Quantitative immuno-SPECT monitoring of pretargeted radioimmunotherapy with a bispecific antibody in an intraperitoneal nude mouse model of human colon cancer.
The prospects for using pretargeted immuno-SPECT to monitor the response to pretargeted radioimmunotherapy were examined. In this study, a bispecific anticarcinoembryonic antigen (CEACAM5; CD66e) × antihapten monoclonal antibody, TF2, was used in combination with a small (1.5 kD) peptide, IMP288, labeled with (111)In and (177)Lu.


METHODS
First, tumor uptake of (111)In-IMP288 and (177)Lu-IMP288, as determined by immuno-SPECT, was validated by ex vivo counting. Two groups of female BALB/c nude mice had LS174T tumors implanted in the peritoneal cavity. They received intravenous injections of TF2, followed by 10 MBq of (111)In-IMP288 or 90 MBq of (177)Lu-IMP288. A control group of non-tumor-bearing mice received TF2 and (111)In-IMP288. One hour after the radiolabeled IMP288 was given, small-animal SPECT/CT images were acquired, and subsequently animals were dissected. Furthermore, a survival study was performed in 3 groups of 10 mice with intraperitoneal tumors: mice received TF2 and (177)Lu-IMP288 (60 MBq), nonpretargeted (177)Lu-IMP288 (60 MBq), or phosphate-buffered saline. Immuno-SPECT scans were acquired directly after therapy and at 14 and 45 d after therapy. Tumor growth was analyzed in the successive scans in each animal.


RESULTS
(111)In- and (177)Lu-labeled IMP288 had similar in vivo distribution. The activity measured in the pretargeted immuno-SPECT images correlated well with the uptake measured in the dissected tumors (Pearson r = 0.99, P < 0.05). In the therapy study, the SPECT images showed rapid and selective tumor targeting with high tumor-to-background contrast (30 ± 12) as early as 1 h after injection. The successive images of the treated mice showed delayed tumor growth in the pretargeted radioimmunotherapy group, corresponding with their prolonged survival.


CONCLUSIONS
Pretargeted immuno-SPECT with TF2 and (111)In- or (177)Lu-IMP288 can be used to predict and confirm tumor targeting and monitor the therapeutic effect of pretargeted radioimmunotherapy.
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. r.schoffelen@nucmed.umcn.nl
Rafke
R
Schoffelen
Winette T A
WT
van der Graaf
Robert M
RM
Sharkey
Gerben M
GM
Franssen
William J
WJ
McBride
Chien-Hsing
CH
Chang
Desirée L
DL
Bos
David M
DM
Goldenberg
Wim J G
WJ
Oyen
Otto C
OC
Boerman
D000818:Animals; D018033:Antibodies, Bispecific / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D016719:Radioimmunodetection / Q000379:methods*; D016499:Radioimmunotherapy; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D016896:Treatment Outcome
D018033:Antibodies, Bispecific