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Biomedical subjects

K Y Gulenchyn

Publications and source records attributed to K Y Gulenchyn.

At least 19 recordsLinked to original sources

Treating the right patient at the right time: access to cardiovascular nuclear imaging.

Cardiovascular nuclear medicine uses agents labelled with radioisotopes that can be imaged with cameras (single-photon emission tomography [SPECT] or positron emission tomography [PET]) capable of detecting gamma photons to show physiological parameters such as myocardial perfusion, myocardial viability or ventricular function. There is a growing body of literature providing guidelines for the appropriate use of these techniques, but there are little data regarding the appropriate timeframe during which the procedures should be accessed. An expert working group composed of cardiologists and nuclear medicine specialists conducted an Internet search to identify current wait times and recommendations for wait times for a number of cardiac diagnostic tools and procedures, including cardiac catheterization and angioplasty, bypass grafting and vascular surgery. These data were used to estimate appropriate wait times for cardiovascular nuclear medicine procedures. The estimated times were compared with current wait times in each province. Wait time benchmarks were developed for the following: myocardial perfusion with either exercise or pharmacological stress and SPECT or PET imaging; myocardial viability assessment with either fluorodeoxyglucose SPECT or PET imaging, or thallium-201 SPECT imaging; and radionuclide angiography. Emergent, urgent and nonurgent indications were defined for each clinical examination. In each case, appropriate wait time benchmarks were defined as within 24 h for emergent indications, within three days for urgent indications and within 14 days for nonurgent indications. Substantial variability was noted from province to province with respect to access for these procedures. For myocardial perfusion imaging, mean emergent/urgent wait times varied from four to 24 days, and mean nonurgent wait times varied from 15 to 158 days. Only Ontario provided limited access to viability assessment, with fluorodeoxyglucose available in one centre. Mean emergent/urgent wait times for access to viability assessment with thallium-201 SPECT imaging varied from three to eight days, with the exception of Newfoundland, where an emergent/urgent assessment was not available; mean nonurgent wait times varied from seven to 85 days. Finally, for radionuclide angiography, mean emergent/urgent wait times varied from two to 20 days, and nonurgent wait times varied from eight to 36 days. Again, Newfoundland centres were unable to provide emergent/urgent access. The publication of these data and proposed wait times as national targets is a step toward the validation of these recommendations through consultation with clinicians caring for cardiac patients across Canada.

Canada↗

Cardiac risk stratification using dipyridamole myocardial perfusion imaging and ambulatory ECG monitoring prior to vascular surgery.

Both dipyridamole myocardial perfusion imaging (cardiolite) and ambulatory ECG monitoring (Holter) for silent ischaemia have been found to be useful for stratification of cardiac risk in patients undergoing vascular surgery. The purpose of this study was to compare the diagnostic accuracy of these two non-invasive tests for prediction of perioperative cardiac events. One hundred patients (86 males, 14 females; mean age 67 +/- 8 years) underwent out-patient 48 h Holter monitoring and cardiolite imaging prior to vascular surgery (70 abdominal aortic aneurysm, 21 aortobifemoral, nine femoralpopliteal grafts). Ischaemia on Holter was defined as one or more episodes of ST segment depression 1 mm or greater, lasting 1 min or longer. Myocardial perfusion imaging was carried out with the high dose dipyridamole protocol (0.84 mg/kg), cardiolite and planar imaging. Ischaemia was defined as a segmental perfusion abnormality following dipyridamole with improved perfusion on rest imaging. Holter was positive for ischaemia in 34/100 patients (34%). Cardiolite scans were positive for ischaemia in 30/100 patients (30%). Perioperative myocardial infarction occurred in nine patients (two cardiac deaths). [table: see text] The diagnostic accuracy of the two tests was similar, with a low positive predictive value of 15-20%, and an extremely high negative predictive value of 94-96%. The event rate in patients with both tests negative was 2/48 (4.2%), with only one test positive 3/40 (7.5%) and with both tests positive 4/12 (33%). A reasonable approach to risk stratification would be to obtain either a Holter or cardiolite scan initially.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vitro comparison of HMPAO and gentisic acid for labelling leukocytes with 99mTc.

Leukocytes can be labelled with 99mTc using HMPAO and gentisic acid methods. We compared the two methods with respect to labelling efficiency on mixed leukocytes and isolated polymorphonuclear (PMN) and mononuclear (MN) cells, and the in vitro stability of the label. HMPAO produced approximately 70% labelling efficiency on mixed or PMN cells and the label was stable in saline or plasma. Labelling efficiency on MN was only 14% and was less stable. Gentisic acid produced a labelling efficiency of 52% on PMN and 35% on MN; both were stable in saline but less stable in plasma. In conclusion, HMPAO produces higher labelling efficiency and the label shows greater in vitro stability in plasma. However, gentisic acid is much less expensive to use, allows labelling of MN cells, and should result in more favourable microdosimetry. Preliminary clinical results suggest that gentisic acid is equivalent to HMPAO but has the advantage of being much cheaper.

Costs and Cost Analysis↗

A kit for labelling erythrocytes or leukocytes with technetium-99m.

A pretinning method for labelling erythrocytes with technetium-99m (99mTc) in vitro has been developed using a kit which contains stannous chloride stabilized with gentisic acid. Labelling efficiency was 97.3% (SD 1.4%) for 80 patients. The method requires less time than the Brookhaven kit and results in a smaller volume for reinjection but provides equivalent clinical results. We have previously shown that leukocytes labelled with 99mTc using the same gentisic acid kit are clinically equivalent to those labelled with HMPAO; thus, the kit is versatile and cost-effective.

Erythrocytes↗

Cerebral perfusion imaging with technetium-99m HMPAO following cerebral trauma. Initial experience.

Thirteen patients with cerebral trauma were studied for cerebral perfusion by the use of Tc-99m HMPAO scanning. CT imaging was performed on nine patients. Because of their clinical condition, four patients were scanned only in the planar mode to help establish the diagnosis of brain death. Other indications for study included gunshot wound and blunt or sharp object trauma with or without skull fracture. In all cases, HMPAO scans showed defects with a quality equivalent to or greater than that demonstrated by CT. Our initial results suggest that HMPAO may predict the degree of permanent damage and which patients may develop post-traumatic headache. A diagnosis of brain death can be established without the withdrawal of medical therapy.

Brain↗

Radiopharmaceutical factors in the variable quality of [99mTc]HM-PAO images of the brain.

Variability in the quality of [99mTc]HM-PAO images of the brain has been attributed to differences between kits and the addition of excessive amounts of pertechnetate to the kits. A retrospective study showed no significant differences between batches of kits with respect to radiochemical purity (RCP) or image quality. Up to 3000 MBq (81 mCi) pertechnetate could be added to the kit without adversely affecting RCP or image quality. It was shown that image quality was directly affected by RCP at time of injection and dropped sharply when RCP fell below 85%. Interstitial injection and mixing with blood prior to injection also resulted in poor image quality. Pretreatment with perchlorate reduced uptake of activity in the parotid glands; this improved image quality and reduced the influence of RCP.

Brain↗

Comparison of left ventricular function and myocardial perfusion for evaluating perioperative cardiac risk of abdominal aortic surgery.

The measurement of left ventricular function by gated blood pool scanning and of myocardial perfusion by dipyridamole thallium imaging were compared in a prospective study of patients who had abdominal aortic aneurysm or aortoiliac occlusive disease to determine which measurement was the better predictor of postoperative cardiac complications. Sixty-six men and 19 women (mean age 67 years) underwent both tests before admission for surgery. Fifty-six had repair of an abdominal aortic aneurysm, and 29 had reconstruction for aortoiliac occlusive disease. In 17 patients the left ventricular ejection fraction was less than 50%. Dipyridamole thallium imaging was positive, showing redistribution, in 45 patients. Postoperative cardiac complications occurred in 33 patients. The sensitivity of dipyridamole thallium imaging (91%) was significantly (p less than 0.01) greater than that observed with gated blood pool scanning (27%). However, the specificity of gated blood pool scanning (85%) was similar to that of dipyridamole thallium imaging (71%). Diagnostic accuracy was greatest with dipyridamole thallium imaging (79% versus 62% [p less than 0.02]). Dipyridamole thallium imaging is superior to gated blood pool scanning for perioperative evaluation of vascular surgical patients.

Aged↗

Technetium-99m spiperone dithiocarbamate: a potential radiopharmaceutical for dopamine receptor imaging with SPECT.

Spiperone dithiocarbamate (SPDC) was prepared by reacting spiperone with carbon disulfide followed by sodium hydroxide. SPDC was labelled with 99mTc by reduction of pertechnetate with formamidine sulfinic acid or sodium dithionite at alkaline pH, resulting in approximately 40% incorporation of 99mTc. The lipophilic complex was conveniently isolated at high specific activity and high radiochemical purity by extraction into dichloromethane, which was then evaporated and the residue was redissolved in a 1:3 mixture of ethanol and saline containing 0.1 mg/mL gentisic acid. Biodistribution studies following i.p. injection in rats showed low uptake of radioactivity in the brain, but striatum/cortex and striatum/cerebellum ratios were reduced by pretreatment with haloperidol. This agent may allow imaging of dopamine D-2 receptors using single-photon emission computed tomography (SPECT).

Animals↗

Routine determination of radiochemical purity of 99mTc-MIBI.

The manufacturer recommends that the radiochemical purity of 99mTc-MIBI be determined with alumina TLC plates developed in ethanol, but for routine use this is slow and requires care. After comparing a variety of systems, we obtained equivalent results using ITLC-SG strips developed with saline to determine [99mTc]pertechnetate and with acetone to determine 99mTc colloid; % 99mTc-MIBI was determined by difference from 100%. These separations are the opposite of those obtained with the routine polar 99mTc radiopharmaceuticals. Equivalent results were obtained even more rapidly by extracting 99mTc-MIBI from water into chloroform.

Chromatography, Thin Layer↗

Technetium-99m dithiocarbamates as potential brain agents: evaluation of aliphatic and amine-containing analogues.

Technetium-99m forms a lipophilic complex with diethyldithiocarbamate (DDC) but this complex is not retained in the brain as is thallium-201 DDC. We therefore prepared a series of aliphatic and amine-containing analogues of DDC and evaluated the properties of their 99mTc complexes in vitro and in vivo. The ethyl acetate/buffer partition coefficients of the amine-containing derivatives showed a response to pH. Four of the five complexes were less stable than DDC in vitro and showed greater retention in rabbit brain. These agents warrant further investigation for cerebral perfusion imaging with SPECT.

Animals↗

Clinical use of technetium-99m HM-PAO for determination of brain death.

We report our clinical experience with the use of [99mTc]hexamethyl propyleneamine oxime (HM-PAO) in establishing a diagnosis of brain death in 11 patients following trauma to the head and four patients who suffered atraumatic injuries. In 9/15 studies there was no intracranial flow present and brain death was then confirmed by standard criteria. Of the remaining 6/15 studies which showed evidence of cerebral perfusion, 3/6 patients underwent a subsequent HM-PAO study which showed cessation of perfusion. One additional patient died of pneumonia and two patients survived. Thus, in all cases where there was no flow present the diagnosis of brain death was later confirmed whereas three patients clinically thought to be brain dead showed significant perfusion and survived the cerebral trauma. HM-PAO may be useful in determination of brain death because it provides unequivocal results, can be performed by planar imaging at the bedside, and does not require withdrawal of medical therapy, thus allowing a diagnosis to be established more rapidly.

Brain↗

Stabilization of stannous pyrophosphate kits with gentisic acid.

We evaluated the ability of gentisic acid, an antioxidant, to stabilize stannous pyrophosphate (Sn:PPi) kits and extend the shelf-life of the kit after reconstitution. In vitro studies showed that gentisic acid (0.5 mg/mL) stabilized the stannous ion against oxidation by various levels of exogenous hydrogen peroxide. In patients who received stabilized Sn:PPi for in vivo red blood cell labelling, the left ventricle-to-background activity ratio was significantly higher than that in patients who received a standard formation of Sn:PPi. Gentisic acid is now used routinely in the Sn:PPi kit formulation in this institution.

Drug Stability↗

Technetium-99m red blood cell labeling in patients treated with doxorubicin.

Radionuclide angiography is useful in monitoring cardiotoxicity of doxorubicin, but in vivo RBC labeling in these patients is believed to be poorer than that in general patients. The left ventricle-to-background activity ratio (R) was not significantly lower in patients treated with doxorubicin (3.24 +/- 1.15, N = 13) than in control patients (3.89 +/- 1.60, N = 14). With both modified in vivo and in vitro labeling, R was significantly improved in patients treated with doxorubicin (4.37 +/- 0.91, N = 8, and 4.37 +/- 1.22, N = 13, respectively). However, with the modified in vivo method, labeling efficiency remained a function of hematocrit, whereas the in vitro method removed this dependency. Both modified in vivo and in vitro labeling result in improved image quality over in vivo labeling in patients treated with doxorubicin, and the choice of method can be based on other factors.

Doxorubicin↗

Technetium-99m HM-PAO stereoisomers: differences in interaction with glutathione.

[99mTc]HM-PAO exists as two stereoisomers, d,1 and meso, only one of which is retained in the brain. It has been suggested recently that the biodistribution of [99mTc]d,1-HM-PAO can be explained by its interaction with glutathione (GSH) in the tissues. We studied the interactions of the d,1 and meso isomers with GSH in vitro by measuring the partitioning of activity between ethyl acetate and aqueous GSH solutions at various concentrations. Partitioning of both isomers demonstrated a sigmoidal relationship with GSH concentration, but the d,1 isomer showed eightfold greater reactivity than the meso isomer. In a separate experiment, the d,1 isomer showed a sevenfold greater interaction rate with GSH than the meso isomer. These results suggest that the stereoisomers of [99mTC]HM-PAO show differences in their interaction rate with GSH which may explain their different retention in the brain.

Glutathione↗