Radioimmunotherapy of metastatic colorectal tumours with iodine-131-labelled antibody to carcinoembryonic antigen: phase I/II study with comparative biodistribution of intact and F(ab')2 antibodies.
Studies in animal tumour models of colorectal cancer suggest that F(ab')2 antibody fragments to carcinoembryonic antigen (CEA) labelled with iodine-131 give superior therapy compared with intact anti-CEA antibody. The purpose of this study was to investigate this hypothesis in patients. Ten patients received intact A5B7 IgG1 mouse monoclonal antibody (MAb) to CEA and nine patients received the F(ab')2 fragment of the same antibody. The biodistribution for each molecule was compared using quantitative single-photon emission computerised tomographic (SPECT) gamma-camera imaging. Tumour responses were seen in both groups and myelosuppression was the limiting toxicity. F(ab')2 localised more rapidly than intact antibody in tumour, giving a mean percentage injected activity per kg at 4.25 h after injection of 8.2% for F(ab')2 compared with 4.4% for intact antibody (P < 0.05). No significant difference in antibody clearance from, or cumulative dose per unit administered activity (cGy MBq-1) to, tumour was seen. Distribution in blood was similar for both the intact and fragment antibody. These findings are consistent with more rapid penetration of the smaller F(ab')2 into tumour masses. More efficient early uptake will give higher maximum dose rates to the tumour which is valuable for radioimmunotherapy (RIT) when low dose rates may limit effectiveness of treatment. F(ab')2 fragments may provide a substantially enhanced method of delivering RIT.
Lane
D M
DM
Department of Clinical Oncology, Royal Free Hospital School of Medicine, London, UK.
Eagle
K F
KF
Begent
R H
RH
Hope-Stone
L D
LD
Green
A J
AJ
Casey
J L
JL
Keep
P A
PA
Kelly
A M
AM
Ledermann
J A
JA
Glaser
M G
MG
D000328:Adult; D000368:Aged; D002272:Carcinoembryonic Antigen / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D005260:Female; D006207:Half-Life; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D000922:Immunotoxins / Q000378:metabolism* / Q000627:therapeutic use* / Q000633:toxicity; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy; D014018:Tissue Distribution
D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D007457:Iodine Radioisotopes