ImmunoSPECT and immunoPET of IGF-1R expression with the radiolabeled antibody R1507 in a triple-negative breast cancer model.
The insulinlike growth factor 1 receptor (IGF-1R) is a new target for the treatment of breast cancer. Patients with breast cancer lesions that express IGF-1R may benefit from treatment with anti-IGF-1R antibodies. Therefore, the aim of the present study was to develop a noninvasive, in vivo imaging method, using radiolabeled antibodies, to visualize IGF-1R expression.


METHODS
R1507 is a monoclonal antibody directed against the IGF-1R. In vitro, the affinity and internalization kinetics of (111)In-R1507 were determined using the IGF-1R-expressing triple-negative breast cancer cell line SUM149. In vivo, the pharmacodynamics of (111)In-R1507 and (125)I-R1507 were determined in mice with subcutaneous SUM149 tumors. (111)In-R1507 SPECT and (89)Zr-R1507 PET images of mice with subcutaneous SUM149 tumors were acquired at 1, 3, and 7 d after injection.


RESULTS
(111)In-R1507 (concentration required to inhibit binding by 50%, 0.1 nM) was slowly internalized by SUM149 cells. (111)In-R1507 specifically and efficiently accumulated in the SUM149 xenografts: the tumor uptake was 20 percentage injected dose per gram (%ID/g), 33 %ID/g, and 31 %ID/g at 1, 3, and 7 d after injection, respectively. (125)I-R1507 accumulated in the tumor less efficiently. Small-animal SPECT and small-animal PET of mice clearly visualized the subcutaneous SUM149 xenograft, with increasing contrast at later time points.


CONCLUSIONS
(111)In-R1507 and (89)Zr-R1507 are new tracers to noninvasively determine IGF-1R expression in vivo in breast cancer xenografts using SPECT and PET. In the future, these techniques may enable patient selection for IGF-1R-targeted therapy.
Heskamp
Sandra
S
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. s.heskamp@nucmed.umcn.nl
van Laarhoven
Hanneke W M
HW
Molkenboer-Kuenen
Janneke D M
JD
Franssen
Gerben M
GM
Versleijen-Jonkers
Yvonne M H
YM
Oyen
Wim J G
WJ
van der Graaf
Winette T A
WT
Boerman
Otto C
OC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D016719:Radioimmunodetection / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017526:Receptor, IGF Type 1 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019275:Radiopharmaceuticals; D017526:Receptor, IGF Type 1; C551399:teprotumumab