title: A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for non-Hodgkin's lymphoma.
abstract: Encouraged by the results of 131I-Lym-1 therapy trials for patients with B-cell non-Hodgkin's lymphoma (NHL), this phase I/II clinical trial of 67Cu-2IT-BAT-Lym-1 was conducted in an effort to further improve the therapeutic index of Lym-1-based radioimmunotherapy. Lym-1 is a mouse monoclonal antibody that preferentially targets malignant lymphocytes. 67Cu has beta emissions comparable to those of 131I but has gamma emissions more favorable for imaging. The macrocyclic chelating agent 1,4,7,11-tetraazacyclotetradecane-N,N',N",N"'-tetraacetic acid binds 67Cu tightly to form a stable radioimmunoconjugate in vivo.
  
  
  METHODS
  All 12 patients had stage III or IV NHL that had not responded to standard therapy; 11 had intermediate- or high-grade NHL. At 4-wk intervals, patients received up to four doses of 67Cu-2IT-BAT-Lym-1, 0.93 or 1.85-2.22 GBq/m2 (25 or 50-60 mCi/m2), with the lower dose used when NHL was detected in the bone marrow.
  
  
  RESULTS
  67Cu-2IT-BAT-Lym-1 provided good imaging of NHL and favorable radiation dosimetry. The mean radiation ratios of tumor to body and tumor to marrow were 28:1 and 15:1, respectively. Tumor-to-lung, -kidney and -liver radiation dose ratios were 7.4:1, 5.3:1 and 2.6: 1, respectively. This 67Cu-2IT-BAT-Lym-1 trial for patients with chemotherapy-resistant NHL had a response rate of 58% (7/12). No significant nonhematologic toxicity was observed. Hematologic toxicity, especially thrombocytopenia, was dose limiting.
  
  
  CONCLUSIONS
  67Cu remains an option for future clinical trials. This study established 67Cu-2IT-BAT-Lym-1 as a safe, effective treatment for patients with NHL.
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: O'Donnell
authors.forename: G L
authors.initials: GL
authors.lastname: DeNardo
authors.forename: D L
authors.initials: DL
authors.lastname: Kukis
authors.forename: K R
authors.initials: KR
authors.lastname: Lamborn
authors.forename: S
authors.initials: S
authors.lastname: Shen
authors.forename: A
authors.initials: A
authors.lastname: Yuan
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: C E
authors.initials: CE
authors.lastname: Carr
authors.forename: G R
authors.initials: GR
authors.lastname: Mirick
authors.forename: S J
authors.initials: SJ
authors.lastname: DeNardo
mesh_terms: D001853:Bone Marrow / Q000528:radiation effects; D005260:Female; D006571:Heterocyclic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage
chemical_list: D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C097568:copper-67-2IT-BAT-Lym-1