficient, p = 0.90). The relationship between Rv' and Rv was linear (r = 0.95, p < 10(-5)). The mean test/retest Rv and mean test/retest Rv' were (3.19 +/- 0.70/3.18 +/- 0.80) and (3.16 +/- 0.81/3.01 +/- 0.94), respectively, and these measures were not significantly different between test/retest studies. The mean test/retest variability of Rv was low (5%) with excellent reliability (p = 0.98). In addition, the mean test/retest variability of Rv' was low (10%) with excellent reliability (p = 0.94). CONCLUSION: Three short (20 min) IBF-SPECT scans allowing for rest periods between scans permit reliable measurements of the dopamine D2-receptor parameter V3/V2. Quantitative IBF-SPECT imaging without blood data is reliable and reproducible.

Adult↗
PubMed1997

Regional differences in technetium-99m-ECD clearance on brain SPECT in healthy subjects.

UNLABELLED: The aim of this study was to evaluate the in vivo stability of ECD brain SPECT. METHODS: Twenty normal volunteers (35.4 +/- 9.1 yr) each had six ECD scans at 30, 60, 120, 240, 360 and 480 min postinjection. Each scan was acquired for 24 min using a triple-head SPECT system. Average counts per pixel were measured from frontal, temporal, parietal, occipital, cerebellum, basal ganglia, thalamus and white matter regions. ECD clearance rates were calculated by fitting regional time activity data to a monoexponential equation. Regional gray-to-white matter (G/W) and gray-to-cerebellum (G/C) ratios were calculated for each scan. Analysis of variance was used to compare regional ECD clearance and ratio measurements. RESULTS: The average ECD clearance was 4.3%/hr. There was a significant regional variation in the ECD clearance, being higher for occipital (6.34%/hr) but lower for both white matter (2.39%/hr) and thalamus (2.45%/hr). Both G/W and G/C ratios showed a significant regional variation with time. The overall G/W ratio was 2.13 at 30 min and became progressively lower after 2 hr, reaching 1.78 at 8 hr. All regional G/W ratios declined with time except for thalamus where it remained constant at 2.15. The overall G/C ratio was 0.984 at 30 min but it declined after 4 hr, reaching 0.955 at 8 hr. All regional G/C ratios declined with time except for thalamus where it increased progressively from 0.955 to 1.120 at 8 hr. CONCLUSION: ECD clears from normal brain slowly and shows a significant regional variation. As a result, G/W contrast begins to decrease after 2 hr and the gray-matter activity pattern becomes significantly different after 4 hr. Therefore, the optimal imaging time may be between 30-120 min. However, images obtained up to 4 hr still maintain the initial gray-matter activity pattern.

Adult↗