In vitro adsorption of 99Tc(m)-MIBI, 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4- onto tubes

Adsorption of radiopharmaceuticals onto disposable syringes has been reported to amount to levels of almost 50%. Data on adsorption of radiopharmaceuticals onto materials used for in vitro studies are extremely limited. We assessed the extent of adsorption of 99Tc(m) hexakis(2-methoxyisobutylisonitrile) (99Tc(m)-MIBI), 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4 onto tubes used for in vitro measurement of cellular uptake of these radiopharmaceuticals. The influence on adsorption of different incubation media, temperature and time of incubation was evaluated. Total (not corrected for adsorption) uptake was compared with corrected, net cellular uptake in SK-BR-3, MCF-7 and liposarcoma cell lines. Values of adsorption ranging from 0.94+/-0.13% to 7.07+/-0.46% were found. The extent of adsorption of all the radiopharmaceuticals varied with the type of incubation medium and the incubation temperature. With 99Tc(m)-furifosmin, adsorption was dependent on the incubation time as well on the incubation temperature and some of the incubation media investigated. Our findings indicate that systematic investigations to evaluate the adsorption of radiopharmaceuticals onto materials used during in vitro studies of cellular uptake should be considered a mandatory aspect of quality control.     

心肌灌注显像剂^99mTc—tetrofosmin的临床前研究

对８名健康志愿者进行９９ｍＴｃｔｅｔｒｏｆｏｓｍｉｎ的临床前试验。采用一天或两天显像方案，行９９ｍＴｃｔｅｔｒｏｆｏｓｍｉｎ运动负荷和静息显像。通过采血和留尿测定药代动力学参数；采用全身扫描及感兴趣区等技术进行人体分布、靶／非靶比值、有效显像剂量和显像方案研究；依ＭＩＲＤ法估算各种用药情况下的内照射吸收剂量，进行辐射安全评价。结果：９９ｍＴｃｔｅｔｒｏｆｏｓｍｉｎ符合一次静脉给药的药代动力学二室模型，血药总清除率为１２７０ｍｌ／ｍｉｎ；心肌摄取较高，以百分注射剂量（％ＩＤ）为单位，给药后５分钟和６０分钟，运动负荷显像分别为３４０±０１３和２３６±０１９，静息显像则为３１１±１０２和２２２±０６８，前者摄取略高；在２７０～９２５ＭＢｑ给药剂量范围内，一天或两天方案的平面及ＳＰＥＣＴ显像图同样清晰，肝和肺本底低；内照射吸收剂量符合安全标准。临床前试验证明，９９ｍＴｃｔｅｔｒｏｆｏｓｍｉｎ安全有效，这为临床应用提供了依据。     

99Tcm-PnAO-硝基咪唑和99Tcm-HL91对乏氧心肌的实验研究

目的 探讨＾９９Ｔｃ＾ｍ－ＰｎＡＯ－硝基咪唑和＾９９Ｔｃ＾ｍ－ＨＬ９１２种乏氧心肌显像剂用于实验性心肌缺血、缺氧的作用。方法 进行小鼠体内分布与离体大鼠心脏模型研究,以９５％Ｏ２和５％ＣＯ２平衡的Ｋｒｅｂｓ－Ｈｅｎｓｅｌｅｉｔ缓冲液进行主动脉逆行灌注为对照组;以Ｎ２取代Ｏ２和ＣＯ２平衡的Ｋｒｅｂｓ－Ｈｅｎｓｅｌｅｉｔ缓冲液进行逆行灌注为乏氧组;以９５％Ｏ２和５％ＣＯ２平衡的Ｋｅｒｂｓ－Ｈｅｎｓｅｌ     

Direct 99m Tc labeling of Herceptin (trastuzumab) by 99m Tc(I) tricarbonyl ion.

By simply incubating Herceptin (trastuzumab) with [99m Tc(CO)3(OH2)3]+ ion in saline, a significant yield of 99m Tc-labeled trastuzumab was found to be achievable. The effective labeling may be based on that trastuzumab is inherent with endogenous histidine group to which 99m Tc(I) tricarbonyl ion can be strongly bound. For practical 99m Tc labeling processing, trastuzumab was purified beforehand from the commercial product, Herceptin (Genentech) via size exclusion chromatography to remove the excipient, alpha-histidine and a high-labeled yield could be obtained by incubating the purified trastuzumab with [99m Tc(CO)3(OH2)3]+. Retention of bioactivity of the 99m Tc(I)-labeled trastuzumab was validated using a cell binding test.     

Evaluation of [(99m)Tc] liposomes as lymphoscintigraphic agents: comparison with [(99m)Tc] sulfur colloid and [(99m)Tc] human serum albumin

This study investigates the use of [(99m)Tc] liposomes for the detection of sentinel lymph nodes. A variety of [(99m)Tc] liposome formulations were compared with common lymphoscintigraphic agents including [(99m)Tc] regular-sulfur colloid (SC), [(99m)Tc] 0.22 microfiltered-SC, [(99m)Tc] reduced heating time 0.22 microfiltered-SC, and [(99m)Tc] human serum albumin (HSA) in rabbits. Images were acquired for the first 60 minutes and at 24 hours, followed by tissue biodistribution study. All agents except [(99m)Tc] regular SC demonstrated good migration from the injection site. Agents were retained in the popliteal node at 24 hours to varying degrees as follows: both [(99m)Tc] filtered SC preparations > [(99m)Tc] regular SC > [(99m)Tc] liposomes > [(99m)Tc] HSA. [(99m)Tc] liposome imaging can be used to develop novel liposome compositions with improved lymph node diagnostic and drug delivery characteristics.     

Abnormal Tc99m sulesomab in Klippel-Trenaunay syndrome

Tc-99m sulesomab is indicated in bone and joint infection, but reading of scans can be affected by pre-existing conditions. This case report describes a case of Klippel-Trenaunay syndrome (KTS) which results in vascular malformations of one or more limbs. Tc-99m sulesomab imaging demonstrated persistent blood pool activity up to 20 hours post injection. However, despite this, septic arthritis could be identified with confidence in the same limb.     

Lymphoscintigraphy: a comparison of 99Tc(m) antimony sulphide colloid and 99Tc(m) stannous phytate.

In vitro comparison of 99Tc(m) antimony sulphide colloid and 99Tc(m) stannous phytate as well as in vivo studies in six rabbits and seven patients indicate disparity in the colloidal properties and localization of these two agents. The variability in lymphatic uptake and the relatively poor quality of scintigraphic images following interstitial injection of 99Tc(m) stannous phytate, when compared with 99Tc(m) antimony sulphide colloid, provide evidence of the unsuitability of this agent for lymphoscintigraphy. Maintenance of the diagnostic quality of the lymphoscintigraphic image and adherence to interpretive criteria already established therefore preclude the routine use of 99Tc(m) stannous phytate for interstitial lymphoscintigraphy.     

Use of (99m)Tc from a commercial (99)Mo/(99m)Tc generator as yield tracer for the determination of (99)Tc at low levels.

The concentrations of (99)Tc and impurity radionuclides in the (99m)Tc tracer solution obtained from a commercial (99)Mo/(99m)Tc generator were measured by gamma spectrometry and liquid scintillation counting. (99)Mo and (103)Ru were found in the (99m)Tc eluate. A simple separation using two extra alumina cartridges was investigated to purify the eluate to obtain a suitable (99m)Tc tracer with low (99)Tc concentration. The activity ratio of (99)Tc/(99m)Tc in the prepared (99m)Tc solution is lower than 15 x 10(-9), which is higher than the theoretical ratio of less than 10 x 10(-9). The possible reason is discussed. The (99)Tc in the 20 kBq spiked (99m)Tc tracer was found to be less than 0.3 mBq, which is lower than the detection limit of the radiometric method used for environmental samples. The purified (99m)Tc eluate is used as yield tracer for the determination of low levels of (99)Tc in environmental samples.     

Intracranial Tc99m MDP uptake in Sturge-Weber syndrome

A case of intracranial extraosseous 99mTc MDP uptake is presented, which was found on CT to be due to dystrophic gyral calcification characteristic of Sturge-Weber syndrome (SWS). The imaging characteristics of SWS are described. The possibility of extraosseous MDP uptake should be considered when unusual or atypical 'hot spots' are seen on bone scanning.     

Preclinical studies of [(99m)Tc]DTPA-mannosyl-dextran

We report the preclinical testing of a synthetic receptor-binding macromolecule, [(99m)Tc]DTPA-mannosyl-dextran (36 kDa, 8 DTPA and 55 mannosyl units per dextran, K(D) = 0.12 nM), for sentinel node detection. Nonclinical safety studies included cardiac pharmacology safety studies, acute toxicology and pathology studies at 50 and 500 times the scaled human dose in both rats and rabbits after foot pad administration, and perivascular irritation studies in rabbits following intra-muscular administration at 100 and 1000 times the scaled human dose. Biodistribution studies in rabbits at 15 m, 1 h, and 3 h indicated that [(99m)Tc]DTPA-mannosyl-dextran cleared the hind foot pad with a biological half-life of 2.21 +/- 0.27 h. Other than mild hepatocyte hypertrophy in rabbits, no abnormalities in toxicology or pathology were found. Intravenous administration had no effect on survival, any clinical observations, electrocardiograms, or blood pressures. Intramuscular injection had no effect on survival, clinical observations, injection site observations, or injection site histopathology. The estimated absorbed radiation dose to the affected breast was 0.15 mGy/MBq and the effective dose was 1.06 x 10(-2) mSv/MBq. This preclinical study demonstrates that [(99m)Tc]DTPA-mannosyl-dextran has no toxicities and has an acceptable biodistribution and radiation dose.