Variable threshold levels for estimation of renal uptake of 99mTc-dimercaptosuccinic acid based on single photon emission computed tomography

To calculate renal uptake of 99mTc-dimercaptosuccinic acid (DMSA) more accurately using single photon emission computed tomography (SPECT), it is necessary to estimate values of threshold level, which corresponds to the ratio of kidney to background (BG ratio). Thus the phantom and clinical studies were conducted. Six kinds of renal phantoms of 80 to 339 ml, contained different radioactivity of 37 to 485 MBq were prepared. These phantoms were placed in a larger body phantom filled with 1 to 50% of radioactivity representing background. Clinical application of this method was also performed. Results were as follows. 1) A significant correlation between phantom volumes and estimated volumes obtained using threshold level based on BG ratio calculated on tomographic images was found (r = 0.99). 2) A significant correlation between total counts in estimated volumes and radioactivities in phantoms was recognized (r = 0.94). 3) Known radioactivity in phantoms and radioactivity in estimated volumes were highly related (r = 0.98). 4) Clinical application showed valuable results in patients with renal dysfunction. Thus, this method can calculate more accurate renal uptake of 99mTc-DMSA.     

Study on tumor affinity of technetium-99m-labeled radiopharmaceuticals. (2) 99mTc-Sn-diphosphonate (99mTc-EHDP), 99mTc-Sn-dimercaptosuccinic acid (99mTc-DMSA), and 99mTc-Sn-diethyl stilbestrol diphosphate (99mTc-DSDP)]

The authors have examined the tumor affinity of various 99mTc-labelled radiopharmaceuticals to Ehrlich's tumor for the purpose of delineating positively human malignant neoplasm. This paper includes biologic distributions of 99mTc-Sn-diphosphonate (99mTc-EHDP), 99mTc-Sn-dimercaptosuccinic acid (99mTc-DMSA) and 99mTc-Sn-diethyl stilbestrol diphosphate (99mTc-DSDP, 99mTc-Honvan) as the second report on the tumor affinity to the Ehrlich-bearing mice. (a) Tumor concentration of 99mTc-EHDP was lowest and the positive delineation of implanted tumor with 99mTc-EHDP was poorest in sequential images, though the active accumulation to some soft tissue maglinant neoplasms, the breast cancer and the thyroid cancer, has been reported. (b) Tumor concentration and tumor to blood ratio of 99mTc-DMSA were not so high on the contrary of our expectation that 197Hg-DMSA may show the high tumor concentration and the high tumor to blood ratio like 197Hg chlormerodrin as same renal scanning radiopharmaceuticals. (c) Tumor concentration of 99mTc-DSDP was highest. Tumor to blood concentration ratio, however, was lower than that of the above mentioned radiopharmaceuticals but tumor to liver ratio and/or tumor to lung ratio was over 1.0 at the earlier time. Biologic distribution of 99mTc-DSDP was similar to that of 32P labeled DSDP and then it is presumed that 99mTc is labeled at phosphate ester of DSDP which is dephospholytated immediately by phospholylase in vivo following the intravenous injection. Therefore, it may be assumed that the accumulation mechanism of 99mTc-DSDP to Ehrlich's tumor is related to the phospholylase activity in neoplasms but is not known precisely.     

Estimation of 99mTc-dimercaptosuccinic acid renal uptake using single photon emission computed tomography

Renal function was assessed by measurement of 99mTc-dimercaptosuccinic acid (DMSA) uptake by the kidney based on the transsectional tomographic image obtained by single photon emission computed tomography (SPECT). The renal uptake was expressed as percentage of the total radioactivity detected in the kidney, the volume of which was measured by convolution method, against the amount dosed. Absorption was corrected by GE-STAR method using cut off level of 42%. In order to determine normal range, measurement was made for 40 kidneys of each of 10 male and female volunteers confirmed of having normal kidneys both morphologically and functionally. The average volume of the kidney was 220.4 ml for the right and 239.3 ml for the left for males, and 205.9 ml and 236.5 ml, respectively for females. The renal uptake of radioactivity (at 2 h after injection), was 26.8% for the right and 27.6% for the left for males, with corresponding figures for females being 26.4% and 27.9%, respectively. Distribution range of renal volume and renal uptake was obtained by bivariate analysis with 90% and 95% probability. From these results, our method of renal function determination based on renal uptake of 99mTc-DMSA obtained from renal transactional tomogram by SPECT is considered to be accurate and potentially useful for clinical purpose.     

Studies of intrarenal distribution by macroautoradiogram and tissue distribution of 99mTc-gluconate (author's transl)]

1) The experimental studies have demonstrated that 99mTc-gluconate reaches a high concentration in the kidneys within 1-2 hours after injection and its concentration in organs adjacent to the kidney is low. 2) The initial images of serial macroautoradiograms visualized the inner medulla as well as the cortex and outex medulla, whereas the delayed images revealed only the outer cortex and outer stripes in the outer medulla. These findings suggest that this renal agent consists of two components and the delayed component deposits in the convoluted and straight segments of proximal tuble. 3) This renal agent visualizes the calyceal system and excretory pathways in the initial study and the renal morphology in the delayed study. Therefore, using this renal agent, it may be possible to evaluate a variety of renal diseases, including obstructive uropathy, space-occupying lesions, congenital deformities, etc,.     

Synthesis of (S)-N-[methyl-11C]nicotine and its regional distribution in the mouse brain: a potential tracer for visualization of brain nicotinic receptors by positron emission tomography.

A nicotine agonist, 11C-labeled (S)-nicotine, was synthesized by N-methylation of (S)-nornicotine with [11C]-methyl iodide in dimethylformamide-dimethylsulfoxide in order to study nicotinic receptors in the human brain by positron emission tomography. The radiochemical yield of this N-methylation reaction was more than 90% within 5 min. After purification by high performance liquid chromatography the radiochemical purity of the product was more than 99% and the specific radioactivity was 7.4-11.1 GBq/mumol. The regional distribution of (S)-[11C]nicotine in the mouse brain after intravenous injection was compared with that of (R)-[11C]nicotine. After injection of (S)-[11C]nicotine, the regional uptake of radioactivity was in the following order: cortex greater than thalamu approximately hippocampus greater than striatum greater than hypothalamus greater than cerebellum. Moreover, (S)-[11C]nicotine was displaced from the brain by unlabeled (S)-nicotine, but unlabeled (R)-nicotine caused no change in uptake. In contrast, (R)-[11C]nicotine showed a lower brain uptake and lesser regional differences in radioactivity.     

Determination of radiochemical purity of chlormerodrin-203 by electrophoretic method

An electrophoretic method to control the radiochemical purity of chlormerodrin-203 is described. Optimum conditions for the separation of inorganic and organically bound mercury-203 were determined by investigating its mobility in the concentration range of 1·10⁻⁵–1·10⁻² M NaCl. Maximum separation, of²⁰³Hg and hydroxychlormerodrin was achieved at 0.05M NaCl, at the potential gradient of 8V/cm for 2 hrs.     

高分子色谱固定相GDX203的改性及其在色谱分离中的应用

通过对高分子色谱固定相GDX 2 0 3的硝化改性处理 ,得到新型色谱固定相改性GDX 2 0 3.该固定相用于甲醇羰基合成醋酸的反应产物分析 ,可在恒温条件下快速分离反应介质中的全部组分 ,尤其是乙酸甲酯和碘甲烷可得到完全分离     

Evaluation of 3H-paroxetine as a radioligand for in vivo study of 5-hydroxytryptamine uptake sites in mouse brain

The distribution of radioactivity in the mouse brain after intravenous administration of 3H-paroxetine was in the order (highest to lowest) hypothalamus greater than cerebral cortex greater than cerebellum. The radioactivity in the hypothalamus and cerebral cortex after injection of 3H-paroxetine was significantly decreased by treatment with 6-nitroquipazine or paroxetine. HPLC and TLC analyses show that no radioactive metabolites were found in the mouse brain 3 h after intravenous administration of 3H-paroxetine. The present results indicate that 3H-paroxetine would be a suitable radioligand for in vivo study of 5-HT uptake sites in mouse brain.     

Attenuation correction of SPECT imaging by dual energy method--quantification of 111In-labeled monoclonal anti-tumor antibody localization

Application of radiolabeled monoclonal anti-tumor antibodies for diagnosis and therapy has made remarkable progress in the past few years. Quantification of radiopharmaceutical localization is required adequate attenuation correction in SPECT imaging. Attenuation correction by transmission CT (TCT) data is one of the best method at present time. However, if a patient is moved between TCT and SPECT, this method is no more applicable. We developed a new attenuation correction algorithm by dual energy method, using 99mTc and 111In because of similarity of these linear attenuation coefficients. The new algorithm uses data of TCT with an external source of 99mTc, and requires another data from SPECT of 111In labeled monoclonal anti-tumor antibody, which are simultaneously obtained. TCT results in an attenuation map, which then serves as input into the final intrinsic correction algorithm to uncorrected SPECT data. In chest phantom experiment, the attenuation corrected SPECT images revealed nearly same distribution of actual radioactivity of 111In as compared to that of uncorrected one.     

Determination of airborne mercury-203

A method is described for the determination of airborne compounds of²⁰³Hg. The method is based on the sorption of Hg on hopcalite (activated copper oxide/manganese oxide) with subsequent monitoring for the gamma-radiation of²⁰³Hg. Aerosol activity in the air is separated by sucking the air through a filter prior to the absorption tube. The sensitivity of the method permits the assessment of less than one tenth of the maximum permissible concentration in air. It is shown experimentally that the separation procedure used is suitable for the determination of airborne mercuric acetate and its thermal decomposition products.     

An efficient total synthesis of a sphingosine-1-phosphate receptor agonist KRP-203

An efficient total synthesis of the S1P₁ agonist, KRP-203, is described. The key step involves the conjugate addition of diethyl acetamidomalonate to a styrene compound to give the core structure of KRP-203. Multigram quantities of the targeted KRP-203, sufficient for several biological studies, were obtained in six steps with an overall yield of 58%.     

An efficient method for preparing the sphingosine-1-phosphate receptor agonist, KRP203-phosphate

An efficient method for mono-phosphorylation of 2(KRP203)using cbz-protection,dibenzylphosphoryl chloride and TMSI affording 2-P(KRP203-P)was developed.We applied the present method to the synthesis of KRP203 phosphate analogs which were difficult to produce through tradition procedures.     

Comparative studies on 99mTc-pyrophosphate and 85Sr-chloride for skeletal imaging

In order to know the potential merits of 99mTc-pyrophosphate (99mTc-PYP) skeletal imaging, a comparative study was carried out by administering to the rabbit 85Sr-chloride (85Sr), classical bone-seeking agent, and 99mTc-PY simultaneously. Radioisotopic distribution was investigated as regards their deposition in the pelvic bones, and sharpness of the skeletal scintigrams, too. Both agents were remarkably affinitive to the skeletal system and there were remarkably differences in their temporal deposition pattern. Marked deposition was observed of either agent in the metaphyses. With 99mTc-PYP, the vertebral and costal systems were delineated symmetrically and each vertebral body was distinctly depicted as such 99mTc-PYP many possess the following merits over 85Sr; (1) owing to its physical properties, sufficiently large radioactivity of 99mTc-can be administered; (2) body burden of radiation absorption is reduced; (3) skeletal scintigrams of high quality are obtainable in a short period of time.     

Separation of (203)Pb by ion-exchange chromatography on chelex 100 after production of (203)Pb by the Pb(p, xn)(203)Bi--> EC.beta+ (203)Pb nuclear reaction

Bismuth radioisotopes, produced by 50-MeV proton bombardment of a lead target in a cyclotron, are separated from the lead target material by ion-exchange chromatography on a column containing 5.0 ml of Chelex 100. After a decay period of 24 hr, the (203)Pb formed in situ is eluted from the column and then separated from (200)Tl and (201)Tl on a second ion-exchange column containing 0.5 ml of Chelex 100. Separations are sharp and carrier-free (203)Pb is obtained.     

Evaluation of 99mTc-HIDA complex as a cholescintigraphic agent (author's transl)

In the reaction labeling N-(2,6-dimethylphenylcarbamoylmethyl) iminodiacetic acid (HIDA) with 99mTc, several complexes with different chemical characteristics were observed to occur with slight changes in the labeling conditions. Among these complexes, a complex detected in the bile of rats was limited to one complex, named as complex II. The preparation method of 99mTc-HIDA complex II and the exchange reaction between this complex and penicillamine indicate that 99mTc is coordinated with HIDA as low-hydrolyzed 99mTc in this complex. This complex is excreted rapidly through the bile and within 1 hr, about 65% of the total activity injected is recovered from bile in rats. The organ distribution of this complex was studied in mice by radioassay and in rabbits by scintillation camera and, in both cases, the radioactivity was accumulated in the gallbladder. These results suggest that the 99mTc chemical state, low-hydrolyzed state, relates to the bile excretion behavior of this complex, a potentially useful cholescintigraphic agent.     

Phosphonate complexes of 99mTc - Potential bone scintigraphy agents

The synthesis of several combined aminophosphonate ligands containing an N-carboxymethyl group is described. The complexes of these ligands were prepared both with ^99mTc and ⁹⁹Tc, and the dependence of their formation on pH and the stoichiometry of reagents was studied. All of the complexes were pharmacologically evaluated. The distribution of radioactivity and bone uptake were determined, and discussed in comparison with clinically used phosphonate complexes. This revised version was published online in August 2006 with corrections to the Cover Date.     

Radioactive metal complexes with affinity for tumors. II. Biodistribution of radioactivity in cellular and subcellular fractions of tumor tissues

The 99mTc and 57Co complexes of ethylenediamine-N,N-diacetic acid (EDDA) are accumulated in tumor tissue. The complexes and related radioactive compounds were administered to experimental animals bearing Ehrlich tumor, and the blood, tumor, abscess, and other tissues were separated, fractionated and analyzed. In blood, the EDDA complexes of 99mTc and 57Co were in dialyzable forms, whereas other tumor-nonlocalizing compounds were in undialyzable or protein-bound forms. The tumor/blood and tumor/muscle ratios of the radioactivity showed that the complexes had the high affinity for tumor tissues. Density gradient centrifugation analysis of the ascites tumor tissues showed that a significant amount of the radioactivity of the complexes was present in tumor cells. Subcellular fractionation of solid tumor tissue showed that the radioactivity was present in nuclear fraction.     

Radioactivity distribution measurement of various natural material surfaces with Imaging Plate

Distribution images of natural radioactivity in natural materials such as vegetables were obtained by using Imaging Plate. In such cases, it is necessary to reduce background radiation intensity by one order or more. Graded shielding is very important. Especially, the innermost surface of a shielding box should be covered with acrylic resin plate. We obtained natural radioactivity distribution images of vegetables, sea food, meat etc. Mostly -rays emitted from⁴⁰K print the radioactivity distribution image. Comparison between -ray intensity of KCl solution measured with HPGe detector and that of natural material specimen gave the radioactivity around 0.060.4 Bq/g depending on the kind and the part of specimens.     

Differential determination of203Hg and14C or35S in double labelled biological samples

The differential determination of²⁰³Hg and¹⁴C or³⁵S in double labelled biological samples is presented. The biological samples were mineralized with 70% HClO₄ and 30% H₂O₂ in minivals MILLI-6. The γ-activity of²⁰³Hg was measured on a well scintillation counter. The total activity, due to²⁰³Hg and¹⁴C or³⁵S, was measured by the liquid scintillation technique after addition of Aquasol into the same vials. The method of external standard channel ratio was used for standardization. Very good recoveries were obtained: 100±0.7% for²⁰³Hg and 94.6–101.0% for¹⁴C and³⁵S. This method could be used for other β, γ and β-active nuclides with similar β-spectra.     

Technetium-99m complexes with steroid-2-aminooxyethyliminodiacetic acid conjugates

Conjugates of 2-aminooxyethyliminodiacetic acid with estrone, testosterone, epiandrosterone, 17-alpha-hydroxy-progesterone and progesterone were synthesized and their complexes with Tc-99m were successfully prepared in good yields, which indicated the agent to be promising for metal-labeling of biomolecules and related substances containing one or more carbonyl groups. The biodistribution and scintigraphic studies in mice bearing Ehrlich tumor and mammary tumor showed that the radioactivity accumulated considerably in the tumor tissues, but the tumor images were somewhat obscured.