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Biomedical subjects

R D Neirinckx

Publications and source records attributed to R D Neirinckx.

At least 19 recordsLinked to original sources
PubMed1988

The retention mechanism of technetium-99m-HM-PAO: intracellular reaction with glutathione.

Preparations of d,l- and meso-hexamethylpropyleneamine oxime (HM-PAO) labeled with technetium-99m were added to rat brain homogenates diluted with phosphate buffer (1:10). The conversion of d,l-HM-PAO to hydrophilic forms took place with an initial rate constant of 0.12 min-1. Incubation of the brain homogenate with 2% diethyl maleate for 5 h decreased the homogenate's measured glutathione (GSH) concentration from 160 to 16 microM and decreased the conversion rate to 0.012 min-1. Buffered aqueous solutions of glutathione rapidly converted the HM-PAO tracers to hydrophilic forms having the same chromatographic characteristics as found in the brain homogenates. The rate constant for the conversion reaction of d,l-HM-PAO in GSH aqueous solution was 208 and 317 L/mol/min in two different assay systems and for meso-HM-PAO the values were 14.7 and 23.2 L/mol/min, respectively. Rat brain has a GSH concentration of about 2.3 mM and the conversion of the d,l-HM-PAO due to GSH alone should proceed with a rate constant of 0.48 to 0.73 min-1 and be correspondingly 14-fold slower for meso-HM-PAO. In human brain, the in vivo data of Lassen et al. show a conversion rate constant of 0.80 min-1. This correspondence of values supports the notion that GSH may be important for the in vivo conversion of 99mTc-labeled HM-PAO to hydrophilic forms and may be the mechanism of trapping in brain and other cells. A kinetic model for the trapping of d,l- and meso-HM-PAO in tissue is developed that is based on data of GSH concentration in various organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Assessment of the arterial input curve for [99mTc]-d,l-HM-PAO by rapid octanol extraction.

The in vitro conversion of the lipophilic molecule [99mTc]-d,l-hexamethylpropyleneamine oxime [( 99mTc]-d,l-HM-PAO) to a hydrophilic form was studied in saline, plasma, and blood at 37 degrees C by paper chromatography and by octanol extraction. The octanol:saline ratio was 79.9. From this value and the corresponding octanol: plasma and octanol:blood partitioning values, an estimate of the transport of the lipophilic compound by various components of blood was made: 20% is carried in hemoglobin, 53% by the plasma proteins and 27% by the water phases of the red blood cell and plasma. Octanol extraction provided a rapid method for measuring the radiochemical purity (RCP) of lipophilic [99mTc]-d,l-HM-PAO. In saline, the RCP declined with a half-life of more than 1 h. In human plasma and whole blood, the conversion of [99mTc]-d,l-HM-PAO was biexponential due to the differences in the conversion rates of the d and l isomeric forms. The initial half-life representing the conversion rate of the l form was 1.7 min in blood and 1.4 min in plasma, while the conversion half-life of the d form was 7.4 and 24.4 min, respectively. In vivo, the RCP of arterial blood sampled after an i.v. bolus injection showed an initial peak value of 75% (68-79%) during the initial, first passage of the bolus. It declined to approximately 35% (29-40%) after 1.5 min and reached very low levels (about 1%) at 6 to 10 min. Quantitative measurements of cerebral blood flow using [99mTc]-d,l-HM-PAO necessitates a rapid method for RCP determination in arterial blood such as the one described here.

Arteries↗
PubMed1988

Extraction of [99mTc]-d,l-HM-PAO across the blood-brain barrier.

The initial extraction (E) across the blood-brain barrier (BBB) of [99mTc]-d,l-HM-PAO after intracarotid injection was measured in 14 Wistar rats and 6 patients using the double indicator, single injection method with Na-24 as the cotracer. In both series, cerebral blood flow (CBF) was measured using the initial slope of the xenon-133 washout curve after intracarotid bolus injection. In rats, bolus size (20 or 120 microliters), bolus type (saline or 10% albumin), or CBF were changed. First-pass extraction was dependent on CBF (p less than 0.001): With a small bolus of saline and at resting CBF (0.75 ml/g/min), E was 0.81, decreasing to 0.56 at a high CBF (1.5 ml/g/min). The calculated permeability surface area product (PS) increased linearly from 1.2 to 1.5 ml/g/min when CBF increased from 0.8 to 1.5 ml/g/min (p less than 0.01). E was found to increase when the bolus volume of saline was increased from 20 to 120 microliters, while using a 120 microliters bolus containing 10% albumin resulted in a decrease in E. This suggests that HM-PAO binding to albumin is not totally and rapidly reversible during a single passage through brain capillaries and that binding to blood elements may reduce the apparent extraction across brain capillaries. In patients using a bolus of 1 ml saline, E decreased linearly with increasing CBF (r = -0.81, p less than 0.001). For a CBF of 0.59 ml/g/min and an average apparent E of 0.72, an apparent PS product of 0.76 ml/g/min was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Osteomyelitis.

The use of 111In-labelled granulocyte scintigraphy is recognized as a reliable method for detecting osteomyelitis and has similar sensitivity and significantly increased specificity compared to bone scintigraphy and 67Ga studies. Recent published work using pure granulocytes labelled with 111In tropolonate to detect osteomyelitis resulted in sensitivity of 100% and specificity of 92%. 99Tcm as an alternative granulocyte label offers advantages of convenience, lower radiation dose and higher image resolution. We have scanned 20 patients with suspected osteomyelitis using autologous granulocytes labelled with 99Tcm hexamethylpropyleneamineoxime (HMPAO), 12 of whom had prosthetic joints. The scan results were correlated with clinical, radiographic, microbiological and histological findings. Sensitivity was 100% and specificity was 93% which compares favourably with results obtained using 111In-labelled granulocytes. We believe that labelled granulocyte scintigraphy is a useful investigation in the diagnosis of osteomyelitis and that 99Tcm HMPAO appears to be at least as useful as 111In as the labelling agent.

Granulocytes↗
PubMed1988

Inflammation: imaging with Tc-99m HMPAO-labeled leukocytes.

Leukocytes labeled with technetium-99m hexamethylpropyleneamine oxime (HMPAO) were used in 100 patients: 32 with suspected inflammatory bowel disease, 17 with fever of unknown origin, 21 with suspected abdominal sepsis, 20 with suspected bone sepsis, seven with bronchiectasis, and three with recent myocardial infarction. The distribution of activity in patients subsequently shown not to have inflammatory bowel disease was similar to that previously described for indium-111-labeled leukocytes. However, in this study, activity was also seen in the kidneys and bladder and occasionally the gallbladder on both early (1-3 hours) and late (24 hours) views, and in the colon in late views. Migration of Tc-99m-labeled granulocytes was seen in inflammatory disease as early as 30 minutes after injection, while normal bowel activity was not seen before 4 hours. The sensitivity of Tc99m-labeled leukocytes in the detection of inflammation was 100%, the specificity was 95%.

Colitis↗
PubMed1987

Technetium-99m d,l-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion.

Following investigation of a large number of new ligands based upon propylene amine oxime (PnAO) the d,l-diastereoisomer of hexamethyl propyleneamine oxime (HM-PAO) was selected as the preferred ligand for 99mTc as a tracer for cerebral perfusion imaging. The neutral, lipophilic 99mTc complex of d,l-HM-PAO was formed in high yield by stannous reduction of 99Mo/99mTc generator eluate using a kit formulation of the ligand. Two minutes following i.v. administration of this complex in rats, 2.25% of the injected dose appears in the brain. Little washout of the tracer is observed up to 24 hr postinjection. By qualitative autoradiographic comparison with iodoantipyrine this new radiopharmaceutical displays blood flow dependent brain uptake with little redistribution of the tracer over time. The lipophilic 99mTc complex converts slowly in vitro to a secondary complex. This conversion process may account for the ability of [99mTc]d,l-HM-PAO to be retained within the brain without redistribution.

Animals↗
PubMed1987

Initial experience with technetium-99m HM-PAO brain SPECT.

Technetium-99m hexamethylpropyleneamineoxime ([99mTc]HM-PAO) brain single photon emission computed tomography (SPECT) was performed with a dual head rotating scintillation camera. Normal tracer distribution and side/side differences of counting rates were obtained in 11 healthy volunteers. Almost stable gray/white matter ratios were found (1.97-2.1) in one normal subject during 2 hr after tracer administration. Eighty-three investigated patients had the following diagnoses (in parentheses is percent of positive findings in each group): cerebral vascular disease 18 (94.4%), epilepsy 23 (82.6%), extrapyramidal disorders 8 (100%), dementia 12 (100%), headache 11 (63.6%), psychiatric disorders 11 (27.3%). In addition, SPECT was performed in 28 male volunteers during motor or visual imagery tasks and a significant increase (p = 0.035) of relative tracer deposition was observed in the left inferior occipital region during visual imagery when compared with motor imagery. The results indicate that [99mTc]HM-PAO SPECT is valuable for demonstrating pathologic and physiologic changes of the brain.

Adult↗
PubMed1987

Serial studies of cerebral blood flow using 99Tcm-HMPAO: a comparison with 133Xe.

We have compared the regional distribution of 99Tcm-HMPAO with regional cerebral blood flow (rCBF). CBF was measured by single photon emission computerized tomography (SPECT) using a TOMOMATIC 64 after 133Xe inhalation in 41 patients. With the same SPECT device the distribution of 99Tcm-HMPAO was measured after i.v. injection. High resolution (HR) and low resolution (LR) studies were performed yielding a resolution of 6 to 10 mm (HR) and 15 to 20 (LR). 99Tcm-HMPAO images showed close resemblance to xenon-133 CBF tomograms. Only about 20% of the (decay corrected) brain counts were lost during the first 24 h post injection. A slight decrease in contrast was measured comparing side-to-side asymmetry ratios from the serial studies. This loss of contrast is mainly due to back-diffusion and clearance of a part of the 99Tcm-HMPAO complex from the brain. It could be corrected for by a linearization algorithm. The slight loss of contrast will not be of any importance for the clinical use of this tracer complex.

Brain↗
PubMed1986

Clinical experience with 99mTc-hexamethylpropylene-amineoxime for labelling leucocytes and imaging inflammation.

Hexamethylpropylene-amineoxime (HMPAO) forms a lipid-soluble neutral complex with 99mTc which is rapidly incorporated into leucocytes in vitro. In six patients with suspected or known inflammatory disease, a "mixed" leucocyte suspension isolated from 85 ml blood anticoagulated with acid-citrate-dextrose was labelled by 99mTc-HMPAO with a mean efficiency of 47% (SE2%), of which 78% (3) was taken up by granulocytes. Activity eluted more rapidly from other cell types in vitro than from granulocytes, which remained firmly labelled. Mean initial biodistribution of the label and granulocyte recovery in blood of 32% (8) at 30-40 min showed that the granulocytes were not significantly activated during labelling. All six patients were positive for inflammatory disease, as early as 30 min in five patients and at 3 h in the sixth; they all remained positive at 20-24 h. Four patients also received 111In-labelled "pure" granulocytes. In terms of detail, the 99mTc images were comparable or superior to the 111In images.

Adult↗
PubMed1986

Evaluation of a 99Tcm bound brain scanning agent for single photon emission computed tomography.

D,L HM-PAO-99Tcm (PAO) is a lipophilic tracer complex which is avidly taken up by the brain. We have compared the regional distribution of PAO with regional cerebral blood flow (CBF). CBF was measured by single photon emission computed tomography (SPECT) by Tomomatic 64 after 133Xe inhalation in 41 patients. With the same SPECT the distribution of PAO was measured after intravenous injection. High resolution (HR) and low resolution (LR) studies were performed yielding a resolution of 6-10 mm (HR) and 15-20 mm (LR). PAO images showed close resemblance to 133Xe CBF tomograms. Only 20 per cent of the (decay corrected) brain counts were lost during 24 hours.

Brain↗
PubMed1986

A comparative study of the brain uptake and early kinetics of 99mTc-dl HM-PAO and other PnAO derivatives in baboons.

Derivatives of propylene-amine-oxime (PnAO) have been synthesized which form a neutral lipid-soluble complex with 96mTc and can be supplied as freeze-dried kits. The complexes cross the intact blood-brain barrier. This report shows the brain uptake, early kinetics and biodistribution in normal adult baboons of 5 99mTc-PnAO derivatives and 2 isomers of one of the tested derivatives (HM-PAO). The brain uptake of the favoured dl-isomer of HM-PAO reaches its maximum of 4.3% (whole brain/whole body) 1 min p.i. and a clearance of less than 8% was observed 23 min p.i.

Animals↗
PubMed1986

Technetium-99m-d, 1-HM-PAO: a new radiopharmaceutical for imaging regional brain perfusion using SPECT--a comparison with iodine-123 HIPDM.

A new radiopharmaceutical, technetium-99m hexamethylpropyleneamine oxime (99mTc-d, 1-HM-PAO), has been reported to cross the blood-brain-barrier and to distribute in brain in proportion to regional blood flow. This study reports brain imaging obtained with 99mTc-d,1 HM-PAO in 20 subjects; seven without evidence of cerebral disease and 13 with cerebrovascular disorders. In 16 patients comparative data were available with N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine ([123I]HIPDM). Technetium-99m-d, 1-HM-PAO is retained sufficiently long to allow single photon emission computed tomography (SPECT) with widely available rotating gamma camera systems. The kinetics demonstrated a rapid brain uptake and prolonged retention of activity in cerebral structures. Good tomographic images are obtained with much higher uptake in gray than in white matter. Blood flow maps are comparable to those achieved with [123I]HIPDM and established strokes were clearly seen, with similar details as in HIPDM studies. Delayed studies showed that the distribution in the brain remained virtually unchanged. Technetium-99m-d, 1-HM-PAO imaging appears particularly promising in routine examination of patients with cerebrovascular disorders.

Brain↗
PubMed1986

Technetium-99m HM-PAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies.

A total of nine normal volunteer subjects were studied with three forms of [99mTc] hexamethylpropyleneamineoxime (HM-PAO), a potential cerebral blood flow imaging agent. One, the d,l isomer, showed 4.1% uptake in the brain which remained constant over 8 hr. There was good differentiation between uptake in gray and white matter on tomographic slices. We propose that this agent may allow regional cerebral blood flow imaging to be performed on a routine basis.

Adult↗
PubMed1985

A 99Tcm-labelled radiotracer for the investigation of cerebral vascular disease.

The first clinical data is given on 99Tcm-hexamethylpropyleneamine oxime (HM-PAO) in normal subjects and patients with established stroke. Regional cerebral blood flow maps (rCBF) have been recorded and displayed in tomographic mode with this new radiopharmaceutical. Good images were obtained, comparable to those achieved with 123I-isopropylamphetamine (IMP).

Amphetamines↗
PubMed1979

Cardiac imaging with tantalum-178.

Tantalum-178 is a potential tracer for the first transit studies of the heart. It has a short physical half-life (9.3 minutes) and is obtained as a generator product from its long-lived (21.3 days) parent, tungsten-178. First transit studies were performed in the monkey and dog following the intravenous injection of 20 mCi (740 MBq) of tantalum-178. Imaging was performed with a large field of view single crystal camera and a multicrystal camera. Pulmonary dilution curves were derived for the analysis of left-to-right intracardiac shunting and high temporal resolution studies were obtained to assess left ventricular function and to measure left ventricular ejection fraction. The short physical half-life of tantalum-178 permits fraction. The short physical half-life of tantalum-178 permits multiple sequential studies with reduced patient radiation dose compared to the current radionuclide of choice, technetium-99m.

Angiocardiography↗
PubMed1979

Potential column chromatography generators for ionic Ga-68. I. Inorganic substrates.

Chemical separations for Ga-68 from Ge-68 using adsorption chromatography on inorganic materials are described. The adsorbents used were TiO2, ZrO2, and SiO2. Distribution coefficients for Ge and Ga on these absorbents were determined as a function of reagent concentration and duration of equilibration. The distribution coefficient (w/w) for Ge on SiO2 reached 250 in 6 N HNO3, whereas Ga was no significantly adsorbed. Therefore, Ga-68 can be collected with a mall volume of 6 N HNO3 eluent. By contrast, large volumes of 1 N HNO3 were necessary to collect Ga-68 from ZrO2, since the KD of Ga under these circumstances was about 50. The Ga-68 eluted from TiO2 was chemically contaminated with titanates and would require additional chemical manipulation in order to make it injectable. All the adsorbents could lead to chromatographic systems that would allow acceptable chemical separations. However, the specific requirements for a radionuclide generator, usable in a hospital environment, make the SiO2-based system the most attractive.

Chromatography↗