99mTc-human immunoglobulin (HIG) — first results of a new agent for the localization of infection and inflammation

Technetium (^99mTc) labelled, polyclonal human immunoglobulin (HIG) is a new agent that detects focal infection and inflammation. This new agent was compared in 40 patients with the accepted standard, namely¹¹¹In-oxine-labelled leucocytes. This comparison resulted in a sensitivity of 94% and a specificity of 96% for^99mTc-HIG when¹¹¹In-oxine leucocytes were defined as giving the true result. The new agent was shown to localize both sepsis and active inflammatory bowel disease (IBD). There was 100% concordance in the 16 patients with IBD who were imaged with both^99mTc-HIG and¹¹¹In-oxine leucocytes. Discordant results were obtained in one case of suspected osteomyelitis, which was false-positive on the^99mTc-HIG scan, and one case of pyrexia of unkown origin when the^99mTc-HIG was false-negative and the¹¹¹In-oxine leucocyte scan demonstrated accumulation of tracer in the caecum at 24 h post-injection. Normal distribution for^99mTc-HIG demonstrated activity in the kidneys and bladder and that 50% of the tracer is cleared through the kidneys during the first 24 h post-injection. There were no major or minor side-effects.     

Tc-99m dextran: a new and sensitive general purpose scintigraphic agent for diagnosing intestinal inflammation.

PURPOSE: This feasibility study was undertaken to compare the sensitivity of Tc-99m dextran with that of Tc-99m human immunoglobulin G to diagnose ulcerative colitis, and to explore its possible role in disease follow-up. MATERIALS AND METHODS: Twenty-six patients with active disease and six patients in remission underwent serial Tc-99m dextran scanning for as long as 3 hours or more after injection. Eight of the patients with active disease also underwent Tc-99m human immunoglobulin G imaging. RESULTS: Twenty-four of 26 (92%) patients with active ulcerative colitis had a positive result of the Tc-99m dextran study, mainly within 1 hour. In comparison, Tc-99m human immunoglobulin G accumulated abnormally in four of eight (50%) patients and had a relatively poor target localization with high persisting background even after 6 hours. Four of the six patients in remission still had a positive result of the dextran scan, but the abnormal uptake was less than that in the patients with active disease. The disease has recurred already in one of these patients. A patient with pancolitis who was receiving steroid enema therapy had intense uptake of Tc-99m dextran in the ascending colon, probability because it was outside the range of the enema. CONCLUSIONS: Tc-99m dextran is a sensitive and cost-effective agent to diagnose ulcerative colitis, and it may have a role in disease follow-up.     

99mTc-diethyl-iodo-HIDA (JODIDA): a new hepatobiliary agent in clinical comparison with 99mTc-diisopropyl-HIDA (DISIDA) in jaundiced patients

The new HIDA derivative, 99mTc-diethyl-iodine-HIDA (JODIDA), was compared with 99mTc-diisopropyl-HIDA (DISIDA) in 17 patients with jaundice by means of paired cholescintigraphic imaging studies. The following parameters were visually assessed: the extent of urinary tract visualization, biliary contrast and appearance time, and gallbladder visualization and appearance time. In the 6 patients with a total bilirubin level of between 19 and 66 mumol/l (1.1 and 3.9 mg/dl), both radiopharmaceuticals gave similar results except for the moderate visualization of the urinary tract with DISIDA in contrast to JODIDA. In the remaining 11 patients with a total bilirubin level between 102 and 1303 mumol/l (6 and 76 mg/dl). JODIDA showed significant advantages over DISIDA: nonvisualization of the urinary tract, stronger and faster biliary contrast, and better gallbladder visualization. JODIDA thus offered substantial diagnostic advantages over DISIDA in 8 of these patients. In 4 patients, the differential diagnosis of jaundice (intrahepatic or mechanical disorder) was possible with JODIDA, whereas DISIDA either could not visualize intestinal or gallbladder activity at all or could not differentiate it from the urinary tract. In one patient, JODIDA offered faster (18 h) diagnosis. In the remaining 3 patients, other, substantially false interpretations could be avoided through the use of JODIDA. Further clinical experience with JODIDA in more than 40 patients confirmed the results of this study. We concluded that JODIDA is of significant advantage over DISIDA in clinical situations such as total bilirubin level above 80-100 mumol/l (4.7 to 5.8 mg/dl), examination of small children and critically ill patients and suggestion of bile leakage.(ABSTRACT TRUNCATED AT 250 WORDS)     

99mTc-MAG3, a new renal imaging agent: Preliminary results in patients

^99mTc-mercaptoacetyltriglycine (MAG₃) is a new renal radiopharmaceutical which has been shown to have biological properties similar to¹³¹I-hippurate (OIH) in animals and volunteers.^99mTc-MAG₃ has now been compared with¹³¹I-orthoiodohippurate (OIH) in a group of patients with varying degrees of renal impairment. In all cases, the^99mTc-MAG₃ images were superior regardless of serum creatinine. Selected examples are illustrated including scans and renogram curves in a normal volunteer, transplant patients with creatinines of 9.8 mg/dl and 2.6 mg/dl respectively, and a furosemide study in a patient with questionable obstruction. Our preliminary results suggest that^99mTc-MAG₃ performs well in patients with impaired renal function and may well provide an acceptable replacement for OIH. A kit formulation has been developed and will soon be undergoing clinical evaluation.     

Evaluation of 99mTc-RP128 as a potential inflammation imaging agent: human dosimetry and first clinical results.

99mTc-RP128 is a bifunctional peptide chelate designed to target the tuftsin receptor, expressed by neutrophils, monocytes, and macrophages. Studies in animal models of both infectious and noninfectious inflammation have shown a positive correlation between accumulation of 99mTc-RP128 and quantitative measures of inflammation. A phase 1 trial was conducted with the objective of determining the safety, biodistribution, and human dosimetry of 99mTc-RP128 in eight healthy volunteers. For evaluation of the potential of 99mTc-RP128 for imaging sites of inflammation, 10 patients with active rheumatoid arthritis were studied. METHODS: Normal biodistribution was determined using the conjugate view method up to 24 h after intravenous injection of 280 MBq 99mTc-RP128. Dosimetry calculations were based on standard MIRD methodology, using the International Commission on Radiological Protection model 30 of the gastrointestinal tract and a voiding bladder model with an interval of 4.8 h. For rheumatoid arthritis patients, whole-body scans and spot views of the hands, knees, and feet were obtained at 1 and 3 h after injection of 475 MBq 99mTc-RP128. RESULTS: 99mTc-RP128 was cleared rapidly from the blood by renal excretion, and no major organs showed significant accumulation. The synovia of the major joints were visualized for all subjects. The effective dose equivalent and the effective dose were calculated to be 0.011 and 0.0094 mSv/MBq, respectively. The highest dose was to the bladder wall, which received 0.076 mGy/MBq. In all rheumatoid arthritis patients, we observed a markedly increased uptake in several affected joints. Painful and swollen joints were detected with a sensitivity of 76% and 69%, respectively. Seventy-three percent of the joints with radiographic signs of erosion were scintigraphically positive. In some patients, lines of increased activity were observed and were considered to correspond to uptake in the synovium lining tendon sheaths in the wrists and hands. CONCLUSION: This study shows that 99mTc-RP128 is safe and can successfully be used to visualize clinically affected joints in patients with long-standing rheumatoid arthritis. A proposed radioactive dose of 450-500 MBq will produce an effective dose well within the range of effective doses for commonly used radiopharmaceuticals.     

心肌显像剂[99Tcm(CO)3(MIBI)3]+和99Tcm-MIBI药理实验对比研究

目的对心肌显像剂羰基99Tcm-甲氧基异丁基异腈(MIBI)([99Tcm(CO)3(MIBI)3]+)和99Tcm-MIBI进行动物药理对比研究.方法制备[99Tcm(CO)3(MIBI)3]+注射液,放化纯85%.实验犬3只,每次静脉注射剂量555 MBq,通过动态采集、全身显像和采集血样,获得药代动力学参数、体内生物分布、靶/非靶比值和药效学结果.结果 [99Tcm(CO)3(MIBI)3]+符合一次静脉给药的药代动力学二室模型,快相清除半衰期T(α)1/2=(1.33±0.12) min,慢相清除半衰期T(β)1/2=(102.33±25.58) min,总清除速率(CL)=(401.33±73.51) mL/h.心、肝、肺时间-放射性曲线显示[99Tcm(CO)3(MIBI)3]+肝摄取曲线幅度低于心肌曲线,而99Tcm-MIBI肝曲线明显高于心肌曲线.10、30、60、90和120 min[99Tcm-(CO)3(MIBI)3]+在心、肺、肝百分注射剂量(%ID)与99Tcm-MIBI比较,前者心肌摄取较高,肺本底较低,肝摄取低.[99Tcm(CO)3(MIBI)3]+心/肺和心/肝比值均高于99Tcm-MIBI,差异有显著性,P均<0.01.静脉注射[99Tcm(CO)3(MIBI)3]+后10～120 min均可获得清晰的心肌图像,肝胆排泄较快,肝内放射性较低,左室下壁不受肝影影响,无需脂餐促进肝胆排泄.结论 [99Tcm(CO)3(MIBI)3]+有望成为一种新的心肌灌注显像剂.     

Technetium-99m (99mTc) mercaptoacetyltriglycine: update on the new 99mTc renal tubular function agent.

Technetium-99m (99mTc) mercaptoacetyltriglycine (MAG3) is a new renal radiopharmaceutical that was recently introduced as a 99mTc-labeled replacement for iodine-131 (131I) o-iodohippurate (OIH). Since its introduction, a wide variety of in vitro and in vivo studies have been performed to characterize the high-performance liquid chromatography (HPLC)-purified complex and kit formulations. [99mTc]MAG3 has a slower plasma clearance, a higher plasma protein binding, less red blood cell (RBC) penetration, a lower extraction ratio, and a smaller volume of distribution than OIH. Because of the slower plasma clearance, [99mTc] MAG3 cannot be used as a direct measurement of effective renal plasma flow. Simplified methods have been developed to calculate [99mTc]MAG3 clearances, as well as regression equations to convert these clearances to an equivalent OIH value. The image quality of [99mTc]MAG3 is superior to [131I]OIH; the renogram curves and the fraction of the dose of the two agents that appears in the urine are almost identical, even though the plasma clearance of [99mTc]MAG3 is only 50% to 65% that of OIH. [99mTc]MAG3 compares favorably with OIH in patients with a wide range of clinical problems. The radiation dose to a patient with normal renal function using standard imaging doses is higher for [99mTc]MAG3 than for [131I]OIH, but in patients with impaired renal function, the radiation dose from [131I]OIH is much higher than [99mTc]MAG3. [99mTc]MAG3 also provides superior image quality compared with [99mTc]diethylenetriaminepentaacetic acid (DTPA) in patients with impaired renal function, but it is important to note that [99mTc]MAG3 cannot be used to measure the glomerular filtration rate (GFR). [99mTc]MAG3 is the most promising 99mTc tubular function agent to date, and it has replaced OIH and [99mTc]DPTA in a number of institutions. However, there are physiologic differences between these three agents and, therefore, they should not be expected to behave identically in all clinical conditions.     

Synthesis and evaluation of a new bifunctional chelating agent for 99mTc labeling proteins: p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone)

A new bifunctional chelating agent, p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), containing a di(N-methylthiosemicarbazone) as the technetium coordinating site and an aralkyl carboxylate site for the protein conjugation was synthesized. Coupling to human serum albumin (HSA), selected as a model protein was carried out by the phosphorylazide method using diphenylphosphoryl azide (DPPA). The conjugation level of CE-DTS to HSA played a critical role in its biological evaluation. A 99mTc-CE-DTS-HSA with high in vivo stability was obtained when CE-DTS was coupled to HSA at 1:1 molar ratio. This compound showed similar in vivo stability to 131I labeled HSA in mice and rabbits.     

99mTc-depreotide in the evaluation of bone infection and inflammation

BACKGROUND AND AIM: (99m)Tc-depreotide is a (99m)Tc-labelled somatostatin analogue, with high affinity for the 2, 3 and 5 subtypes of somatostatin receptors. These particular receptors are over-expressed on the surface of activated leucocytes, which mediate inflammatory response. Based on this property this study tried to investigate whether (99m)Tc-depreotide scintigraphy could be a useful complementary method in the investigation of bone infection and inflammation. METHODS: Twenty-three patients, who were investigated for probable osteomyelitis, underwent three-phase bone scintigraphy followed by (99m)Tc-depreotide scintigraphy. Clinical and laboratory findings, complementary imaging procedures, clinical follow-up and bone biopsy established the final diagnosis. (99m)Tc-depreotide scintigraphy was performed 3 h after the intravenous administration of 555-740 MBq of the radiopharmaceutical. Scintigraphic images were, at first, blindly interpreted alone and then in comparative assessment with bone scans. RESULTS: (99m)Tc-depreotide was positive in 12/12 cases of active osteomyelitis, one case of recent femoral head osteonecrosis and 6/9 rheumatoid arthritis sites. Negative (99m)Tc-depreotide scans were acquired in five cases of 'no-inflammation' (an uncomplicated fracture, an aseptic loosening of prosthesis, an old osteonecrosis, a healed and a successfully treated osteomyelitis), as well as in 14/14 total sites of degenerative arthritis-osteoarthropathy. In five cases (septic arthritis, periodontal and soft tissue infections) (99m)Tc-depreotide was positive, though spatially discordant with bone scintigraphy, delineating precisely the focus of infection. CONCLUSION: (99m)Tc-depreotide can be a useful complementary imaging method in the evaluation of bone infection and inflammation. Its combination with three-phase bone scintigraphy seems to be accurate in localizing the infection foci and determining the activity of the inflammatory processes.     

前哨淋巴结显像剂99Tcm-IT-Rituximab的制备及其定位性能

目的研究前哨淋巴结（SLN）显像剂^99Tc^m-亚氨基噻吩（IT）．美罗华（Rituximab）的标记方法及其定位效应。方法采用2-IT作为双功能连接剂，制备^99Tc^m-IT-Rituximab，确定最佳反应条件，评价标记抗体分子完整性及生物活性。观察比较^99Tc^m-IT-Rituximab及^99Tc^m-硫胶体（SC）2种示踪剂在小鼠淋巴结中的定位性能。将^99Tc^m—IT—Rituximab作为显像剂，对10例乳腺癌患者行乳腺癌SLN动态显像。结果2-IT与Rituximab连接的最佳物质的量比为10：1，4℃反应45min后，每分子抗体螯合上的游离巯基数平均为2．1个。IT—Rituximab分子保持完整、免疫活性保留完全。^99Tc^m-IT-Rituximab的标记率〉90％，其与B淋巴瘤细胞株Raji细胞的结合率为69．4％。动物显像结果显示^99Tc^m—IT—Rituximab可清晰定位小鼠SLN，注射后30min～24h SLN均可显影，2h后SLN显影清晰，至24h未见次级淋巴结显影。动物体内分布数据显示^99Tc^m-IT-Rituximab定位性能明显优于^99Tc^m-SC，24h时SLN百分注射剂量率（％ID）为4．49％，次级及第3级淋巴结基本无摄取，24h注射点滞留率为22．14％。结论该标记方法简单，标记率高；^99Tc^m—IT—Rituximab在SLN中定位性能良好，是一种潜在的新型SLN显像剂。     

新型心肌灌注显像剂~(99)Tc~mN-MIBI的药盒研制及质量控制

目的　建立心肌灌注显像剂99TcmN 甲氧基异丁基异腈 (MIBI)的药盒法制备及其质量控制方法。方法　由条件实验确定药盒中各组分的最佳含量。参照《中国药典》(1995年版 )方法进行澄清度、pH值、无菌以及急性毒性检查。将药盒置于不同环境下存放不同时间 ,通过外观、主药含量及配合物标记率的变化来检查药盒的稳定性。结果　药盒的澄清度、pH值、无菌以及急性毒性检查合格 ,稳定性好。药盒法制备的配合物标记率大于 95 %。结论　药盒法制备99TcmN MIBI配合物简便易行 ,符合临床试用要求。     

Biodistribution and dosimetry of 99mTc-ciprofloxacin, a promising agent for the diagnosis of bacterial infection

This study reports on the biodistribution and dosimetry of technetium-99m ciprofloxacin, a radio-ligand developed for the visualisation of bacterial infection. Whole body scans were performed up to 24 h after intravenous injection of 370 MBq 99mTc-ciprofloxacin in three male and three female volunteers. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole body clearance. Time-activity curves were generated for the thyroid, heart, liver and whole body by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. The images showed rapid, predominantly urinary excretion of 99mTc ciprofloxacin, with low to absent brain, lung and bone marrow uptake and low liver uptake and excretion. Accordingly, imaging conditions are excellent for both the thoracic and the abdominal region, even at early time points (60 min) post injection. In none of the volunteers was the gallbladder visualised. Approximately 60% of the injected activity was recovered in urine by 24 h post injection. The highest absorbed doses were received by the urinary bladder wall, the thyroid, the upper large intestine, the lower large intestine and the uterus. The estimated mean effective dose for the adult subject, taking into account the weight factors of the ICRP60 publication, was 0.0083 mSv/MBq. The amount of 99mTc ciprofloxacin required for adequate planar and tomographic imaging results in an acceptable effective dose to the patient.     

~(99)Tc~m标记双膦酸盐骨显像剂的研究进展

双膦酸盐是一类具有很强亲骨性的药物,99Tcm标记的双膦酸盐如~(99)Tc~m-亚甲基二膦酸盐(~(99)Tc~m-MDP)等被广泛应用于骨显像.近些年来,为了克服~(99)Tc~m-MDP的缺点,许多新型的双膦酸配体被设计与合成,以期望获得性能更加优异的骨显像剂.该文对近10年来发展的99Tcm标记双膦酸盐类骨显像剂的结构与性能进行了综述.     

99mTc-Diethyl-iodo-HIDA (JODIDA): A new hepatobiliary agent in clinical comparison with 99mTc-diisopropyl-HIDA (DISIDA) in jaundiced patients

The new HIDA derivative, ^99mTc-dimethyl-iodine-HIDA (JODIDA), was compared with ^99mTc-diisopropyl-HIDA (DISIDA) in 17 patients with jaundice by means of paired cholescintigraphic imaging studies. The following parameters were visually assessed: the extent of urinary tract visualization, biliary contrast and appearance time, and gallbladder visualization and appearance time. In the 6 patients with a total bilirubin level of between 19 and 66 mol/l (1.1 and 3.9 mg/dl), both radiopharmaceuticals gave similar results except for the moderate visualization of the urinary tract with DISIDA in contrast to JODIDA. In the remaining 11 patients with a total bilirubin level between 102 and 1303 mol/l (6 and 76 mg/dl), JODIDA showed significant advantages over DISIDA: non-visualization of the urinary tract, stronger and faster biliary contrast, and better gallbladder visualization. JODIDA thus offered substantial diagnostic advantages over DISIDA in 8 of these patients. In 4 patients, the differential diagnosis of jaundice (intrahepatic or mechanical disorder) was possible with JODIDA, whereas DISIDA either could not visualize intestinal or gallbladder activity at all or could not differentiate it from the urinary tract. In one patients, JODIDA offered faster (18 h) diagnosis. In the remaining 3 patients, other, substantially false interpretations could be avoided through the use of JODIDA. Further clinical experience with JODIDA in more than 40 patients confirmed the results of this study. We concluded that JODIDA is of significant advantage over DISIDA in clinical situations such as total bilirubin level above 80–100 mol/l (4.7 to 5.8 mg/dl), examination of small children and critically ill patients and suggestion of bile leakage. As there are also no clinical disadvantages, it could become the rediopharmaceutical of choice for hepatobiliary imaging.     

Tc-99m dextran: a new blood-pool-labeling agent for radionuclide angiocardiography

We have explored the possibility of imaging the cardiac blood pool with dextran (Dx) labeled with Tc-99m (Tc) after Sn2+ reduction. Stannous dextran (SnDx) kits were prepared in advance and labeling was performed by adding Tc-99m. The labeling efficiency was greater than 95%. Technetium-99m dextran (TcDx) was highly stable both in vivo and in vitro. In seven dogs we compared the quality of blood-pool images obtained with TcDx of different molecular weights (4 X 10(4) = Dx-40; 5 X 10(5) = Dx-500; 2 X 10(6) = Dx-2000) and with Tc-99m red blood cells (TcRBC) labeled in vitro, and determined the organ distribution of this new agent by whole-body scanning and blood sampling. TcDx provided high-quality cardiac blood-pool images up to 60 min after injection. The heart-to-lung ratios averaged 3.7 for TcDx-40, 3.9 for TcDx-500, and 5.4 for TcRBC at 60 min. Whereas TcDx-40 showed a relatively rapid initial urinary excretion and TcDx-2000 was degraded rapidly, TcDx-500 demonstrated the best kinetics for blood-pool imaging. Thus, TcDx is a new radiopharmaceutical with high labeling efficiency and stability. It overcomes a number of the limitations of currently used blood-labeling agents and may become useful for blood-pool imaging in man.