Influence of Storage Temperature on Radiochemical Purity of 99mTc-Radiopharmaceuticals.

The influence of effective room temperature on the radiochemical purity of 99mTc-radiopharmaceuticals was reported. This study was born from the observation that in the isolators used for the preparation of the 99mTc-radiopharmaceuticals the temperatures can be higher than those reported in the commercial illustrative leaflets of the kits. This is due, in particular, to the small size of the work area, the presence of instruments for heating, the continuous activation of air filtration, in addition to the fact that the environment of the isolator used for the 99mTc-radiopharmaceuticals preparation and storage is completely isolated and not conditioned. A total of 244 99mTc-radiopharmaceutical preparations (seven different types) have been tested and the radiochemical purity was checked at the end of preparation and until the expiry time. Moreover, we found that the mean temperature into the isolator was significantly higher than 25 °C, the temperature, in general, required for the preparation and storage of 99mTc-radiopharmaceuticals. Results confirmed the radiochemical stability of radiopharmaceutical products. However, as required in the field of quality assurance, the impact that different conditions than those required by the manufacturer on the radiopharmaceuticals quality have to be verified before human administration.

Impurity profiling of N,N'-ethylenebis-l-cysteine diethyl ester (Bicisate).

A HPLC-UV-CAD method with a HILIC column for impurity profiling of the 99mTc chelating agent bicisate has been developed and evaluated. Bicisate and its impurities were separated by means of isocratic elution on a zwitterionic stationary phase using a mixture of 7.5mmol/L trifluoroacetic acid and acetonitrile (47.5:52.5 V/V) as the mobile phase. Five different bicisate batches of a manufacturer were tested using the method. In addition LC-MS experiments were conducted in order to identify the impurities. The predominant impurities found were the oxidation product (disulfide), the monoester of ethylene dicysteine and an unknown compound with an m/z of 293 in ESI positive mode. A new degradation product of bicisate, bicisate lactam, was identified during sample solution stability assessment.

Nationwide Laboratory Adherence to Myocardial Perfusion Imaging Radiation Dose Reduction Practices: A Report From the Intersocietal Accreditation Commission Data Repository.

OBJECTIVES: This study sought to examine current laboratory practices for radiation effective doses for myocardial perfusion imaging (MPI) and laboratory adherence to guideline-directed radiation reduction practices. BACKGROUND: A recent focus on radiation dose reduction for cardiovascular imaging has led to several published guidelines and consensus statements detailing performance metrics for laboratory practices. We sought to examine laboratory adherence to optimized radiation dose protocol recommendations among 5,216 submitted cases from 1,074 MPI laboratories evaluated for Intersocietal Accreditation Commission accreditation. METHODS: Eligible imaging centers included MPI laboratories enrolled in the Intersocietal Accreditation Commission data repository of accreditation applications from 2012 to 2013. Accreditation requires submission of 3 to 5 cases for evaluation of a range of representative cases. Based on standard dosimetry for rest and stress MPI, an effective dose (in millisieverts) was calculated. Model simulations were performed to estimate guideline-directed effective doses. RESULTS: The average effective dose was 14.9 ± 5.8 mSv (range 1.4 to 42.4 mSv). A 1-day technetium Tc 99m protocol was used in 82.9% of cases, whereas a 2-day technetium Tc 99m and dual isotope protocol was used in 7.5% of submitted cases. Only 1.5% of participating imaging centers met current guidelines for an average laboratory radiation exposure ≤9 mSv, whereas 10.1% of patient effective doses were >20.0 mSv. A model simulation replacing the radiation exposure of dual isotope MPI with that of a 1-day technetium Tc 99m protocol reduced the proportion of patients receiving an effective dose >20 mSv to only 2.7% of cases (p < 0.0001). CONCLUSIONS: Mandatory laboratory accreditation for MPI allows for examination of current radiation dosimetry practices. Current guidelines for reduced patient-specific radiation exposure are rarely implemented, with few laboratories meeting recommendations of ≤9 mSv for 50% of patients. Increased educational efforts and the development of performance measures for laboratory accreditation may be required to meet current radiation dose-reduction standards.

Single vial freeze-dried TRODAT-1 kit: preparation and demonstration of clinical efficacy of [(99m)Tc]TRODAT-1 in Indian scenario.

A single vial freeze-dried kit formulation for preparation of three patients' dose of [(99m)Tc]TRODAT-1 has been developed for early diagnosis of Parkinson's disease (PD). Kits were evaluated to ascertain the purity, stability and batch to batch variations. Preclinical evaluation was carried out in laboratory animals and clinical imaging was performed in human patients with PD. The labeling yield and purity of [(99m)Tc]TRODAT-1 was >90%. Swiss mice showed retention of [(99m)Tc]TRODAT-1 in the mid brain region. Clinical studies showed decreased striatal uptake with increasing severity of PD.

Direct determination of ECD in ECD Kit: a solid sample quantitation method for active pharmaceutical ingredient in drug product.

Technetium-99m ethyl cysteinate dimer (Tc-99m-ECD) is an essential imaging agent used in evaluating the regional cerebral blood flow in patients with cerebrovascular diseases. Determination of active pharmaceutical ingredient, that is, L-Cysteine, N, N'-1,2-ethanediylbis-, diethyl ester, dihydrochloride (ECD) in ECD Kit is a relevant requirement for the pharmaceutical quality control in processes of mass fabrication. We here presented a direct solid sample determination method of ECD in ECD Kit without sample dissolution to avoid the rapid degradation of ECD. An elemental analyzer equipped with a nondispersive infrared detector and a calibration curve of coal standard was used for the quantitation of sulfur in ECD Kit. No significant matrix effect was found. The peak area of coal standard against the amount of sulfur was linear over the range of 0.03-0.10 mg, with a correlation coefficient (r) of 0.9993. Method validation parameters were achieved to demonstrate the potential of this method.

A rapid radiochemical purity testing method for 99mTc-tetrofosmin.

UNLABELLED: The standard radiochemical purity (RCP) testing method for (99m)Tc-tetrofosmin as described in the package insert requires extensive time (20-30 min) and considerable skill to achieve accurate results. Additionally, the instant thin-layer chromatography strip impregnated with silica gel (2x20 cm) used in the standard method will not be commercially available in the future. The purpose of this study was to evaluate whether a method developed by our laboratory for RCP testing of (99m)Tc-sestamibi could also be used as an alternative method for the RCP assay of (99m)Tc-tetrofosmin. METHODS: The alternative RCP testing system consisted of a precut paper strip (1x8.5 cm) from solvent saturation pads (Pall Corp.) as the stationary phase, with 1:1 chloroform:tetrahydrofuran used as the mobile phase. To validate the reliability of the alternative method, RCP values from 17 kit preparations were compared with the 2 methods. Kits were reconstituted according to the package insert instructions, and 4 additions of (99m)Tc-sodium pertechnetate were purposely added to create trials with RCP values below the accepted limit of 90% purity. RESULTS: Two hundred four trials (100 of which were replicated) were run from the 17 kit preparations. Sixty-four (31%) of the 204 trials were below 90% purity based on the standard method. The overall agreement between the standard and alternative methods was 94% (192/204). The sensitivity of the alternative method for unacceptable RCP limits was 86% (55/64), and the specificity for acceptable RCP values was 98% (137/140). The agreement between the replicated trials of the alternative method was 99% (99/100), and for the standard method it was 92% (92/100). CONCLUSION: The standard method proved to be a much slower method and requires much more precision and attention. The alternative method is much faster, is easier, requires less attention to the solvent-development process, and can be used for RCP testing of both (99m)Tc-tetrofosmin and (99m)Tc-sestamibi. Furthermore, the stationary phase is much more readily available, is not moisture-sensitive, and is less susceptible to operator technique. Our method is accurate in determining the RCP value of (99m)Tc-tetrofosmin and is a better RCP testing method for (99m)Tc-tetrofosmin.

Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry.

OBJECTIVES: Three accumulative tracers, iodine-123-labeled N-isopropyl-p-iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dimer (Tc-99m-ECD) are widely used to measure cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). In the present study, normal regional distribution of CBF measured with three different SPECT tracers was entered into a database and compared with regional distribution of CBF measured by positron emission tomography (PET) with H2(15)O. The regional distribution of tissue fractions of gray matter determined by voxel-based morphometry was also compared with SPECT and PET CBF distributions. METHODS: SPECT studies with I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively. PET studies were performed on 11 healthy subjects. Magnetic resonance (MR) imaging studies for voxel-based morphometry were performed on 43 of the 48 subjects who underwent SPECT study. All SPECT, PET, and MR images were transformed into the standard brain format with the SPM2 system. The voxel values of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray matter, white matter, and cerebrospinal fluid images were segmented and extracted from all transformed MR images by applying voxel-based morphometry methods with the SPM2 system. RESULTS: Regional distribution of all three SPECT tracers differed from that of H2150 in the pons, midbrain, thalamus, putamen, parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital cortex. No significant correlations were observed between the tissue fraction of gray matter and CBF with any tracer. CONCLUSION: Differences in regional distribution of SPECT tracers were considered to be caused mainly by differences in the mechanism of retention of tracers in the brain. Regional distribution of CBF was independent of regional distribution of gray matter fractions, and consequently the blood flow per gray matter volume differed for each brain region.

Characterization and quality control analysis of 99mTc-bicisate.

The aim of this study was to investigate the mini cartridge versus paper chromatography quality control methods for determining the radiochemical purity (RCP) of (99m)Tc-bicisate. The 4 methods that were compared with the manufacturer's method included Whatman 17 paper/ethyl acetate solvent, instant thin-layer chromatography (ITLC) silica gel paper/saline solvent, reverse-phase C18 mini cartridge/saline solvent, and strong anion exchange mini cartridge/water solvent. At 30 min after reconstitution, (99m)Tc-bicisate was formed at 97%-98% RCP as assayed by the paper and cartridge methods, and the strong anion exchange/water for injection (WFI) system slightly underestimated the percentage at 96%. A significantly lower RCP was obtained for the C18/saline method when a faster flow rate was used. The lipophilic complex moved with ethyl acetate on Whatman 17, was separated from origin impurities on ITLC silica gel/saline, and remained on the column with C18/saline. For strong anion exchange/WFI, components in the radioactive formulation are likely to have influenced the percentage of (99m)Tc-bicisate. The time disadvantage for ITLC silica gel/saline analysis made the method less than ideal. The C18 mini cartridge/saline method was found to be the simplest and fastest; a result was obtained in 2 min with use of a safe solvent of elution.

A better method of quality control for 99mTc-tetrofosmin.

UNLABELLED: The method of quality control (QC) described on the package insert for (99m)Tc-tetrofosmin requires meticulous attention to technique for accurate radiochemical purity results. About 30 min are needed. Other proposed methods have been validated only with pertechnetate. We developed a convenient new method using silica cartridges. METHODS: A silica cartridge with 70:30 methanol:water was determined to be acceptable. The method was validated against sodium pertechnetate ((99m)TcO(4)), (99m)Tc-glucoheptonate, (99m)Tc-sulfur colloid, and low-purity (99m)Tc-tetrofosmin. The validations were made by using a small volume of concentrated (99m)TcO(4) with expired kits. Instant thin-layer chromatography (ITLC) showed 6 impurities after an hour or two. The effects of sample size and flow rate were determined. The precision of repeated tests was determined by comparison with the results of 8 replications on the same batch. The 2 methods were compared at a hospital and at 2 commercial nuclear pharmacies, for a total of 134 replications, with 21 preparations being of <90% radiochemical purity. RESULTS: Volumes between 25 and 100 micro L did not affect the silica-cartridge method but did affect the ITLC method. Flow rate is critical and must be < or =5 mL/min with the silica cartridges. The SD and variance by ITLC were 7 and 51 times larger, respectively. Using the package insert technique as the gold standard, all batches of <90% radiochemical purity were rejected and those of >90% radiochemical purity were accepted. Linear regression gave the following equation: ITLC = 1.0051 x silica cartridge (R = 0.99). One- and 2-binned chi(2) analyses gave P values > 0.999999. A 2 x 2 contingency table showed 100% sensitivity, accuracy, and specificity, with a Fisher's exact test P value of 5.7 x 10(-25). Correlation was nearly perfect. CONCLUSION: According to the published rating criteria for alternate radiochemical purity tests (American Pharmacists' Association), the silica-cartridge method has a score of 90.2, versus 65.8 for ITLC. On the basis of published criteria for alternate radiochemical purity testing methods, the new method is clearly seen to be superior. Furthermore, alternate methods were validated only with free (99m)TcO(4) and colloidal impurities. We showed that these are not the significant radiochemical impurities with (99m)Tc-tetrofosmin and that those methods are not valid. This new method is fast, convenient, accurate, safe, and economical, but careful control of flow rate is required.

99mTc-Labeling of a hydrazinonicotinamide-conjugated LTB(4) receptor antagonist useful for imaging infection and inflammation.

This report describes the (99m)Tc labeling of a hydrazinonicotinamide (HYNIC)-conjugated LTB(4) receptor antagonist (SG380). The ternary ligand technetium complex [(99m)Tc(SG38)(tricine)(TPPTS)] (RP517) was prepared using a non-SnCl(2)-containing formulation ((2001) J. Pharm. Sci. 90, 114-123). Unlike other HYNIC-conjugated small biomolecules, SG380 is lipophilic and has low solubility in the kit matrix. Using a combination of a solubilizing agent (Lysolecithin) and a cosolvent (ethanol), we have developed a new formulation for routine preparation of RP517. Using this formulation, RP517 can be prepared in high radiochemical purity (RCP > 90%) and remains stable in the kit matrix for at least 6 h. We also prepared the corresponding (99)Tc analogue, [(99)Tc]RP517. An HPLC concordance experiment using RP517 and [(99)Tc]RP517 showed that the same technetium complex was prepared at both the tracer and macroscopic levels. The LC-MS data are completely consistent with the 1:1:1:1 composition for Tc:SG380:tricine:TPPTS.

Rapid quality control for testing the radiochemical purity of 99Tc(m)-tetrofosmin.

We describe a new thin-layer chromatography (TLC) method to evaluate the radiochemical purity of 99Tc(m)-tetrofosmin without the drawbacks of toxicity, solvent ratios and time requirement associated with the standard TLC method. The new method uses miniaturized instant TLC plates impregnated with silica gel (ITLCTM/SG, 2.5 x 10 cm) for the stationary phase and 2-butanone for the mobile phase. The standard TLC method was performed with ITLCTM/SG plates (5 x 20 cm) and dichloromethane/acetone (65:35, v/v). Thirty five preparations were analysed by both methods with a storage phosphor imaging system to determine the percentages of hydrolyzed-reduced 99Tc(m) compound (99Tc(m)O2), 99Tc(m)-tetrofosmin and free 99Tc(m)-pertechnetate (99Tc(m)O4(-)). Using the miniaturized TLC method, 99Tc(m)-tetrofosmin had a mean Rf value of 0.55 (standard deviation, 0.05), while 99Tc(m)O4(-) migrated with the solvent front (Rf=1) and 99Tc(m)O2 remained at the origin of the strips (Rf=0). No significant difference was found between miniaturized and standard TLC methods for the radiochemical purity of 99Tc(m)-tetrofosmin using the Wilcoxon matched-pair signed-rank test (P=0.82). Furthermore, the two methods showed a good correlation as measured by the Spearman rank coefficient (r=0.89) and were in perfect agreement, with a kappa index of +1, for a cut-point between positive and negative set at 90%. In conclusion, the results indicate that the miniaturized TLC method is effective for the routine evaluation of the radiochemical purity of 99Tc(m)-tetrofosmin, without some of the drawbacks of the standard method.

Radiochemical purity of routinely prepared 99Tcm radiopharmaceuticals: a retrospective study.

Radiochemical purity is an important quality parameter for radiopharmaceuticals. In this study, the radiochemical purity of 2090 samples out of 7000 routine preparations of 20 different 99Tcm radiopharmaceuticals was tested using standard methods over a period of more than 7 years. The mean radiochemical purity was 96.92% (standard deviation = 6.71%). Seventy-four preparations failed to meet radiochemical purity limits; that is, 3.54% of all preparations tested or 1.06% of all preparations in the observation period. The reasons for substandard preparations were mainly related to laboratory-specific conditions. The introduction of a dedicated quality control protocol allowed the elimination of many sources of labelling failures and could reduce the number of administered preparations with an insufficient radiochemical purity. We stress the need for quality control in the preparation of radiopharmaceuticals and provide original radiochemical purity values of routinely prepared 99Tcm radiopharmaceuticals.

An alternative to the reference method for testing the radiochemical purity of 99Tcm-tetrofosmin.

The recommended method for controlling the radiochemical purity (RCP) of 99Tcm-labelled tetrofosmin is thin-layer chromatography (TLC) with silica gel as the stationary phase and acetone:dichloromethane (35:65, v/v) as the mobile phase. However, this test is time-consuming and uses a toxic substance. We propose an alternative method to control RCP, based on a solid-phase extraction method (SPE) using a Sep Pak C18 cartridge. We used both methods to analyse 35 samples and to determine the percentages of colloid, radiopharmaceutical and free 99Tcm-pertechnetate. Normal labelling processes were modified to obtain a wide range of values. The range of RCP values obtained was 63.4-96.5% (median = 93.8%) by the standard TLC method and 70.1-96.4% (median = 94.1%) by the SPE method. A significant difference was observed only for the percentage of free 99Tcm-pertechnetate (P < 0.05). The agreement between the two methods, using 90% RCP as the limit, gave a kappa index = +1 (P < 0.001), indicating total agreement between them. The proposed method is useful to control RCP because it yields results that are in good agreement with those of the standard method, and because it is safer and less time-consuming.

Artefacts in the thin-layer chromatographic analysis of 99Tcm-tetrofosmin injections.

In an evaluation of techniques for dispensing 99Tcm-tetrofosmin injections, variability in radiochemical purity measured by the recommended 'cut-and-count' thin-layer chromatographic (TLC) analytical technique was observed. This was due to inconsistency in the position of the 99Tcm-tetrofosmin on the chromatography plate. An investigation was therefore undertaken to identify the factors which influence the Rf value of 99Tcm-tetrofosmin and the subsequent effect on the values obtained in the measurement of radiochemical purity. TLC was performed on an ITLC/SG stationary phase with a mobile phase of dichloromethane:acetone (65:35). On a satisfactory chromatogram, the main peak had an Rf of approximately 0.5 and the radiochemical purity was measured at > 90%. The Rf of the main peak and the measured radiochemical purity were found to increase as the size of the sample applied to the plate was increased. Force-drying the sample spot after application to the TLC plate gave a single peak with an Rf of 0. The dimensions of the tank and the time allowed for mobile phase saturation did not affect the outcome of the analysis. Small variations in the composition of the mobile phase affected the Rf of the main peak but not the measured radiochemical purity. TLC plates that were dried at 11 degrees C before use were found to give distorted chromatograms and unreliable measurements of radiochemical purity. In conclusion, when using TLC to measure the radiochemical purity of 99Tcm-tetrofosmin, the following precautions should be observed: (1) the sample spot applied to the TLC plate should be in the range 10-20 microliters; (2) the spot should not be force-dried with air; and (3) ITLC/SG plates should not be dried before use.

[An alternative method to determine the radiochemical purity of the 99mTC-tetrofosmine preparations]. / Un método alternativo para determinar la pureza radioquímica de las preparaciones de 99mTc-Tetrofosmina.

This paper describes a new quality control method to determine the radiochemical purity (RCP) value of Technetium-99m-Tetrofosmin preparations. The results of this procedure were compared with the results obtained with the method suggested by the manufacturer of the kit (classic method), consisting in thin-layer chromatography involving the use of a single strip of ITLC/SG as the stationary phase, and a acetone:dichlorometane 35:65 (Ac:DCM) solvent mixture as the mobile phase. The method that is proposed in this paper (alternative method) uses the same stationary phase but it is developed in a single solvent, methylethylketone (MEK). This method has the following advantages: a better capacity to separate the 99mTc-Tetrofosmin complex from 99mTcO4- and 99mTcO2 impurities, a faster chromatographic developing time and the use of a single solvent in the quality control.

Technetium-99m radiopharmaceutical preparation problems: 12 years of experience.

OBJECTIVE: Chemical reactions involved in preparing 99mTc radiopharmaceuticals occasionally result in products of substandard purity. A retrospective examination of preparation problems that occurred in the author's institution was conducted to better define the incidence, recognize patterns and identify causes of substandard 99mTc radiopharmaceutical products. METHODS: All 99mTc radiopharmaceutical preparation and quality control testing records for the years 1986-1997 were reviewed, and preparation factors associated with substandard products were identified and examined. RESULTS: Fifty of 20,972 (0.2%) 99mTc products had substandard radiochemical purity; none were administered to patients. Twenty-eight of the 50 substandard products (56%) involved macroaggregated albumin with the remainder divided among in vitro red blood cells, exametazime, disofenin, sestamibi, mertiatide and sulfur colloid. Thirty-three of the 50 (66%) involved 99mTc-pertechnetate obtained as the first elution of a new generator and/or 99mTc-pertechnetate more than 12 hr old. Several of the substandard products involved other preparation factors and/or human error. CONCLUSION: The majority of substandard 99mTc radiopharmaceutical products involved the use of 99mTc-pertechnetate containing excessive amounts of 99Tc and/or oxidizing impurities to prepare products containing relatively small amounts of stannous. Although substandard products are an infrequent occurrence, radiochemical purity testing should be performed routinely on all 99mTc radiopharmaceuticals before patient administration.

Modified preparation and rapid quality control test for technetium-99m-tetrofosmin.

OBJECTIVE: The objectives of this study were to: modify the preparation of 99mTc-tetrofosmin by using twice the amount of 99mTcO4- recommended by the manufacturer; evaluate the use of miniaturized rapid paper chromatography (MRPC) for quality control (QC) testing; and determine the in vitro stability of the modified preparation using MRPC. METHODS: Two preparations of 99mTc-tetrofosmin were made: one with 4.4-8.8 GBq (120-240 mCi) and the other with 13.9-17.6 GBq (380-480 mCi) 99mTcO4-, referred to as regular and modified preparations, respectively. Routine QC tests were performed using MRPC and instant thin-layer chromatography/silica-gel (ITLC/SG) systems. The preparations were injected into 58 patients. Planar and SPECT images of stress and rest studies were obtained. The technical quality of the SPECT images was graded visually by four observers. Heart-to-lung and heart-to-background ratios were calculated from the planar images. RESULTS: The QC testing procedure took 4.18 +/- 0.15 min with MRPC and 54 +/- 5.3 min with ITLC/SG systems. The percent labeling efficiency, as determined by both techniques, ranged from 95.6 +/- 1.6 to 97.2% +/- 0.8%. Both preparations were stable up to 6 hr after reconstitution. There was no difference between the cardiac-to-lung and cardiac-to-background ratios of the two preparations. CONCLUSION: The results indicate that MRPC is a faster and effective chromatographic technique for routine QC testing of 99mTc-tetrofosmin. Doubling the amount of 99mTcO4- used in preparing 99mTc-tetrofosmin did not affect its in vitro stability, its efficacious use in patients or the technical quality of the images.

Radiochemical purity testing for 99Tcm-exametazime: a comparison study for three-paper chromatography.

The standard radiochemical purity (RCP) determination uses a three-paper chromatography strip and solvent system (TP). The involvement of multiple strips for calculation of percentage primary, lipophilic 99Tcm-exametazime complex is tedious and time-consuming. The significant streaking of radioactivity on the ITLC/SG MEK strip of the TP method indicates that ITLC/SG MEK may not be an ideal system for RCP analysis of 99Tcm-exametazime. This study was undertaken to compare the standard TP method with two other proposed single-strip chromatography systems: Whatman 17 Chr paper with ethyl acetate (WE) and Gelman Solvent Saturation Pads paper with ether (GE). Our results showed that the solvent developing times (n = 55) and Rf values for TP, WE and GE were 130.4 +/- 9.0 s/0.5-1.0, 205.9 +/- 13.0 s/0.2-1.0 and 90.2 +/- 7.5 s/0.8-1.0, respectively. For RCP values ranging from 45.0 to 94.6% (n = 61), both WE and GE closely correlated with TP (r = 0.97 and 0.96). However, in the intermediate RCP range (i.e. 75-85%, n = 25), the false RCP acceptance rate (i.e. RCP > or = 80%) was 40% (10/25) for the WE method versus 4% (1/25) for the GE method. The GE method has the most clear separation of lipophilic 99Tcm-exametazime from other radiochemical impurities and offers the quickest RCP analysis for 99Tcm-exametazime with relatively accurate results.

[Evaluation of the safety and clinical usefulness of a new myocardial imaging agent, 99mTc-PPN1011--multicenter phase II clinical trial report].

A new myocardial perfusion imaging agent, 99mTc-1,2-bis[bis(2-ethoxyethyl phosphino]ethane (99mTc-PPN1011) was administered to 52 patients with various heart diseases each at rest and peak exercise on different days (Method A) and on the same day (Method B). The safety, optimal dosage, imaging procedures and the clinical usefulness were evaluated. No drug related adverse reactions were found. Image quality was considered adequate for diagnosis with as little as 185 MBq per injection, though the optimal dose range was 370-740 MBq. SPECT images were obtainable as early as 10 min, also until 3 hours after injection. There were no significant differences in clinical efficacy between method A and B, as well as sequential tests at rest and exercise. 99mTc-PPN1011 and 201T1 images in the same patient were compared segment by segment. Image quality of 99mTc-PPN1011 was significantly superior to that of 201T1. Analysis of images indicated that both agent were similar in diagnostic efficacy. It was concluded that 99mTc-PPN1011 is useful for myocardial perfusion imaging.