Pretargeted radioimmunoscintigraphy in patients with primary colorectal cancer using a bispecific anticarcinoembryonic antigen CEA X anti-di-diethylenetriaminepentaacetic acid F(ab')2 antibody.
BACKGROUND
Antibody-based imaging agents are available commercially, but their success has been limited, mainly because of low contrast and the emergence of 2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scanning. In pretargeting, administration of the radionuclide is separated from the antibody, thereby enhancing image contrast and allowing detection at earlier time points after injection.


METHODS
The authors conducted an open-label, single-arm trial that assessed a pretargeting procedure in which an anticarcinoembryonic antigen x (anti-CEA x) anti-diethylenetriaminepentaacetic acid (anti-DTPA)-indum (In) antibody was used in combination with a (111)In-labeled di-DTPA peptide for the diagnostic imaging of CEA-expressing colorectal cancer. Three patients received the (111)In peptide alone to investigate tumor targeting, organ distribution, and clearance of the peptide. Thereafter, 11 patients received the bispecific antibody (bsAb) (5 mg) to pretarget the tumor. After 3 to 5 days, patients were injected with 185 megabecquerels of (111)In-labeled peptide to assess the optimal interval for best image quality.


RESULTS
Fourteen patients with primary colorectal cancer were enrolled. One of 3 patients who received (111)In peptide alone had low-level tumor uptake. In 9 of 11 other patients, tumors were observed. In 1 patient, FDG-PET-positive lymph nodes were observed clearly with pretargeted immunoscintigraphy. Peptide pharmacokinetics revealed enhanced circulating levels of (111)In-labeled peptide in patients in the 3-day interval cohort compared with the other cohorts. Tumor-to-background ratios ranged from 3.5 to 6.4 in the 3-day interval group, from 5.1 to 14.2 in the 4-day interval group, and from 3.5 to 3.9 in the 5-day interval group. The best images were acquired with a 4-day interval at 24 hours after injection of the radiolabeled peptide. Grade 1 adverse events were observed in 2 patients.


CONCLUSIONS
Imaging of colorectal cancer using a 2-step, pretargeting system produced the best imaging results 24 hours after peptide administration using a 4-day interval between injection of the bsAb and the peptide.
Aarts
Frits
F
Department of Surgery, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands. f.aarts@chir.umcn.nl
Boerman
Otto C
OC
Sharkey
Robert M
RM
Hendriks
Thijs
T
Chang
Chien-Hsing
CH
McBride
William J
WJ
Bleichrodt
Robert P
RP
Oyen
Wim J G
WJ
Goldenberg
David M
DM
D000368:Aged; D000369:Aged, 80 and over; D018033:Antibodies, Bispecific; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging*; D005240:Feasibility Studies; D005260:Female; D006241:Haptens; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D008297:Male; D008875:Middle Aged; D004369:Pentetic Acid / Q000276:immunology*; D016719:Radioimmunodetection / Q000009:adverse effects / Q000379:methods*; D011971:Receptors, Immunologic
D018033:Antibodies, Bispecific; C548518:CEA X protein, human; D002272:Carcinoembryonic Antigen; C052643:F(ab')2 receptor; D006241:Haptens; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D011971:Receptors, Immunologic; D004369:Pentetic Acid