67Copper-2-iminothiolane-6-[p-(bromoacetamido)benzyl-TETA-Lym-1 for radioimmunotherapy of non-Hodgkin's lymphoma.
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.
O'Donnell
R T
RT
Department of Internal Medicine, University of California Davis Medical Center, Sacramento 95816, USA.
DeNardo
G L
GL
Kukis
D L
DL
Lamborn
K R
KR
Shen
S
S
Yuan
A
A
Goldstein
D S
DS
Mirick
G R
GR
DeNardo
S J
SJ
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003301:Copper Radioisotopes / Q000627:therapeutic use*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage
D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; D006684:HLA-DR Antigens; D007074:Immunoglobulin G