American Association for Cancer Research
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Supplemental Figures 1 - 6, Table 1 from Applications of ImmunoPET: Using 124I-Anti-PSCA A11 Minibody for Imaging Disease Progression and Response to Therapy in Mouse Xenograft Models of Prostate Cancer

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journal contribution
posted on 2023-03-31, 18:49 authored by Scott M. Knowles, Richard Tavaré, Kirstin A. Zettlitz, Matthew M. Rochefort, Felix B. Salazar, Ziyue Karen Jiang, Robert E. Reiter, Anna M. Wu

Supplemental Figure 1: Transfection of 22rv1 with FLuc-IRES-mCherry and 22rv1_PSCA with Fluc-IRES-GFP and FACS sorting created FLuc expressing PSCA positive and negative cell lines. Supplemental Figure 2: H&E Staining of 22rv1 and 22rv1_PSCA intratibial xenografts shows mixed osteolytic (blue dashed arrows) and osteoblastic (solid red arrows) type tumor formation. Supplemental Figure 3: Comparison of optical imaging, 18F-Fluoride Bone Scan, and A11 immunoPET in mice bearing 22rv1 intratibial xenograft 6 weeks post-xenograftimplantation. Supplemental Figure 4: Comparison of optical imaging, 18F-Fluoride Bone Scan, and A11 immunoPET in a mouse bearing a 22rv1_PSCA intratibial xenograft at 2 and 6 weeks postxenograft- implantation. Supplemental Figure 5: Quantification of tumor necrosis using ImageJ based color Segmentation. Supplemental Figure 6: H&E staining of LAPC-9 tumors treated with either MDV-3100 or vehicle control. Supplemental Table 1: 44 hour biodistribution of mice bearing 22rv1 and 22rv1_PSCA intratibial xenografts. Histologic analysis of control and MDV-3100 treated tumors.



Purpose: Prostate stem cell antigen (PSCA) is highly expressed in local prostate cancers and prostate cancer bone metastases and its expression correlates with androgen receptor activation and a poor prognosis. In this study, we investigate the potential clinical applications of immunoPET with the anti-PSCA A11 minibody, an antibody fragment optimized for use as an imaging agent. We compare A11 minibody immunoPET to 18F-Fluoride PET bone scans for detecting prostate cancer bone tumors and evaluate the ability of the A11 minibody to image tumor response to androgen deprivation.Experimental Design: Osteoblastic, PSCA-expressing, LAPC-9 intratibial xenografts were imaged with serial 124I-anti-PSCA A11 minibody immunoPET and 18F-Fluoride bone scans. Mice bearing LAPC-9 subcutaneous xenografts were treated with either vehicle or MDV-3100 and imaged with A11 minibody immunoPET/CT scans pre- and posttreatment. Ex vivo flow cytometry measured the change in PSCA expression in response to androgen deprivation.Results: A11 minibody demonstrated improved sensitivity and specificity over 18F-Fluoride bone scans for detecting LAPC-9 intratibial xenografts at all time points. LAPC-9 subcutaneous xenografts showed downregulation of PSCA when treated with MDV-3100 which A11 minibody immunoPET was able to detect in vivo.Conclusions: A11 minibody immunoPET has the potential to improve the sensitivity and specificity of clinical prostate cancer metastasis detection over bone scans, which are the current clinical standard-of-care. A11 minibody immunoPET additionally has the potential to image the activity of the androgen signaling axis in vivo which may help evaluate the clinical response to androgen deprivation and the development of castration resistance. Clin Cancer Res; 20(24); 6367–78. ©2014 AACR.