Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radioimmunotherapy has shown promising results for treatment of radiosensitive malignancies such as lymphoma. Positive responses have been reported in patients with non-Hodgkin's lymphoma treated with 131I-radiolabeled Lym-1, a mouse anti-lymphoma monoclonal antibody. In this study, the efficacy of 67Cu-radiolabeled Lym-1 was examined. Nude mice bearing human Burkitt's lymphoma (Raji) tumors (20-524 mm3) were treated with 12.4, 14.8, 18.5, and 23.3 MBq of 67Cu-2IT-BAT-Lym-1. Tumor size was measured to assess efficacy, and mouse weight, blood counts, and mortality were monitored to assess toxicity. In mice treated with 12.4, 14.8, and 18.5 MBq of 67Cu-2IT-BAT-Lym-1, 50% (9 of 18), 42% (5 of 12), and 50% (3 of 6) of tumors achieved remission or cure; 33% of tumors were cured overall; and significant regrowth delay was observed. The 23.3 MBq dose group did not yield meaningful efficacy data because of high mortality. In control groups receiving 14.8 and 18.5 MBq of the isotype-matched nonspecific monoclonal antibody radioimmunoconjugate, 67Cu-2IT-BAT-L6, 0% (0 of 15) and 17% (2 of 12) of tumors achieved a response; hence, targeted delivery of radiation was the dominant antitumor mechanism of 67Cu-2IT-BAT-Lym-1. LD50/30 for mice treated with 67Cu-2IT-BAT-Lym-1 and -L6 were 21.6 and 20.6 MBq, respectively. In conclusion, 67Cu-2IT-BAT-Lym-1 provided a therapeutic and frequently curative dose of radiation to tumored mice with modest toxicity.
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PMID:Efficacy and toxicity of 67Cu-2IT-BAT-Lym-1 radioimmunoconjugate in mice implanted with human Burkitt's lymphoma (Raji). 981 40

Copper-67 (67Cu) has ideal properties for radioimmunotherapy. The 62-h half-life is similar to the residence time of antibodies in tumor, and the therapeutic beta emission of 67Cu is comparable to that of 131I. 67Cu, however, has gamma emissions similar to 99mtechnetium that are favorable for imaging. The macrocyclic chelating agent 1,4,7,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (TETA) binds 67Cu tightly and selectively, facilitating linkage to Lym-1, a mouse monoclonal antibody that preferentially targets malignant lymphocytes. The safety, efficacy, and practicality of 67Cu-2-iminothiolane (2IT)-6-[p-(bromoacetamido)benzyl]-TETA (BAT)-Lym-1 was assessed in this Phase I/II clinical trial for patients with non-Hodgkin's lymphoma (NHL) who had failed standard therapy. Up to four doses of 67Cu-2IT-BAT-Lym-1, 25 or 50-60 mCi/m2/dose (0.93 or 1.85-2.22 GBq/m2/dose, respectively) were administered; the lower dosage was used when NHL was detected in the bone marrow. 67Cu-2IT-BAT-Lym-1 provided good imaging of NHL, had favorable radiation dosimetry, and had a response rate of 58% (7 of 12). Hematological toxicity was dose-limiting, but no significant nonhematological toxicity was observed. The ability to image and treat NHL patients with a single radiopharmaceutical with useful physical properties makes 67Cu-labeled monoclonal antibody an option for future clinical trials, as this study showed that 67Cu-2IT-BAT-Lym-1 was safe, effective, and practical.
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PMID:67Copper-2-iminothiolane-6-[p-(bromoacetamido)benzyl-TETA-Lym-1 for radioimmunotherapy of non-Hodgkin's lymphoma. 1054 82

Radioimmunotherapy using radiolabeled monoclonal antibodies against tumor-associated antigens has been efficacious, particularly in the treatment of radiosensitive malignancies such as lymphoma. Antilymphoma monoclonal antibody Lym-1, labeled with copper-67 ((67)Cu), iodine-131 ((131)I), or yttrium-90 ((90)Y), has been effective salvage therapy for patients with non-Hodgkin's lymphoma. Although (131)I has had the dominant role in radioimmunotherapy thus far, several properties of radiometals are preferable. A total of 70 patients with B-lymphocytic non-Hodgkin's lymphoma were studied using (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, or (111)In-2IT-BAD-Lym-1. Because (90)Y does not have good emissions for imaging, indium-111 ((111)In), its analogue, was used as a surrogate to estimate (90)Y-2IT-BAD-Lym-1 pharmacokinetics and radiation dosimetry. Subsets of four patients in each group received (67)Cu- and (131)I-labeled Lym-1 or (111)In- and (131)I-labeled Lym-1, allowing direct comparisons of the radioimmunoconjugates. Sequential blood samples and planar images were used to quantitate radioimmunoconjugate in tissues in order to determine pharmacokinetics and radiation dosimetry. (67)Cu-2IT-BAT-Lym-1 and (90)Y-2IT-BAD-Lym-1 exhibited higher cumulated activity concentrations and radiation absorbed doses per unit of administered radioactivity for tumors than did (131)I-Lym-1. The mean tumor cumulated activity (area under the time-activity curve) concentrations per unit of administered radioactivity for (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, and (90)Y-2IT-BAD-Lym-1 were 96.89, 33.96, and 43.42 GBq-s/GBq/g, respectively. The mean tumor radiation doses from (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, and (90)Y-2IT-BAD-Lym-1 were 2.5, 1.0, and 6.6 Gy/GBq, respectively, because (90)Y deposits more radiation per unit of administered radioactivity. Per unit of administered radioactivity, radiation doses from (67)Cu-2IT-BAT-Lym-1 and (131)I-Lym-1 to normal tissues were similar except that the liver received a higher dose from (67)Cu-2IT-BAT-Lym-1 than from (131)I-Lym-1; radiation doses to normal tissues from (90)Y-2IT-BAD-Lym-1 were generally higher. Consequently, the therapeutic indices (ratio of radiation doses to tumor and normal tissues) for (67)Cu-2IT-BAT-Lym-1, and less generally for (90)Y-2IT-BAD-Lym-1, were more favorable when compared to those for (131)I-Lym-1. Data from the matched subsets of patients showed similar therapeutic indices to those for the groups of patients. (67)Cu-2IT-BAT-Lym-1 showed more potential than (131)I-Lym-1 or (90)Y-2IT-BAD-Lym-1 for non-Hodgkin's lymphoma radioimmunotherapy.
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PMID:Are radiometal-labeled antibodies better than iodine-131-labeled antibodies: comparative pharmacokinetics and dosimetry of copper-67-, iodine-131-, and yttrium-90-labeled Lym-1 antibody in patients with non-Hodgkin's lymphoma. 1170 20