Abstract 4537: Evaluation of a Lu-177 BB2r antagonist in a breast cancer model.
Authors: Rold Tammy , Richmond Kelsey , Szczodroski Ashley , Ma Lixin , Hoffman Timothy J. 
Published: August 2014

Abstract
Introduction:
The American Cancer Society estimates 229,060 new cases will be diagnosed and almost 40,000 deaths will occur this year due to breast cancer. The development of receptor targeted radiopharmaceuticals to accurately treat breast cancer at earlier stages will potentially result in an increased number of cancer survivors. This project evaluates the ability of a Lutetium-177 (Lu-177) labeled radiopharmaceutical to target the BB2 receptor (BB2r) in an estrogen receptor positive (ER+) human cancer cell line (T47D) SCID mouse model. The theranostic potential of this Lu-177 labeled peptide will be further assessed using concurrent preclinical SPECT/CT.
Methods:
Female SCID mice were supplemented with 60 day release 17-beta Estradiol pellets (0.50 mg) approximately one week prior to bilateral flank cell inoculations using 5 million T47D human breast cancer cells. The BB2r antagonist peptide, DOTA-Amino-Carboxymethyl-Piperidine-DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (Eur J Nucl Med Mol Imag, 38:97, 2011) was synthesized by solid phase peptide synthesis and verified by mass spectral analysis. The peptide was radiolabeled with Lu-177 and peak purified using RP-HPLC. Biodistribution and Micro-SPECT/CT studies were performed 10-12 weeks post cell inoculation. For the biodistribution data collection, animals were administered 25-30 uCi (0.93-1.11MBq) of Lu-177 BB2r antagonist in a volume of 100uL and collections were completed at 1hr, 4hr, 24hr, and 48hr post injection. Samples were weighed and residual radioactivity quantitated using a NaI well counter and data was reported as %ID/g. Micro-SPECT/CT studies were performed at 24hr and 48hr post injection (pi) of approximately 1 mCi (37 MBq) of Lu-177 BB2r antagonist.
Results:
As evidenced by biodistribution data, Lu-177 BB2r antagonist targeted ER+ flank tumors with 9.58±1.93%ID/g at 1 hr and was retained for prolonged time periods (up to 48hrs pi) with 3.99±1.13%ID/g. Pancreas uptake of the Lu-177 BB2r antagonist was determined to be 29.72±3.97 %ID/g at 1hr and demonstrated a rapid washout with 5.11±2.14%ID/g, 0.60±0.26%ID/g, and 0.37±0.18%ID/g at 4hr, 24hr, and 48hr, respectively. Highly desirable lack of kidney accumulation was observed with 3.06±0.29%ID/g, 2.18±0.60%ID/g, 1.41±0.33%ID/g, and 1.13±0.19%ID/g at 1hr, 4hr, 24hr, and 48hr, respectively. Micro-SPECT/CT data directly correlated with the biodistribution results demonstrating clear delineation of BB2r positive flank xenografts at 24hr and 48hr post radiopharmaceutical administration.
Conclusions:Using a Lu-177 labeled BB2r antagonist, we have demonstrated selective tumor targeting and prolonged retention characteristics in a preclinical model of ER+ human breast cancer confirmed by both biodistribution and SPECT/CT molecular imaging. These results strongly support expansion of this work to other breast cancer cell lines and further evaluation of this agent as a potential theranostic agent.
Citation Format: Tammy Rold, Kelsey Richmond, Ashley Szczodroski, Lixin Ma, Timothy J. Hoffman. Evaluation of a Lu-177 BB2r antagonist in a breast cancer model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4537. doi:10.1158/1538-7445.AM2013-4537