TY - JOUR T1 - <sup>177</sup>Lu-AMBA Biodistribution, Radiotherapeutic Efficacy, Imaging, and Autoradiography in Prostate Cancer Models with Low GRP-R Expression JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 2017 LP - 2024 DO - 10.2967/jnumed.109.064444 VL - 50 IS - 12 AU - Mary Ellen Maddalena AU - Jaclyn Fox AU - Jianqing Chen AU - Weiwei Feng AU - Aldo Cagnolini AU - Karen E. Linder AU - Michael F. Tweedle AU - Adrian D. Nunn AU - Laura E. Lantry Y1 - 2009/12/01 UR - http://jnm.snmjournals.org/content/50/12/2017.abstract N2 - 177Lu-DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2 (177Lu-AMBA) is a radiolabeled bombesin derivative that is bound and internalized by cells expressing the G-protein–coupled gastrin-releasing peptide receptor (GRP-R) and is currently in phase I clinical trials. In previous radiotherapy studies with PC-3 xenografted mice, 177Lu-AMBA treatment significantly increased survival and reduced tumor growth rates. The PC-3 tumor cell line has an elevated expression of GRP-Rs (2.5 × 105/cell), whereas LNCaP—a prostate cancer metastatic cell line representing the early androgen-sensitive stage of prostate cancer—and DU145—an androgen-insensitive metastatic line—express lower receptor numbers (5.9 × 103 and 1.2 × 104/cell, respectively). Because of tumor heterogeneity, the high number of receptors in the PC-3 line may not represent the clinical situation, and little definitive work on the GRP-R status of primary prostate tumors and metastases exists. We sought to evaluate the tumor binding and imaging potential of 177Lu-AMBA in low GRP-R models of prostate cancer and determine how reduced expression affects 177Lu-AMBA radiotherapy efficacy. Methods: The LNCaP and DU145 cell lines were used to determine the binding (Kd), retention, and efflux of 177Lu-AMBA. Biodistribution radiotherapy, imaging, and autoradiography studies were performed in LNCaP, DU145, or PC-3 tumor–bearing male nude mice. Immunohistochemistry was used to determine the proliferative state in LNCaP and DU145 models and the vascular phenotype of LNCaP radiotherapy tumors. Results: 177Lu-AMBA binds to GRP-R in these cell lines with high affinity (Kd of LNCaP, 0.65 ± 0.2 nM; Kd of DU145, 0.53 ± 0.1 nM). The uptake of 177Lu-AMBA is at least 10-fold less in LNCaP and DU145 cell lines than it is in the PC-3 cell line. Autoradiography identifies activity concentrated in areas of viable tumor tissue, and γ-images of 177Lu-AMBA identify tumors in vivo. Despite having lower uptake, 177Lu-AMBA demonstrated radiotherapeutic efficacy and decreased proliferation in the LNCaP and DU145 xenografts; in the LNCaP model, 177Lu-AMBA normalized the phenotype of microvasculature, reducing tumoral blood pooling. Conclusion: 177Lu-AMBA is a single radiolabeled agent that combines targeted radiotherapy after imaging dosimetry with the potential for single-agent or multimodality therapy for prostate cancer. ER -