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Synthesis, characterization, and in vitro evaluation of nitroimidazole--BATO complexes: new technetium compounds designed for imaging hypoxic tissue.

Several technetium-99 BATO (boronic acid adduct of technetium dioximes) complexes TcX(dioxime)3BR (X = Cl) that contain a boron cap R which bears a 2- or 4-nitroimidazole moiety have been prepared from either TcCl(dioxime)3 or from Tc(dioxime)3(mu-OH)SnCl3 [dioxime = dimethyl glyoxime (DMG) or cyclohexanedione dioxime (CDO)]. Two hydroxy analogs (X = OH) were isolated by treatment of the corresponding chloro complexes with aqueous NaOH. The complexes have been characterized by elemental analysis, mass spectrometry, NMR, UV/vis spectroscopy, and high-performance liquid chromatography. These complexes have the potential for selective retention in hypoxic tissue, by a mechanism believed to be the result of nitro reduction. The electrochemistry and enzymatic reduction of these complexes was studied to assess the potential for reduction in vivo. The nitroreductase enzyme xanthine oxidase was shown to reduce the nitroimidazole group on the complexes 99TcOH(DMG)3BBNO2 and 99TcOH(DMG)3BprenNO2 under anaerobic conditions in the presence of hypoxanthine. However, the results indicated that the rate of reduction might be slow in vivo, limiting the suitability of these compounds for imaging of regions of hypoxia.

Anaerobiosis↗

Preparation of no-carrier-added technetium-99m complexes via metal-assisted cleavage from a solid phase.

A novel method for the preparation of no-carrier-added (nca) complexes [99mTc(CO)3L] (L = diethylenetriamine or picolylamine-N-acetic acid) is described. The ligands were covalently bound to a solid support of organic polymers via formation of a tertiary amine from the chelating unit. This C-N bond to the solid phase is selectively cleaved during the formation of the technetium complexes by intramolecular nucleophilic attack of a remaining hydroxy ligand to the alpha-carbon. The complex [99mTc(CO)3L] is released into solution while uncomplexed ligand and uncleaved complex remain solid-phase bound. High specific activity technetium complexes can then be isolated by simple filtration. Cleavage yield depends on temperature, pH, and ligand. Up to 50% release from the solid phase could be achieved under optimized conditions. Corresponding to the 99mTc concentration, free ligand is present in concentrations lower than 10(-7) M. If a targeting vector is conjugated to these ligands, no-carrier-added radiopharmaceuticals can be prepared in that way.

Catalysis↗

Water-soluble phosphines for direct labeling of peptides with technetium and rhenium: insights from electrospray mass spectrometry.

Direct labeling of salmon calcitonin (sCT) is possible in one step using water-soluble phosphines (sulfonated triphenylphosphines) as the reducing agent both for disulfide and for pertechnetate. Phosphines were the most efficient reducing agent for disulfide bonds among those examined. The phosphines both reduced the pertechnetate to Tc(III), and contributed to the technetium coordination sphere in the labeled product. In contrast, the phosphines did not reduce rhenium below oxidation state V, nor did they participate in the rhenium coordination sphere in the labeled peptide. Instead, the expected oxorhenium(V) moiety was incorporated. Both Tc and Re labeling processes gave rise to dimers with two peptides linked by the metal center, as well as simple monomeric species. Positive mode electrospray mass spectrometry not only revealed the presence of phosphine bound to technetium and oxygen bound to rhenium in the metallopeptides but also revealed the oxidation states of the metals. Electrospray mass spectrometry is proving to be an exceptionally valuable technique for characterizing radiopharmaceuticals. Although the one-step direct labeling method described gives mixed products and poor receptor affinity when applied to the small peptide sCT, it might be readily adapted to monoclonal antibodies.

Calcitonin↗

Design, synthesis, and initial evaluation of high-affinity technetium bombesin analogues.

Potent antagonists of bombesin-like peptides have shown great potential for applications in cancer therapy. A 99mTc-labeled agent capable of identifying patients who could benefit from these emerging therapies would have a great impact on patient management. This study involves the synthesis and initial evaluation of technetium diaminedithiolate analogues derived from the potent bombesin analogue Pyr-Gln-Lys-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 (Lys3-bombesin). We coupled two diaminedithiol (DADT) bifunctional chelating agents (BCAs 1 and 2) to the Lys3 residue at the N-terminal region that is not required for binding to the receptor. 99mTc labeling was performed by ligand exchange on addition of [99mTc]glucoheptonate to a solution of the adduct at room temperature. Two products were obtained from each adduct on analysis by HPLC. The major to minor product ratios of the 99mTc-labeled analogues were 3:1 for products from BCA 1 and 9:1 for the products from BCA 2. Macroscopic amounts of the 99Tc analogues were similarly prepared using [99Tc]glucoheptonate. In this case, the major to minor ratios were 2:1 for the products from both BCAs. For initial evaluation of the binding of the Tc-labeled peptides to bombesin receptors, the 99Tc analogues were used in vitro in competitive binding assays in rat brain cortex membranes against [125I-Tyr4]bombesin. Results of the in vitro assays showed that the inhibition constants (Ki) of the major and minor products were 3.5+/-0.7 and 3.9+/-1.5 nM, respectively, for the products from BCA 1; and 7.4+/-2.0 and 5.2+/-1.5 nM for the products derived from BCA 2, respectively. The high affinity exhibited by these technetium analogues is an indication of their potential for use in non-invasive in vivo biochemical characterization of cancers that possess receptors for bombesin.

Amino Acid Sequence↗

Protein and peptide labeling with (cyclopentadienyl)tricarbonyl rhenium and technetium.

A method for labeling proteins and peptides with (methoxycarbonyl cyclopentadienyl)tricarbonyl rhenium and technetium is described. The precursors used for this labeling are conveniently produced from perrhenate and pertechnetate, respectively, using a double ligand transfer reaction. For labeling the lysine residues of the model protein bovine serum albumin, the technetium methyl ester was saponified and then transformed into its N-hydroxysuccinimidyl ester. For the labeling of the model peptides leucine enkephalin, substance P, oxytocin, and the tumor imaging/therapy candidate octreotide, the rhenium methyl ester was saponified and activated using either 1-hydoxybenzotriazole or 1-hydroxy-7-azabenzotriazole. The activation and peptide-coupling reactions were followed using reversed-phase (C18) HPLC and yields averaged approximately 70%.

Chromatography, High Pressure Liquid↗

Comparison of the stability of technetium-labeled peptides to challenge with cysteine.

We have labeled a series of short peptides with technetium-99m either by direct labeling at pH 11 or by exchange from [99mTc]technetium glucoheptonate. Typical labeling yields obtained were as follows: N-acetyl-Gly-Cys(S-Acm)-Gly-Cys(S-Acm)-Gly-NH2 (Acm = acetamidomethyl) 99%, S-benzoyl-mercaptoacetyltriglycine (S-Benzoyl-MAG3) 95%, mercaptoacetyldiglycine-NH2 (MAG2-NH2) 94%, MAG3 92%, N-acetyl-Aib-Aib-Cys-NH2 (Aib = aminoisobutyric acid) 91%, Gly-Gly-Gly-Gly 90%, N-acetyl-Gly-Gly-Cys-Gly 87%, cyclo-1, 4-(Gly-Gly-Gly-Gln) 40%, S-methyl-MAG2-NH2 0%. In the absence of cysteine, all of the labeled peptides were quite stable in solution, with at least 80-90% of the labeled peptide remaining at 24 h. The order of stability of the labeled peptides to challenge with cysteine was found to be MAG3 > S-benzoyl-MAG3 > N-acetyl-Gly-Cys(S-Acm)-Gly-Cys(S-Acm)-Gly-NH2 >N-acetyl-Aib-Aib-Cys-NH2 > MAG2-NH2 > N-acetyl-Gly-Gly-Cys-Gly > cyclo-1,4-(Gly-Gly-Gly-Gln) > Gly-Gly-Gly-Gly. The peptides without a sulfur donor were least stable to challenge with cysteine.

Chelating Agents↗

Syntheses and characterization of dicarbonyl-nitrosyl complexes of technetium(I) and rhenium(I) in aqueous media: spectroscopic, structural, and DFT analyses.

This work describes new synthetic routes to produce mixed carbonyl-nitrosyl complexes of technetium(I) and rhenium(I) in aqueous media. NaNO2, NOHSO4, and NO2(g) have been used to produce in situ nitrous acid as the primary source of NO+. Starting from the organometallic precursor fac-[MX3(CO)3]+, 1 (M = 99Tc, Re; X = Cl, Br), the formation of mixed dicarbonyl-mononitrosyl complexes was observed in aqueous hydrochloric and hydrobromic acid. Time-dependent analyses of the reactions by means of HATR-IR and 99Tc NMR spectroscopy in solution revealed the almost quantitative substitution of one CO ligand by NO+ and, thus, the formation of complexes with facial arrangement of the three pi-acceptor ligands. In the case of technetium, the monomeric complex (NEt4)[TcCl3(CO)2NO] (3a) and the dimeric, chloride-bridged, neutral complex [TcCl(mu-Cl)(CO)2NO]2 (4a) were produced. In the case of rhenium, the monomeric species (NEt4)[ReBr2X(CO)2NO] (X = Br (3b), NO3 (5)) was solely isolated. The X-ray structure of complexes 4a and 5 are discussed. The crystallographic analyses revealed the coordination of the NO+ group trans to the terminal chloride (4a) or the bromide (5), respectively. Crystal data: complex 4a (C4Cl4N2O(6)Tc2), monoclinic, Cc, a = 18.82(3) A, b = 6.103(6) A, c = 12.15(2) A, alpha = 90 degrees , beta = 105.8(2) degrees , gamma = 90 degrees , V = 1343(3) A(3), Z = 4; complex 5 (C10H20N3O(6)Br2Re), orthorhombic, P2(1)2(1)2(1), a = 10.2054(5) A, b = 12.5317(7) A, c = 13.9781(7) A, V = 1787.67(16) A(3), Z = 4. The isolated complexes and their potential facial isomers have been further investigated by density functional theory (DFT) calculations. The energy differences of the isomers are relatively small; however, the calculated energies are consistent with the formation of the observed and isolated compounds. The calculated bond lengths and angles of complex 5 are in good agreement with the data determined by X-ray diffraction. Experiments on the no-carrier-added level starting from fac-[99mTc(H2O)3(CO)3]+ revealed the formation of the complex fac-[99mTcCl(H2O)2(CO)2NO]+ in reasonable good yields. This aqueous-based, synthetic approach will enable the future evaluation of this novel, low-valent metal precursor for potential use in radiopharmacy.

Algorithms↗

Tissue distribution properties of technetium-99m-diamide-dimercaptide complexes and potential use as renal radiopharmaceuticals.

A series of new ligands and the corresponding technetium-99m chelates based on diamide dimercaptide donor groups were synthesized as derivatives of technetium-99m 1,2-bis(2-thioacetamido)ethane, a complex shown to be excreted by renal tubular secretion. Chelation with 99mTc resulted in single radiochemical products or the expected numbers of stereoisomers. They were purified by high-performance liquid chromatography (HPLC) and evaluated in mice as potential renal tubular function agents. The in vivo properties were sensitive to the presence of functional groups, the positional isomerism of the carboxylate group functionality, and the chelate ring stereochemistry of the ligand. The presence of methyl groups slowed renal transit and decreased renal specificity. Cyclohexyl rings fused to the ethylene bridge of the center chelate ring decreased renal excretion while aromatic rings essentially abolished renal excretion. Slow hepatobiliary clearance was observed as an alternate mode of excretion. Polar groups, such as hydroxyl, carboxylate, and carboxamide, increased renal excretion rates and specificity in a stereochemically dependent manner. 99mTc chelates of 1,3-bis(2-thioacetamido)-2-hydroxypropane, 3,4-bis(2-thioacetamido)butanoate and 1,8-dimercapto-2,7-dioxo-3,6-diazanonanoate were identified as promising new renal radiopharmaceuticals.

Amides↗

Thrombus imaging using technetium-99m-labeled high-potency GPIIb/IIIa receptor antagonists. Chemistry and initial biological studies.

Platelet-specific compounds which are radiolabeled with gamma-emitting radionuclides may be particularly useful for the noninvasive in vivo detection of thrombi. The synthesis of peptides which are potent inhibitors of platelet aggregation and which contain a chelator for the radionuclide technetium-99m are described. The target compounds were designed such that stable, oxotechnetium(V) species could be prepared where the site of metal coordination was well defined. A strategy was employed where the pharmacophore-Arg-Gly-Asp-(RGD), or RGD mimetic, was constrained in a ring which was formed by the S-alkylation of a cysteine residue with an N-terminal chloroacetyl group. Binding affinities were enhanced by the replacement of arginine with the arginine mimetics S-(3-aminopropyl)cysteine and 4-amidinophenylalanine. Further enhancements could be obtained by the synthesis of oligomers which contained two or more rings containing receptor binding regions. The increase in binding affinity seen was more than that expected from a simple stoichiometric increase of pharmacophore. The most potent compounds described had IC50s of approximately 0.03 microM for the inhibition of human platelet aggregation. Two of the more potent peptides (P280 and P748) were labeled with technetium-99m and assessed in a canine thrombosis model. The 99m Tc complexes of the peptides prepared in this work hold promise as thrombus imaging agents due to their high receptor binding affinity, ease of preparation, and expected rapid pharmacokinetics.

Amino Acid Sequence↗

Technetium-99m chelators in nuclear medicine. A review.

Nuclear medicine is a branch of medical imaging that uses radioactive tracers to examine the function of body systems. The radionuclide used in about 90% of all examinations is 99Tcm, which is available from 99Mo/99Tcm generators at most nuclear medicine departments. In aqueous medium, technetium is chemically stable as pertechnetate, 99TcmO4-. Injected into the human body, pertechnetate will be absorbed by the thyroid gland because of the similarity to iodide in its radius and charge. To reach targets in the human body other than glandula thyreoidea, 99Tcm needs a carrier molecule, usually a chelating agent. Many chelators that form stable complexes with 99Tcm have affinities for certain tissues in the human body. Other chelators can be manipulated by pharmaceutical formation to be retained in certain body systems. In order to form bonds with technetium, the chelator must contain electron donors like nitrogen, oxygen and sulfur. Space between multiple electron donor atoms is required to allow several bonds to form with the central metal. The stability of the complex increases with increasing number of bonds. Today, chelators for the use with 99Tcm exist for a number of highly sensitive scintigraphic studies of the brain, heart, skeleton, kidneys, hepatobiliary system and lungs. This includes chelators such as dimercaptosuccinic acid, 1,2-ethylenediylbis-L-cysteine diethyl ester, methylenediphosphonate, hexamethylpropyleneamineoxime and hexakis(methoxy isobutyl isonitrile).

Chelating Agents↗

A technetium-99m red cell survival technique for in vivo compatibility testing.

A technique for labeling red cells with Technetium-99m was developed using in vitro reduction by stannous pyrophosphate. The use of Technetium-99m and Chromium-51 enabled simultaneous determination of 60-minute autologous and heterologous red cell survival using small aliquots. In vivo pretransfusion red cell compatibility in a patient with a panagglutinin was identical to that with 51Cr-labeled cells. Simultaneous testing of two heterologous donor units or testing multiple units in the course of a few days was also feasible. In nine studies (one patient and six healthy controls) no significant elution of the 99mTc was observed over 1 hour.

Aged↗

Rapid diagnosis of pedal osteomyelitis in diabetics with a technetium-99m-labeled monoclonal antigranulocyte antibody.

An in vivo method of labeling white cells that diagnoses diabetic pedal osteomyelitis safely, rapidly, and accurately is desirable. The objectives of this investigation were to evaluate a technetium-99m-labeled monoclonal antigranulocyte antibody for diagnosing diabetic pedal osteomyelitis, compared with indium-111-labeled leukocyte and 3-phase bone imaging for this purpose. Twenty-five diabetic patients with pedal ulcers, 22 in the forefoot and 3 in the midfoot, underwent antibody, indium-111-labeled leukocyte, and technetium-99m methylene diphosphonate 3-phase bone imaging. The 1-hour antibody, 24-hour labeled leukocyte, and 3-phase bone images were interpreted separately for the presence of osteomyelitis. The antibody and labeled leukocyte images also were interpreted together with the bone images to determine if the combined study was more accurate than each individual study. There were 10 cases of osteomyelitis among the 25 patients. The sensitivity, specificity, and accuracy of the antibody were.90,.67, and.76, respectively. These results were not significantly different from those obtained with labeled leukocyte imaging:.80,.67, and.72, respectively. The antibody was significantly more specific (P =.004) than 3-phase bone imaging (.27). Interpreting the antibody together with the bone scan did not alter the results. When interpreted with the bone images, the accuracy of labeled leukocyte imaging improved from.72 to.80. This was not significantly more accurate than either the antibody or labeled leukocyte imaging alone. The data suggest that the monoclonal antigranulocyte antibody is comparable with in vitro labeled leukocyte imaging for diagnosing pedal osteomyelitis in diabetic patients, and warrants further investigation in a larger population.

Adult↗

Sentinel node biopsy and lymphoscintigraphy with a technetium 99m labeled blue dye in a rabbit model.

BACKGROUND: Lymphatic mapping for sentinel node biopsy in breast cancer and melanoma usually involves initial peritumoral injection of a radioisotope, gamma camera detection of the sentinel lymph node several hours prior to the operation, and separate perioperative injection of a blue dye. We have developed a combined approach using technetium 99m labeled blue dye (Evans Blue) for use in lymphoscintigraphy that may be injected as a single dose just prior to the operation. METHODS: In an anesthetized rabbit model we dissected a hind limb to display the popliteal node and afferent lymphatic. Technetium 99m Evans Blue ((99m)Tc-EB) (22 MBq; 0.5 mL) was injected subdermally in the dorsum of the paw. Simultaneous digital and gamma camera images were obtained at 14 time intervals to 30 minutes post injection. For each of these time intervals the percentage of radioactivity and percentage blueness of the popliteal node were determined. Urine and afferent lymphatic fluid were analyzed by chromatography. The popliteal node was excised post mortem, placed into solvent solutions and analyzed for blueness and radioactivity. RESULTS: Time-activity curves for radioactivity and time-blueness curves for Evans Blue uptake showed strong correlation (r = 0.958). Lymph analysis suggested (99m)Tc-EB is mainly bound to endogenous proteins. Urine was radioactive but not colored, (99m)Tc-EB being metabolized and excreted in the urine as 1,7-diamino-8-naphthol-2,4-disulfonic acid. Prolonged exposure of node to solvents did not dissociate any blue coloration or radioactivity. CONCLUSIONS: (99m)Tc-EB and Evans Blue are simultaneously retained and concentrated in the sentinel lymph node. This process is rapid and reproducible. (99m)Tc-EB migrates at the same rate as Evans Blue in lymph, where it is transported as bound to endogenous proteins. These dye molecules are metabolized by reductive cleavage in the liver and then excreted renally as colorless, radioactive metabolites. This novel agent has the potential to facilitate lymphatic mapping and subsequent sentinel node biopsy for a range of solid malignancies including breast cancer and melanoma.

Animals↗

Technetium labeled bombesin-like peptide: preliminary report on breast cancer uptake in patients.

Bombesin-like peptides are neurotransmitters and cancer growth factors. Several tumors, breast cancer among them, show one or more than one of the three known bombesin receptors. We have synthesized and labeled with technetium 99m a new pentadecapeptide, analogue to the leu13 amphibian bombesin (99mTc BN). Labeling yield was 83 +/- 4%. Prone Scintimammography was performed on five patients affected by breast cancers (T categorization: two T1b and three T1c), after injecting 0.7 mg, 185 to 296 MBq (5 to 8 mCi) of the peptide. Total body scan did not show free technetium biodistribution. No adverse reaction was observed. Prone Scintimammography with 99mTc Sestamibi (99mTc SM) was also performed few days later. 99mTc BN detected all 5 cancers, whereas 99mTc SM only four: all the T1c and one T1b cancer. Two of them showed axillary node invasion that was detected by both the radiotracers. A fibroadenoma present on contralateral breast to the one with cancer, was not detected neither by 99mTc SM nor by 99mTc BN. Tumor/breast normal tissue ratio (T/B) was constantly higher with 99mTc BN than with 99mTc SM. Maximal T/B was measured as 1.79 with 99mTc SM and 2.25 with 99mTc BN 5 min after fast i.v. administration. In conclusion our 99mTc BN is taken up by primary breast cancer showing higher T/B than 99mTc SM (p < 0.01). In our limited scale, 99mTc BN appears to be safe and, in our limited scale, even more accurate than 99mTc SM for detecting breast cancer.

Aged↗

Technetium-99m methoxy isobutyl isonitrile (MIBI) imaging of the parathyroid glands in patients with renal failure.

BACKGROUND: Technetium-99m methoxy isobutyl isonitrile (Tc-99m MIBI) scintigraphy has been reported to be at least as reliable as thallium-technetium subtraction imaging in the preoperative localization of hyperplastic parathyroid glands in patients with renal failure. Reports have suggested that 50% of glands can be identified correctly by this method. The aim of this study was to improve on previous results and demonstrate that Tc-99m MIBI imaging has an important place in the preoperative work-up of these patients. METHODS: Eighteen patients on renal replacement therapy were studied. All had tertiary hyperparathyroidism and had Tc-99m MIBI imaging prior to parathyroidectomy. A refined reporting method was employed. The imaging results were compared to the subsequent surgical and histological findings. RESULTS: In the 12 patients in whom serum parathyroid hormone levels fell postoperatively to within or below the normal range, 38 of 46 glands (82.6%) were correctly identified and located in the correct quadrant of the thyroid gland. There were two false positive results where the imaging predicted glands not subsequently found by the surgeon. In the patients who had post-operative hyperparathyroidism, repeat Tc-99m MIBI imaging was able to locate accurately the site of the residual parathyroid tissue. CONCLUSIONS: Tc-99m MIBI imaging is able to identify more than 80% of hyperplastic parathyroid glands in renal failure patients if this reporting process is used, and locate them in the correct quadrant of the thyroid gland. Tc-99m MIBI imaging is of particular value when re-exploration of the neck is required for post-parathyroidectomy hyperparathyroidism. These results represent a significant improvement on the sensitivity of this imaging technique when compared to previous published data.

Adult↗

Sacro-iliac joint scanning with technetium-99 diphosphonate.

Quantitative sacro-iliac (SI) joint scanning with methylene diphosphonate labelled with technetium-99 (99TcMDP) was performed in 25 control patients, in 16 patients with definite ankylosing spondylitis, in 23 patients with mechanical low back pain, and in 12 patients with seronegative arthritis. The mean radio-isotope index in the control group was 1.2 +/- 0.15. The highest value was 1.5. Values in excess of 1.5 were seen in patients with clinically active ankylosing spondylitis but not those with inactive disease. Three of the 12 seronegative arthritis patients (without clinical or radiological evidence of sacro-iliitis) had elevated values: all of these were positive for HL-A B27. An important finding was that six of the 23 patients with mechanical or non-specific low back pain had values above 1.5, unassociated with B27. These data emphasize the need for caution in the interpretation of abnormal sacro-iliac scans. Radio-isotope bone scanning can provide a qualitative and quantitative assessment of inflammatory activity in joints with minimal radiation exposure. Various authors have shown its value in providing early evidence of sacro-iliitis (Russell et al., 1975; Namey et al., 1977). In this study, methylene diphosphonate labelled with technetium-99 (99TcMMDP) has been used to produce quantitative sacro-iliac scans in order to evaluate sacro-iliac disease in four groups of patients presenting with or without low back pain.

Arthritis↗

Nuclear scanning with technetium-99m-sestamibi to evaluate ischemia in muscle flaps for cardiomyoplasty.

Mobilization of the latissimus dorsi muscle from the chest wall for cardiomyoplasty interrupts part of its blood supply. The time required for adequate collaterals to develop from the thoracodorsal artery is unknown. In four dogs, the latissimus dorsi muscle was mobilized as for cardiomyoplasty and stimulating electrodes were implanted. The muscle was replaced on the chest wall over a sheet of Gore-Tex (W. L. Gore & Associates, Inc. Flagstaff, AZ) membrane to block growth of collateral vessels from the chest wall. The opposite latissimus dorsi muscle served as the control. After a delay of 2 weeks the latissimus dorsi was burst stimulated at a rate of 80 per min with two 100 msec bursts at 85 Hz and 25 Hz for 30 min. Technetium-99m-sestamibi scans were then done to detect ischemia. Serial studies were done during the next several weeks. Images at 4 weeks demonstrated maximum uptake in the mobilized muscle, which did not subsequently improve. The authors conclude that the mobilized latissimus dorsi muscle can be imaged with technetium-99m-sestamibi and evidence of ischemia resolves at 4 weeks. These findings suggest that collateral flow is adequate as early as 4 weeks after mobilization of the latissimus dorsi muscle for cardiomyoplasty.

Animals↗

Technetium generator log form.

Technetium generators are loaded with molybdenum-99 (99Mo), that has a 66-h half life and decays to technetium-99 m (9mTc). 99Tc with a single 140 keV gamma photon emission and a 6-h half life is an ideal isotope for nuclear medicine imaging. Many nuclear medicine units receive generators and use the 99Tc elution to label a variety of prepared chemical species for the majority of the studies they perform. Other options are receiving bulk 99mTc and doing the same tagging or getting unit doses of already labeled pharmaceuticals. Units using generators must meet requirements spelled out in regulations of the Nuclear Regulatory Commission, Title 10, CFR, parts 20, 35, and 71 as well as the Department of Transportation, Title 49, CFR, part 173. The form described in this paper was an attempt to get all of the required records for each individual generator on a single sheet of paper.

Forms and Records Control↗