Molecular Imaging of Insulin Growth Factor 1 Receptor Expression Is Effective for Triple-Negative Breast Cancer

The research was presented April 2010 at the 101st meeting of the American Association of Cancer Research in Washington, D.C., USA. The purpose of the study, conducted by researchers from Radboud University Nijmegen Medical Center (Nijmegen, The Netherlands), was to develop a noninvasive method of visualizing the insulin-like growth factor 1 receptor (IGF-1R), which is expressed by 30% - 40% of patients with triple-negative breast cancer, thus making them uniquely identifiable and able to be treated with IGF-1R antibodies.

"The use of molecular imaging techniques, such as PET and SPECT, has been helpful in the progression of our research toward finding molecular targets to visualize the IGF-1R, expressed by cells of patients with triple-negative breast cancer. In the future, the ability to visualize the receptor may enable more effective patient selection from the triple-negative breast cancer patient population for IGF-1R targeted therapy,” remarked Otto C. Boerman, of the department of nuclear medicine, Radboud University Medical Center, Nijmegen. Siemens Healthcare (Erlangen, Germany) Inveon PET and MILabs U-SPECT preclinical imagers were used in the in vivo portion of the study. Small animal PET, SPECT, and computed tomography (CT) molecular imaging provides quantitative insight into understanding tumor biology and can aid in the development of therapeutic options.

The researchers concluded that ¹¹¹In-R1507 SPECT and ⁸⁹Zr-R1507 PET are excellent methods to visualize IGF-1R expression in vivo in triple-negative breast cancer xenografts. The study results verified that ¹¹¹In-R1507 was slowly internalized by SUM149 cells and was accumulated specifically and efficiently in the SUM149 xenografts. The specific tumor uptake was reported at 20% ID/g, 33% ID/g, and 31% ID/g at one, three and seven days post injection, respectively. At the optimal dose for imaging, the tumor uptake was 35% ID/g and enabled clear visualization of the subcutaneous xenograft with increasing contrast at later time points.

The study was conducted using R1507, a monoclonal antibody directed against an epitope on the extracellular domain of the IGF-1R. It was radiolabeled with ¹¹¹Indium, ¹²⁵Iodine, and ⁸⁹Zirconium. In vitro, the affinity and internalization kinetics of ¹¹¹In-R1507 were determined using the IGF-1R expressing breast cancer cell line SUM149, which is estrogen receptor-, progesterone receptor-, and HER2 receptor-negative. In vivo studies were performed in BALB/c nude mice with subcutaneous SUM149 xenografts. To determine the pharmacodynamics of R1507, mice received an intravenous injection of ¹¹¹In-R1507 and ¹²⁵I-R1507. One, three, and seven days postinjection, ex vivo tumor uptake was measured. Nonspecific uptake was determined by coinjection of an excess unlabeled R1507. A dose escalation study was performed with ¹¹¹In-R1507 to determine the optimal protein dose of R1507 for in vivo imaging (dose range 1 µg - 1000 µg). Finally, PET and SPECT images were acquired of mice with subcutaneous SUM149 tumors one, three, and seven days postinjection of ⁸⁹Zr-R1507 and ¹¹¹In-R1507, respectively.

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Radboud University Nijmegen Medical Center
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