Radioimmunotherapy with a 64Cu-labeled monoclonal antibody: a comparison with 67Cu.

Abstract

ABSTRACT67Cu (tl2 = 62 h) has demonstrated potential as a radionuclide for radioimmunotherapy, but limited availability severely restricts its widespread use. 6"Cu (t1l2 = 12.8 h)has been shown to have comparable effectiveness in vitro and in vivo. The present study was undertaken to examine the therapeutic potential of 64Cu-and 67Cu-bromoacetamidobenzyl-1,4,8,1 1-tetraazacyclotetradecane-N,N',N",N'"-tetraacetic acid (BAT)-2-iminothiolane (2IT)-1A3 (1A3 is a mouse anti-human colorectal cancer mAb) for treatment of GW39 human colon carcinoma carried in hamster thighs. Hamsters were injected with 64Cu-or 67Cu-BAT-21T-1A3 or Cu-labeled nonspecific IgG (MOPC) or saline. Hamsters were killed 6-7 months after therapy or when tumors were 210 g. Of the hamsters with small tumors (mean weight 0.43 ± 0.25 g), 87.5% were disease-free 7 months after treatment with 2 mCi (1 Ci = 37 GBq) of 64Cu-BAT-21T-1A3 or 0.4 mCi of 67Cu-BAT-2IT-1A3. The mean tumor doses at these activities of 64Cu-and 67Cu-BAT-21T-lA3 were 586 and 1269 rad (1 rad = 0.01 Gy), respectively. In contrast, 76% of hamsters treated with 2 mCi of 64Cu-BAT-21T-MOPC or 0.4 mCi of 67Cu-BAT-2IT-MOPC had to be killed before 6 months because of tumor regrowth. When hamsters with larger tumors (mean weight 0.66 + 0.11 g) were treated with 64Cu-or 67Cu-BAT-21T-lA3, survival was extended compared with controls, but only one animal remained tumor-free to 6 months. These results demonstrate that 64Cu-and 67Cu-BAT-21T-1A3 given in a single administered dose can eradicate small tumors without significant host toxicity, but additional strategies to deliver higher tumor doses will be needed for larger tumors.

Comparison of 64Cu-Complexing Bifunctional Chelators for Radioimmunoconjugation: Labeling Efficiency, Specific Activity, and in Vitro/in Vivo Stability

“…Numerous chelators have been reported for complexing copper [5][6][7][8][9][10][11][12][13][14][15][16] and several of these have been functionalized to allow attachment to antibodies [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and are now commercially available. The choice of antibody/BFC combination will affect efficacy as an imaging or therapy agent.…”

In vivo evaluation of PEGylated 64Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

“…PET isotopes such as 18 F, 15 O, 13 N and 11 C have relative short half-lives where only early imaging time-points are possible, leaving biological processes with duration of several hours or days impossible to explore [11]. Tumor imaging using the longer lived PET isotope 64 Cu, with favorable decay characteristics (12.7 h), permit studies for as long as 48 h after injection [12,13]. Isotopes emitting beta-radiation for short-range local radiation therapy can be used for treatment of tumors if the radioisotopes can be targeted specifically to the diseased tissue.…”

“…FDG is mainly suitable for diagnosing tumors with high proliferative activity [1,6] and has limited diagnostic value for several cancer forms such as highly differentiated neuroendocrine (NE) [7,8] and prostatic tumors [9,10]. PET isotopes such as 18 F, 15 O, 13 N and 11 C have relative short half-lives where only early imaging time-points are possible, leaving biological processes with duration of several hours or days impossible to explore [11]. Tumor imaging using the longer lived PET isotope 64 Cu, with favorable decay characteristics (12.7 h), permit studies for as long as 48 h after injection [12,13].…”

Monte Carlo N-Particle (MCNP) Modeling of the Cellular Dosimetry of64Cu: Comparison with MIRDcell S Values and Implications for Studies of Its Cytotoxic Effects

“…In addition to its positron emission, 64 Cu emits b 2 particles, Auger and internal conversion (IC) electrons, and g-photons. The b 2 particles and Auger electrons of 64 Cu have been studied for radiation treatment of tumors (5)(6)(7)(8)(9). The maximum b 2 energy of 64 Cu is 0.579 MeV (40%) (10).…”