Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507.
OBJECTIVE
To investigate whether indium-111-labeled R1507 ((111)In-R1507) immuno-SPECT (single-photon emission computed tomography), a novel noninvasive, in vivo screening method to visualize membranous insulin-like growth factor 1 receptor (IGF-1R) expression and accessibility, can be used to predict IGF-1R treatment (R1507) response in bone sarcomas.


METHODS
BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human bone sarcoma xenografts (OS-1, EW-5, and EW-8) which showed high, modest, or no response, respectively, to R1507, a monoclonal antibody targeting the extracellular domain of IGF-1R. An IGF-1R-negative tumor (OS-33), unresponsive to IGF-1R inhibitors, was examined as well. Mice were injected with (111)In-R1507. Biodistribution and immuno-SPECT/computed tomography imaging studies were carried out 1, 3, and 7 days p.i. in mice with OS-1 and EW-5 xenografts and 3 days p.i. in mice with EW-8 and OS-33 xenografts.


RESULTS
Biodistribution studies showed specific accumulation of (111)In-R1507 in OS-1 and EW-5 xenografts (27.5 ± 6.5%ID/g and 14.0 ± 2.8%ID/g, 3 days p.i., respectively). Most importantly, (111)In-R1507 uptake in IGF-1R positive, but unresponsive, EW-8 xenografts (6.5 ± 1.5%ID/g, 3 days p.i.) was similar to that of the IGF-1R-negative OS-33 tumor (5.5 ± 0.6%ID/g, 3 days p.i.). Uptake in normal tissues was low and nonspecific. Corresponding immuno-SPECT images clearly discriminated between high, modest, and nonresponding tumors by showing a homogeneous (OS-1), heterogeneous (EW-5), or nonspecific (EW-8 and OS-33) tumor uptake of (111)In-R1507.


CONCLUSIONS
(111)In-R1507 immuno-SPECT is an excellent method to visualize membranous IGF-1R expression and target accessibility in vivo in human bone sarcoma xenografts and may serve as an independent marker to predict IGF-1R therapy (R1507) response in bone sarcoma patients.
Departments of Medical Oncology and Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. E.Fleuren@onco.umcn.nl
Emmy D G
ED
Fleuren
Yvonne M H
YM
Versleijen-Jonkers
Addy C M
AC
van de Luijtgaarden
Janneke D M
JD
Molkenboer-Kuenen
Sandra
S
Heskamp
Melissa H S
MH
Roeffen
Hanneke W M
HW
van Laarhoven
Peter J
PJ
Houghton
Wim J G
WJ
Oyen
Otto C
OC
Boerman
Winette T A
WT
van der Graaf
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015203:Reproducibility of Results; D012509:Sarcoma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007205:Indium Radioisotopes; D017526:Receptor, IGF Type 1; C551399:teprotumumab