This study was performed to determine the maximum tolerated dose (MTD) and
therapeutic effects of
rhenium-186 ((186)Re)-labeled
liposomal doxorubicin (
Doxil), investigate associated toxicities, and calculate radiation absorbed dose in head and neck
tumor xenografts and normal organs.
Doxil and control
polyethylene glycol (PEG)-
liposomes were labeled using (186)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA) method.
Tumor-bearing rats received either no
therapy (n=6), intravenous
Doxil (n=4), or escalating radioactivity of (186)Re-Doxil (185-925 MBq/kg) or (186)Re-PEG-liposomes (1110-1665 MBq/kg) and were monitored for 28 days. Based on
body weight loss and systemic toxicity, MTD for (186)Re-Doxil and (186)Re-PEG-liposomes were established at injected radioactivity/
body weight of 740 and 1480 MBq/kg, respectively. (186)Re-injected radioactivity/
body weight for
therapy studies was determined to be 555 MBq/kg for (186)Re-Doxil and 1295 MBq/kg for (186)Re-PEG-liposomes. All groups recovered from their
body weight loss, leucopenia, and
thrombocytopenia by 28 days postinjection. Normalized radiation absorbed dose to
tumor was significantly higher for (186)Re-Doxil (0.299±0.109 Gy/MBq) compared with (186)Re-PEG-liposomes (0.096±0.120 Gy/MBq) (p<0.05). In a separate
therapy study,
tumor volumes were significantly smaller for (186)Re-Doxil (555 MBq/kg) compared with (186)Re-PEG-liposomes (1295 MBq/kg) (p<0.01) at 42 days postinjection. In conclusion, combination chemoradionuclide
therapy with (186)Re-Doxil has promising potential, because good
tumor control was achieved with limited associated toxicity.