Two-step immunoscintigraphy for non-small-cell lung cancer staging using a bispecific anti-CEA/anti-indium-DTPA antibody and an indium-111-labeled DTPA dimer.
Immunoscintigraphy (IS) using anti-CEA F(ab')2 monoclonal antibody (MAb) is useful for improving mediastinal staging of nonsmall cell lung cancer (NSCLC), but the technique was limited because of an insufficient contrast between tumor and normal tissues. The aim of this study was to determine if the method could be improved by a two-step method which uses a bispecific anti-CEA/anti-di-DTPA antibody (Bs-MAb) and 111In-labeled di-DTPA-tyrosyl-lysine bivalent hapten.


METHODS
Twelve patients were intravenously given a 30 min Bs-MAb infusion (0.1 mg/kg). Four days later, they were injected intravenously with 0.1 microgram/kg hapten labeled with 185 MBq 111In (5 mCi). Images were recorded immediately and 6 and 24 hr after hapten injection. A pharmacokinetic analysis was performed. Surgery was performed 3 days after 111In-hapten injection, and samples of tumor and normal tissues were collected for immunohistochemical and biodistribution studies. IS results were classified as true-positive (TP), false-positive (FP), true-negative (TN) or false-negative (FN) according to the surgical data.


RESULTS
Primary tumors were visualized in nine patients. The contrast was excellent, generally higher than that obtained with direct labeling of anti-CEA. In the mediastinum, IS results were (after surgery) five TN, two TP and one FP. One case remains undetermined. The FP result was due to a Bs-MAb uptake in intrapulmonary lymph nodes. IS was in agreement with preoperative staging in six of these nine patients and discordant in three.


CONCLUSIONS
Our study confirmed that the two-step method with a bispecific antibody could greatly improve the performances of IS for lung cancer staging.
Vuillez
J P
JP
Department of Nuclear Medicine, CHU de Grenoble Centre Catherine de Sienne, Nantes, France.
Moro
D
D
Brichon
P Y
PY
Rouvier
E
E
Brambilla
E
E
Barbet
J
J
Peltier
P
P
Meyer
P
P
Sarrazin
R
R
Brambilla
C
C
D018033:Antibodies, Bispecific; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D006241:Haptens; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D008482:Mediastinum / Q000000981:diagnostic imaging; D009367:Neoplasm Staging; D004369:Pentetic Acid; D016719:Radioimmunodetection / Q000379:methods*; D012680:Sensitivity and Specificity
D018033:Antibodies, Bispecific; D002272:Carcinoembryonic Antigen; D006241:Haptens; D007205:Indium Radioisotopes; D004369:Pentetic Acid