Imaging Biomarkers Predict Response to Anti-HER2 (ErbB2) Therapy in Preclinical Models of Breast Cancer

Abstract

Purpose: To evaluate noninvasive imaging methods as predictive biomarkers of response to trastuzumab in mouse models of HER2-overexpressing breast cancer. The correlation between tumor regression and molecular imaging of apoptosis, glucose metabolism, and cellular proliferation was evaluated longitudinally in responding and nonresponding tumor-bearing cohorts.

18F-FDG Small-Animal PET/CT Differentiates Trastuzumab-Responsive from Unresponsive Human Breast Cancer Xenografts in Athymic Mice

“…In the study by Kawada et al, changes in tumor uptake of 18 F-FDG PET in the responding patient were apparent 2 mo before tumor progression was confirmed by CT (19). In contrast, a preclinical study by Shah et al found no statistically significant changes in the tumor uptake of 18 F-FDG in HER2-overexpressing BT-474 BC xenografts or mouse mammary tumor virus/HER2 tumors after 1-3 wk of trastuzumab therapy (30). Interestingly, in our study there was a 31% reduction in the tumor uptake of 18 F-FDG in MDA-MB-361 HER2-overexpressing xenografts after 9 d of treatment; however, this difference was not statistically significant (P 5 0.32; Fig.…”

“…Furthermore, changes in tumor uptake of 111 In-DTPA-pertuzumab were informative on the decreased viability of tumor cells after 3 wk of trastuzumab therapy. Additionally, 39-deoxy-39-18 F-fluorothymidine, which accumulates in tumors in proportion to their proliferative properties and has shown promise in identifying early responding and nonresponding tumors in patients receiving chemotherapy, may be useful for monitoring response to trastuzumab (30,37).…”

Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging

“…18 F]FLT in humans and rodents (Chen et al, 2005;Shah et al, 2009). The number of Ki67-immunopositive cells evaluated in the SGZ of the DG in rats treated with CORT for 4 weeks was ϳ45% lower than that in the control group (Fig.…”

Tenascin-C: Exploitation and collateral damage in cancer management

“…Using probes coupled to fluorescent dyes or radioisotopes in vivo had been applied in preclinical models. 51,52 With regard to the use of monoclonal antibodies in diagnostic imaging and radiotherapy, it is important to obtain a good delivery of radiation into the tumor but at the same time a proper manipulation of blood halflife is needed to reduce the risk of deiodination, hence increased accumulation in the thyroid. 29 Such a technical advance was recently reported using radioisotopes Cu or Tc upon coupling to monoclonal antibodies against tenascin-C. 53,54 For that purpose, based on the previously described ligand "L," 55 an optimized phosphonated bifunctional chelate (BFC) "L*" was developed as a coordination site to ensure a covalent and stable complex formation between Cu(II) and the antibody.…”