Abstract 4927: 68Ga/177Lu-Peptide antagonist targeting of breast cancer: A xenograft evaluation
Authors: Rold Tammy L. , Berendzen Ashley F. , Bernskoetter Nicole E. , Rushin Jillian C. , Ma Lixin , Hoffman Timothy J. 
Published: May 2015

Abstract
Introduction: Recent progress in developing BB2r (bombesin receptor subtype 2) antagonist vectors with long term cellular retention has captured significant interest for in vivo targeting of BB2r positive tumor cells using diagnostic and therapeutic radioisotopes. Here we report on the evaluation of a 68Ga-labeled BB2r antagonist in comparison to 18F-FDG for selective PET imaging of BB2r expressing breast cancer xenografts. The theranostic potential of this BB2r antagonist vector is further explored by direct comparison of tumor targeting using the companion beta particle emitting 177Lu-labeled BB2r antagonist.
Methods: Breast tumor cell lines (T47D, MCF7, MB361, MB468, and MB231) were implanted in female SCID mice. ER+ cell line implanted mice were supplemented with 90 day release 17-beta Estradiol pellets (0.50 mg) one week prior to bilateral flank inoculations. 68Ga labeling of a commercially synthesized BB2r antagonist peptide, DOTA-Amino-Carboxymethyl-Piperidine-DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (Eur J Nucl Med Mol Imaging 38(1):97, 2011) was performed and the product verified to possess &gt; 95% purity by HPLC. Animals were administered 75-100uCi (2.77-3.7MBq) of 68Ga-BB2r antagonist and 200-300uCi (7.4-11.1MBq) of 18F-FDG on consecutive days with all PET imaging performed one hour post injection. Mice receiving 177Lu-BB2r antagonist 1.5-2.0mCi (55.5-74GBq) were imaged using Micro-SPECT/CT at 24hrs and 48hrs post injection (p.i.).
Results: The presence of the BB2r in each cell line was verified by Western blot analysis. 68Ga-BB2r antagonist uptake in xengorafts was observed in all breast tumor xenograft models and varied with the highest uptake being visualized in ER+ xenograft models. Concurrent 18F-FDG PET demonstrated relatively consistent glucose metabolism across all models. In all xenograft models requiring estradiol supplementation, prolonged bladder retention was observed. In the xenograft models administered 177Lu-BB2r antagonist, the tumor uptake at 1 hr p.i. was highest for ER+ models (7.12+1.92 %ID/g and 9.58+/-1.93 %ID/g for MCF7 and T47D xenografts, respectively) compared to 1.5+0.5%ID/g for the ER- MB231 xenograft model.
Conclusions: These preliminary findings suggest that PET imaging of BB2r expression in breast cancer models may be possible with preferential uptake in ER+ tumor cell lines. The preliminary theranostic data obtained using the analogous 177Lu-BB2r antagonist demonstrates the potential for in vivo delivery of targeted radiotherapeutics to BB2r expressing breast tumors.
Citation Format: Tammy L. Rold, Ashley F. Berendzen, Nicole E. Bernskoetter, Jillian C. Rushin, Lixin Ma, Timothy J. Hoffman. 68Ga/177Lu-Peptide antagonist targeting of breast cancer: A xenograft evaluation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4927. doi:10.1158/1538-7445.AM2014-4927