technetium-tc-99m-exametazime and cobaltous-chloride

This present study was carried out to investigate whether stabilization of Tc-99m-HMPAO with methylene blue (MB) or cobalt chloride (CC) causes a sensible improvement in image quality and how cerebral to noncerebral activity ratios compare with those of Tc-99m-ECD.. 30 minutes after preparation 400-600 MBq unstabilized Tc-99m-HMPAO (N = 35 patients), Tc-99m-HMPAO added with MB (N = 24 patients), added with CC (N = 30 patients) or Tc-99m-ECD (N = 28 patients) were injected. Radiochemical stability was measured in vitro with three chromatographical methods. Image quality was assessed quantitatively using two ratios, one of them determined by count densities of brain/scalp (Os), the other one by count densities of brain/nose (QN). In addition, image quality (0 = bad, 3 = excellent) and background activity (0 = high, 3 = no) were visually assessed by three independent observers.. In contrast to unstabilized Tc-99m-HMPAO the integrity of the complexes of MB-Tc-99m-HMPAO, CC-Tc-99m-HMPAO and Tc-99m-ECD decreased only by a few percent during a period of 2 hours after reconstitution (66.8 +/- 9.9 vs. 93.0 +/- 2.5, 91.8 +/- 1.9 and 96.9 +/- 1.4%, p < 0.001). Qs and Qn (m.v. +/- SD) differed significantly between studies using unstabilized Tc-99m-HMPAO (3.0 +/- 0.4 and 2.1 +/- 0.3), MB-Tc-99m-HMPAO (3.4 +/- 0.4 and 2.3 +/- 0.3), CC-Tc-99m-HMPAO (3.6 +/- 0.6 and 2.6 +/- 0.4) and those using Tc-99m-ECD (4.3 +/- 0.7 and 4.8 +/- 1.4, p < 0.05 and < 0.001). Stabilization with CC or MB resulted in significant higher scoring of image quality and lower scoring of background activity in comparison to that of unstabilized Tc-99m-HMPAO, without reaching the scores obtained with Tc-99m-ECD.. It is concluded that stabilization of Tc-99m-HMPAO with MB or CC definitely improves image quality in rCBF-SPECT, without reaching that of Tc-99m-ECD. Improvement of image quality results from the reduction of the amount of decomposition products that contribute to considerable extracerebral activity.

Topics: Adult; Aged; Aged, 80 and over; Brain; Cerebrovascular Disorders; Cobalt; Cysteine; Depression; Drug Stability; Female; Humans; Male; Methylene Blue; Middle Aged; Neurodegenerative Diseases; Organotechnetium Compounds; Radiopharmaceuticals; Scalp; Sensitivity and Specificity; Sleep Apnea Syndromes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The method described by Weisner et al. for stabilizing 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) with cobalt chloride hexahydrate solution is the most promising developed to date. The aim of our work was to study the behaviour of cobalt during the labelling of leukocytes with 99Tcm-HMPAO stabilized in vitro using this method. Three parallel labellings were carried out using six blood samples taken from polycythaemic patients. The first set of labellings was performed using 99Tcm-HMPAO, the second set using 99Tcm-HMPAO stabilized with cobalt chloride hexahydrate solution "spiked' with 57Co-chloride, and the third set using 57Co-chloride solution alone. Measurements of radioactivity content were made on the leukocyte pellets after washing at five time points post-labelling (t = 0, 30 min, 1 h, 2 h and 4 h). The data show that leukocytes do not retain cobalt during labelling with stabilized 99Tcm-HMPAO. Studies carried out in parallel demonstrated that the presence of cobalt in the cell-labelling medium had no effect on cell viability.

Topics: Analysis of Variance; Cell Survival; Cobalt; Cobalt Radioisotopes; Drug Carriers; Drug Stability; Female; Humans; In Vitro Techniques; Leukocytes; Male; Organotechnetium Compounds; Oximes; Polycythemia; Radionuclide Imaging; Technetium Tc 99m Exametazime

It has been reported that the stability of a 1.11-GBq (30 mCi) technetium-99m d,l-hexamethyl-propylene amine oxime (HMPAO) preparation can be improved to up to 5 h by the addition of 200 micrograms CoCl2.6H2O within 2 min after reconstitution. However, it is not clear whether this method is also efficient for high-activity preparations (5.55 GBq) and whether this modified 99mTc-d,l-HMPAO has the same biological properties and can safely be used. We have now studied CoCl2-stabilised 99mTc-d,l-HMPAO preparations containing different amounts of "in-house" HMPAO ligand and SnCl2 and reconstituted with activities from 1.11 GBq to 5.55 GBq 99mTc. The characteristics of the generator eluates were also divergent, ranging from fresh eluates from a generator eluted less than 2 h previously to 4-h-old eluates from a generator not eluted during the preceding 72 h. Preparations containing up to 5.55 GBq 99mTc and as low as 2 micrograms SnCl2.2H2O can be efficiently stabilised for at least 6 h by the addition of CoCl2 shortly after reconstitution. Interestingly, it was found that the stabilisation method is not efficient if the cobalt ions are added prior to reconstitution of the preparation. This implies that the cobalt chloride cannot be incorporated in the labelling kit. Also, preparations with amounts of the ligand lower or higher than 0.5 mg formed the 99mTc-d,l-HMPAO complex with low radiochemical yield or showed rapid degradation. Therefore, combination of a subdivision and storage of Ceretec kits in fractions (as reported in the literature) is contra-indicated with this CoCl2 stabilisation method. CoCl2-stabilised Ceretec kits reconstituted with 5550 MBq 99mTcO4- and used 4-5 h after preparation retain the diagnostic usefulness of the fresh 1110-MBq preparation with regard to leucocyte labelling and brain imaging. Although baboon brain uptake of the stabilised preparation was 6%-9% lower, this small difference could not be distinguished in the tomographic images. The data obtained with both inhouse prepared d,l-HMPAO and Ceretec kits suggest that the eluate restrictions recommended by the Ceretec manufacturer can be neglected if the preparation is stabilised with Co2+ ions. Studies with 57Co-spiked CoCl2 added to d,l-HMPAO preparations demonstrated that the Co2+ ions clearly interact with the d,l-HMPAO ligand, probably to form one or more complexes. From biodistribution studies in mice it became evident that the toxicological profile of the Co2+ ions in the pre

Topics: Animals; Brain; Cobalt; Drug Stability; Erythrocytes; Humans; Male; Mice; Organotechnetium Compounds; Oximes; Papio; Radionuclide Imaging; Reagent Kits, Diagnostic; Technetium Tc 99m Exametazime; Time Factors; Tissue Distribution

A protocol has been devised to effectively extend the limited post-reconstitution shelf life of technetium-99m exametazime as a radiopharmaceutical for imaging cerebral blood flow (CBF) distribution. The potential of 99mTc-exametazime stabilised with cobalt chloride for imaging CBF distribution as late as 4 h after reconstitution has been examined in ischaemic and non-ischaemic tissue in halothane-anaesthetised cats. Focal cerebral ischaemia was produced by permanent middle cerebral artery occlusion. The relationship between 99mTc-exametazime uptake and retention and CBF (assessed with [14C]iodoantipyrine 10 min after first radiopharmaceutical administration) was determined in the same tissue section with double label autoradiography. Over the CBF range 0-80 ml 100 g-1 min-1, the uptake of 99mTc-exametazime (quantitatively and topographically) was linearly related to CBF irrespective of whether the 99mTc-labelled tracer was unstabilised (and administered within 10 min of reconstitution) or was stabilised with cobalt chloride (and administered up to 240 min after reconstitution). For levels of CBF in excess of 80 ml 100 g-1 min-1 the excellent topographical relationship between 99mTc-exametazime distribution and CBF is maintained but quantitatively, 99mTc-exametazime underestimates CBF to a similar degree in animals receiving stabilised and unstabilised 99mTc-exametazime. The presence of the stabiliser, cobalt chloride, extends greatly the period over which 99mTc-exametazime can be used after reconstitution to generate images of CBF distribution in normal and ischaemic cerebral tissue.

Topics: Animals; Brain; Brain Ischemia; Cats; Cerebrovascular Circulation; Cobalt; Drug Stability; Organotechnetium Compounds; Oximes; Reagent Kits, Diagnostic; Technetium Tc 99m Exametazime; Time Factors; Tomography, Emission-Computed, Single-Photon