RT Journal Article SR Electronic T1 177Lu-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 FD Society of Nuclear Medicine SP 2017 OP 2024 DO 10.2967/jnumed.109.064444 VO 50 IS 12 A1 Maddalena, Mary Ellen A1 Fox, Jaclyn A1 Chen, Jianqing A1 Feng, Weiwei A1 Cagnolini, Aldo A1 Linder, Karen E. A1 Tweedle, Michael F. A1 Nunn, Adrian D. A1 Lantry, Laura E. YR 2009 UL http://jnm.snmjournals.org/content/50/12/2017.abstract AB 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.