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The advantages of the new, safer, but more expensive iodinated contrast agents are discussed, and opinions on which patient groups should receive the agents are presented. 相似文献
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Gerald L DeNardo Arutselvan Natarajan Saphon Hok Julie Perkins Monique Cosman Sally J DeNardo Felice C Lightstone Gary R Mirick Laird A Miers Rodney L Balhorn 《Journal of nuclear medicine》2007,48(8):1338-1347
Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting. 相似文献
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A modified technique for catheterization of the pulmonary artery was developed. It involves the passage of a tapered, movable-core, J-tipped guide wire across the right ventricle into the pulmonary artery followed by the advancement of a straightened Grollman pigtail catheter. The technique was successful in 34 of 34 pulmonary artery catheterizations. The method avoids prolonged catheter manipulation within the right ventricle. In addition, since the catheter does not cross the tricuspid valve until the guide wire has been advanced, the occasional complication of the pigtail "hooking" on a tricuspid valve leaflet or chordae tendineae during catheter withdrawal and manipulation is prevented. 相似文献
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乳腺管状小叶癌(Tubulolobular carcinoma,TLC)最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征,并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁(中位年龄60岁)。1例双侧乳腺受累,5例病变为多灶性。肿瘤直径0.5-2.5cm,色灰褐,质硬。组织学观察:TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂,且两者比例相当(统称为管状小叶模式)。 相似文献
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Lym-1, a monoclonal antibody (MAb) that preferentially targets malignant lymphocytes, has induced therapeutic remissions in patients with advanced non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) when labeled with iodine-131 (131I). Based on the strategy of fractionating the total radiation dose, trials were designed to define the safety, toxicity, and efficacy of a series of doses of 131I-Lym-1 given 2-6 weeks apart. All patients had disease resistant to standard therapy. 131I-Lym-1 was given after unconjugated Lym-1 and the 131I dose was escalated in Phase I-II trials. Therapy proved safe. The dose-limiting toxicity was thrombocytopenia. Nonhematological toxicities did not exceed grade 2 except for infrequent instances of grade 3 hypotension. In a low-dose (LD) trial of 131I-Lym-1, tumor regression occurred in 25 (83%) of 30 patients and 17 (57 %) had durable remissions; 3 of the remissions were complete. In a maximum tolerated dose (MTD) trial of 131I-Lym-1, 10 (71%) of 14 entries that received at least two doses of 131I-Lym-1 therapy and 11 (52%) of 21 total entries had remissions; 7 of the remissions were complete. All 3 entries in the MTD cohort of 100 mCi/m2 [3.7 MBq/m2] of body surface area had durable complete remissions. Therapeutic remission and human anti-mouse antibody (HAMA) after Lym-1 therapy were associated with increased survival that was significant in multivariate analyses. Evidence for an Ab3 idiotypic network with an antibody cytotoxic for Raji human lymphoma was found in the only patient examined in detail thus far; this patient was studied because she had a high titer, HAMA and prolonged survival. In conclusion, 131I-Lym-1 induced durable remissions in patients with chemotherapy-resistant NHL or CLL and was associated with acceptable toxicity. In a subset of the patients, survival was quite prolonged perhaps related to development of Ab3. 相似文献