Institute of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937, Cologne, Germany.
Department of Nuclear Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937, Cologne, Germany.
BMC Cancer. 2019 Jun 26;19(1):633. doi: 10.1186/s12885-019-5841-8.
The recent implementation of PET with prostate specific membrane antigen (PSMA)-specific radiotracers into the clinical practice has resulted in the significant improvement of accuracy in the detection of prostate carcinoma (PCa). PSMA-expression in ganglia has been regarded as an important pitfall in prostate carcinoma-PET diagnostics but has not found any practical use for diagnosis or therapy.
We explored this phenomenon and demonstrated the applicability of peripheral ganglia in healthy rats as surrogates for small PSMA positive lesions for the preclinical evaluation of diagnostic PCa PET probes. Healthy rats were measured with PET/CT using the tracers [F]DCFPyL, [AlF]PSMA-11 and [Ga]PSMA-11. Sections of ganglia were stained with an anti-PSMA antibody. [F]DCFPyL uptake in ganglia was compared to that in LNCaP tumor xenografts in mice.
Whereas [F]DCFPyL and [Ga]PSMA-11 were stable in vivo and accumulated in peripheral ganglia, [AlF]PSMA-11 suffered from fast in vivo deflourination resulting in high bone uptake. Ganglionic PSMA expression was confirmed by immunohistochemistry. [F]DCFPyL uptake and signal-to-noise ratio in the superior cervical ganglion was not significantly different from LNCaP xenografts.
Our results demonstrated the non-inferiority of the novel model compared to conventionally used tumor xenografts in immune compromised rodents with regard to reproducibility and stability of the PSMA signal. Furthermore, the model involves less expense and efforts while it is permanently available and avoids tumor-growth associated animal morbidity and distress. To the best of our knowledge, this is the first tumor-free model suitable for the in vivo evaluation of tumor imaging agents.
最近，前列腺特异性膜抗原（PSMA）特异性放射性示踪剂的 PET 已在临床实践中得到应用，这显著提高了前列腺癌（PCa）检测的准确性。神经节中的 PSMA 表达被认为是前列腺癌 PET 诊断中的一个重要陷阱，但尚未发现其在诊断或治疗中有任何实际用途。
我们探讨了这一现象，并证明了健康大鼠周围神经节作为小 PSMA 阳性病变的替代物在诊断 PCa PET 探针的临床前评估中的适用性。使用示踪剂 [F]DCFPyL、[AlF]PSMA-11 和 [Ga]PSMA-11 对健康大鼠进行 PET/CT 测量。用抗 PSMA 抗体对神经节进行染色。比较了 [F]DCFPyL 在神经节中的摄取与小鼠 LNCaP 肿瘤异种移植中的摄取。
尽管 [F]DCFPyL 和 [Ga]PSMA-11 在体内稳定且在周围神经节中积累，但 [AlF]PSMA-11 体内脱氟速度很快，导致骨摄取增加。免疫组织化学证实了神经节中的 PSMA 表达。颈上神经节中 [F]DCFPyL 的摄取和信噪比与 LNCaP 异种移植无显著差异。
我们的结果表明，与免疫功能低下的啮齿动物中常用的肿瘤异种移植相比，该新型模型在 PSMA 信号的重现性和稳定性方面具有非劣效性。此外，该模型还涉及更少的费用和努力，而且它是永久性的，可避免与肿瘤生长相关的动物发病和痛苦。据我们所知，这是第一个适用于肿瘤成像剂体内评估的无肿瘤模型。
