Chevalier Simone, Moffett Serge, Turcotte Eric, Luz Murillo, Chauvette Lyne, Derbekyan Vilma, Scarlata Eleonora, Zouanat Fatima, Aprikian Armen G, Anidjar Maurice
Urologic Oncology Research Group, Division of Urology, Department of Surgery, McGill University, and Research Institute (RI) of McGill University Health Centre (MUHC), 1001 Boulevard Décarie, Montréal, QC, H4A 3J1, Canada.
ProScan, Rx Pharma Inc., 5800 Royalmount Avenue, Montréal, QC, H4P 1K5, Canada.
EJNMMI Res. 2015 Dec;5(1):77. doi: 10.1186/s13550-015-0155-6. Epub 2015 Dec 30.
Clinical applicability of newly discovered reagents for molecular imaging is hampered by the lack of translational models. As the dog prostate cancer (DPC-1) model recapitulates in dogs the natural history of prostate cancer in man, we tested the feasibility of single-photon emission computed tomography (SPECT)/CT imaging in this model using an anti-prostate-specific membrane antigen (PSMA)/17G1 antibody as the radiotracer.
Immunoblots and immunohistochemistry (IHC) with 17G1 were performed on canine and human prostate cancer cell lines and tissues. Five dogs with DPC-1 tumors were enrolled for pelvic and, in some instances, thoracic SPECT/CT procedures, also repeated over time. Controls included (111)indium (In)-17G1 prior to DPC-1 implantation and (111)In-immunoglobulins (IgGs) prior to imaging with (111)In-17G1 in dogs bearing prostatic DPC-1 tumors.
17G1 cross-reactivity with canine PSMA (and J591) was confirmed by protein analyses on DPC-1, LNCaP, and PC-3 cell lines and IHC of dog vs. human prostate tissue sections. 17G1 stained luminal cells and DPC-1 cancer cells in dog prostates similarly to human luminal and cancer cells of patients and LNCaP xenografts. SPECT/CT imaging revealed low uptake (≤2.1) of both (111)In-17G1 in normal dog prostates and (111)In-IgGs in growing DPC-1 prostate tumors comparatively to (111)In-17G1 uptake of 3.6 increasing up to 6.5 values in prostate with DPC-1 lesions. Images showed a diffused pattern and, occasionally, a peripheral doughnut-shape-like pattern. Numerous sacro-iliac lymph nodes and lung lesions were detected with contrast ratios of 5.2 and 3.0, respectively. The highest values were observed in pelvic bones (11 and 19) of two dogs, next confirmed as PSMA-positive metastases.
This proof-of-concept PSMA-based SPECT/CT molecular imaging detecting primary prostate tumors and metastases in canines with high cancer burden speaks in favor of this large model's utility to facilitate technology transfer to the clinic and accelerate applications of new tools and modalities for tumor staging in patients.
新发现的分子成像试剂的临床应用因缺乏转化模型而受到阻碍。由于犬前列腺癌（DPC-1）模型在犬类中重现了人类前列腺癌的自然病史，我们使用抗前列腺特异性膜抗原（PSMA）/17G1抗体作为放射性示踪剂，测试了该模型中单光子发射计算机断层扫描（SPECT）/CT成像的可行性。
用17G1对犬和人前列腺癌细胞系及组织进行免疫印迹和免疫组织化学（IHC）检测。5只患有DPC-1肿瘤的犬被纳入盆腔检查，在某些情况下还进行胸部SPECT/CT检查，并且随着时间推移重复进行。对照组包括DPC-1植入前的（111）铟（In）-17G1以及患有前列腺DPC-1肿瘤的犬在用（111）In-17G1成像前的（111）In-免疫球蛋白（IgG）。
通过对DPC-1、LNCaP和PC-3细胞系的蛋白质分析以及犬与人前列腺组织切片的IHC检测，证实了17G1与犬PSMA（和J591）的交叉反应性。17G1对犬前列腺中的管腔细胞和DPC-1癌细胞的染色与患者的人管腔细胞和癌细胞以及LNCaP异种移植物相似。SPECT/CT成像显示正常犬前列腺中（111）In-17G1和生长中的DPC-1前列腺肿瘤中（111）In-IgG的摄取率较低（≤2.1），而在有DPC-1病变的前列腺中，（111）In-17G1的摄取率从3.6增加到6.5。图像显示为弥漫性模式，偶尔为外周甜甜圈状模式。检测到许多骶髂淋巴结和肺部病变，对比率分别为5.2和3.0。在两只犬的骨盆骨中观察到最高值（11和19），随后证实为PSMA阳性转移灶。
这种基于PSMA的SPECT/CT分子成像概念验证能够检测高癌症负荷犬的原发性前列腺肿瘤和转移灶，这表明该大型模型有助于促进技术向临床转化，并加速新工具和方法在患者肿瘤分期中的应用。
