Radioimmunoguided surgery in colorectal cancer using a genetically engineered anti-CEA single-chain Fv antibody.
In radioimmunoguided surgery (RIGS), a radiolabeled antibody is given i.v. before surgery and a hand-held gamma-detecting probe is used to locate tumor in the operative field. The rapid blood clearance and good tumor penetration of single-chain Fv antibodies (scFv) offer potential advantages over larger antibody molecules used previously for RIGS. A Phase I clinical trial is reported on RIGS with scFv (MFE-23-his) to carcinoembryonic antigen (CEA). Thirty-four patients undergoing surgery for colorectal carcinoma (17 primary tumors, 16 liver metastases, and 1 anastomotic recurrence) and 1 patient with liver metastases of pancreatic carcinoma received 125I-labeled MFE-23-his scFv (125I-MFE-23-his) 24, 48, 72, or 96 h before operation. 125I-MFE-23-his showed biexponential blood clearance with alpha and beta half-lives of 0.32 and 10.95 h, respectively. The abdomen was scanned during surgery with a hand-held gamma detecting probe (Neoprobe Corp.). 125I-MFE-23-his showed good tumor localization; comparison with histology showed overall accuracy of 84%. Highest median ratios for tumor:normal tissue and tumor:blood were recorded 72 or 96 h after scFv injection for patients undergoing resection of liver metastases. High levels of radioactivity were found in the kidneys. Five patients had grade 1 fever, and three had a grade 1 rise in blood pressure according to the Common Toxicity Criteria. There was a significant correlation between these ratios and those measured in excised tissues using a laboratory gamma counter (P < 0.001). MFE-23-his scFv antibody localizes in CEA-producing carcinomas. The short interval between injection and operation, the lack of significant toxicity, and the relatively simple production in bacteria make MFE-23-his scFv suitable for RIGS.
Mayer
A
A
Department of Oncology, Royal Free and University College Medical School, University College London, United Kingdom.
Tsiompanou
E
E
O'Malley
D
D
Boxer
G M
GM
Bhatia
J
J
Flynn
A A
AA
Chester
K A
KA
Davidson
B R
BR
Lewis
A A
AA
Winslet
M C
MC
Dhillon
A P
AP
Hilson
A J
AJ
Begent
R H
RH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000235:genetics / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D004274:DNA, Recombinant / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005818:Genetic Engineering; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016719:Radioimmunodetection / Q000379:methods*; D014018:Tissue Distribution
D000906:Antibodies; D002272:Carcinoembryonic Antigen; D004274:DNA, Recombinant; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes; C055966:immunoglobulin Fv