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111In-Diethylenetriamine pentaacetic acid-human anti-insulin-like growth factor 1 receptor monoclonal antibody R1507

, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: February 3, 2011.

Chemical name:111In-Diethylenetriamine pentaacetic acid-human anti-insulin-like growth factor 1 receptor monoclonal antibody R1507
Abbreviated name:111In-DTPA-R1507, 111In-R1507
Agent category:Antibody
Target:Insulin-like growth factor 1 receptor (IGF-1R)
Target category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT), gamma imaging
Source of signal:111In
  • Checkbox In vitro
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Structure not available in PubChem.



Insulin-like growth factor 1 (IGF-1, 70 amino acids) is secreted by the liver and target tissues in response to growth hormone stimulation (1). IGF-1 plays an important role in cell growth and development. IGF-1 binds to IGF-1 receptor (IGF-1R) with ~1,000-fold higher affinity than to insulin receptor. IGF-1R is a transmembrane tyrosine kinase receptor and is also highly expressed in many human cancers (2). IGF-1R plays an important role in tumor proliferation, apoptosis, angiogenesis, and metastasis (3, 4). Triple negative breast tumors are negative for estrogen receptors, progesterone receptors, and HER2. Patients with triple negative breast tumors have a lower survival rate than patients with estrogen receptor- or HER2-positive breast tumors (5). IGF-1R is overexpressed in 36% of all triple negative breast carcinomas (6).Therefore, monitoring of IGF-1R expression in breast tumor lesions with a non-invasive imaging modality is important for development of therapeutic treatments of these patients with anti-IGF-1R monoclonal antibodies (7). The human anti-IGF-1R monoclonal antibody R1507 is directed against the extracellular domain of human IGF-1R (8). In this chapter, Heskamp et al. (9) radiolabeled the human anti-IGF-1R monoclonal antibody R1507 with 111In for in vivo imaging of IFG-1R expression with single-photon emission computed tomography (SPECT). 111In-Diethylenetriamine pentaacetic acid-human anti-IGF-1R monoclonal antibody R1507 (111In-DTPA-R1507) has been evaluated in a triple negative breast cancer model in mice.



R1507 was conjugated with 10-fold molar excess of isothiocyanatobenzyl-DTPA in 0.1 M NaHCO3 (pH 9) for 60 min at room temperature (9). A solution of 244 MBq (6.6 mCi) 111InCl3 and 0.15 nmol DTPA-R1507 was incubated in buffer (pH 5–6) for 30 min at room temperature. 111In-DTPA-R1507 was purified with column chromatography. 111In-DTPA-R1507 exhibited a radiochemical purity of >98% with a labeling efficiency of >95%. The immunoreactivity of 111In-DTPA-R1507 was 99%. The number of DTPA groups per antibody was not reported.

In Vitro Studies: Testing in Cells and Tissues


Heskamp et al. (9) reported that the parent antibody R1507 exhibited 50% inhibitory concentration (IC50) values of 0.08–0.12 nM for IGF-1R on the triple negative human breast cancer cell line SUM149. 111In-DTPA-R1507 was mainly membrane-bound in the early hours of incubation and then was gradually internalized until 62% of the surface-bound radioactivity was internalized at 48 h after incubation.

Animal Studies



Heskamp et al. (9) performed ex vivo biodistribution studies in nude mice (n = 6/group) bearing the triple negative breast SUM149 xenografts with injection of 0.2 MBq (0.005 mCi, 3.3 pmol) 111In-DTPA-R1507 and co-injection with 6.6 pmol to 6.6 nmol unlabeled R1507. The optimal doses of R1507 for radioactivity accumulation in the tumors were 6.6 pmol and 19.8 pmol at 3 d after injection with 38% and 35% injected dose/gram (ID/g), respectively. For doses of 66 pmol or higher, tumor accumulation was <15% ID/g. The blood and muscle concentrations were ~15% ID/g and ~1% ID/g, respectively, at all doses. All the other major organs showed <10% ID/g at all doses. Therefore, only the tumors showed specific binding. In another experiment, 0.4 MBq (0.11 mCi) 111In-DTPA-R1507 (3.3 pmol) showed tumor accumulation of 20 ± 6% ID/g, 33 ± 6% ID/g, and 31 ± 4% ID/g at 1, 3, and 7 d after injection, respectively. Co-injection of 3.3 nmol R1507 reduced the tumor uptake to 5.6% ID/g at 7 d. The tumor/blood (3.8) and tumor/liver (12) ratios were highest at 7 d. In comparison, 125I-R1507 showed the highest tumor/blood (0.7) and tumor/liver (3.3) ratios at 3 d with a tumor uptake of 7% ID/g.

SPECT imaging in nude mice (n = 5) with 17.2 MBq (0.46 mCi, 10.4 pmol) 111In-DTPA-R1507 visualized the SUM149 tumor as early as 24 h after injection with a maximum contrast at 7 d. The tumor/liver ratio increased from 1.9 at 1 d to 5.8 at 7 d. Co-injection with excess R1507 (6.6 nmol) prevented the visualization of the tumor with the tumor/liver ratio of 1.5 at 7 d. Non-specific accumulation was observed in the liver, spleen, and salivary glands.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.


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