Molecular Imaging and Therapy Service (Nuclear Medicine), Fiona Stanley Hospital, Perth, Australia.
Molecular Imaging and Therapy Service (Nuclear Medicine), Royal Perth Hospital, Perth, Australia.
Eur J Nucl Med Mol Imaging. 2017 Aug;44(9):1455-1462. doi: 10.1007/s00259-017-3699-z. Epub 2017 May 4.
Gallium(68)-labelled prostate-specific membrane antigen (PSMA) radiopharmaceuticals can be used to detect prostate cancer (PCa) cells due the their over expression of PSMA. The Ga HBED-PSMA (PSMA-HBED) ligand has been most widely used and can be considered the current gold standard agent. Further PSMA ligands based on the DOTAGA and DOTA conjugates have more recently been developed. These agents (PSMA-I&T and PSMA-617) have potential theranostic capabilities as they can be conjugated with therapeutic radioisotopes. In this study, we examine whether PSMA-I&T has comparative efficacy, such that it could replace PSMA-HBED as a diagnostic agent in prostate carcinoma.
19 patients with PCa referred for Ga-PSMA imaging were imaged with PSMA-HBED and PSMA-I&T PET-CT imaging within a 2-week period. The two pharmaceuticals were synthesised using click chemistry. Imaging was performed using the same standardised methodology on a Siemens Biograph mCT. All sites of PSMA binding thought to represent PCa (probable or definite) were included in a lesion analysis that examined lesion concordance and lesional binding efficiency (SUV) between the two radiopharmaceuticals. For each patient, SUV of the LV cavity blood pool, bone, muscle and liver were determined as image background measures.
Across all patients, PSMA uptake was observed in 47 lesions (10 bone lesions, 19 nodal lesions, 18 high-grade intraprostatic binding). Lesions were concordant between the agents in all except for two small (<4 mm) nodal lesions which were not visualised with PSMA-I&T. SUV assessment showed significantly greater overall lesion binding with HBED (paired t test, p = 0.0001). LV blood pool and bone marrow SUV were significantly higher for I&T than HBED (paired t test, blood pool p < 1 × 10-5, bone marrow p < 0.005).
Intra-patient comparative imaging demonstrates higher lesional PSMA-HBED binding than PSMA-I&T and that the HBED agent is likely to have better lesion contrast. While there was concordance in 96% of lesions, 2 small nodal lesions were appreciated with PSMA-HBED imaging while considered normal with PSMA-I&T. These findings suggest that HBED-PSMA has a slightly higher diagnostic accuracy in comparison to PSMA-I&T.
由于前列腺特异性膜抗原（PSMA）的过度表达，镓（68）标记的前列腺特异性膜抗原（PSMA）放射性药物可用于检测前列腺癌（PCa）细胞。Ga HBED-PSMA（PSMA-HBED）配体应用最为广泛，可被视为当前的金标准药物。最近，又开发了基于 DOTAGA 和 DOTA 缀合物的进一步 PSMA 配体。这些药物（PSMA-I&T 和 PSMA-617）具有潜在的治疗诊断能力，因为它们可以与治疗性放射性同位素结合。在这项研究中，我们研究了 PSMA-I&T 是否具有相似的疗效，以便可以替代 PSMA-HBED 作为前列腺癌的诊断剂。
在 2 周内，对 19 名患有 PCa 的患者进行了 Ga-PSMA 成像，使用 PSMA-HBED 和 PSMA-I&T PET-CT 成像进行了成像。两种药物均通过点击化学合成。使用相同的标准化方法在西门子 Biograph mCT 上进行了成像。所有被认为代表前列腺癌（可能或确定）的 PSMA 结合部位均包含在病变分析中，该分析检查了两种放射性药物之间的病变一致性和病变结合效率（SUV）。对于每位患者，确定了 LV 腔血池、骨骼、肌肉和肝脏的 SUV 作为图像背景测量值。
在所有患者中，均在 47 个病变中观察到 PSMA 摄取（10 个骨病变，19 个淋巴结病变，18 个高分级前列腺内结合病变）。除了两个较小的（<4mm）淋巴结病变无法用 PSMA-I&T 显示外，两种药物在所有病变中均具有一致性。SUV 评估显示 HBED 总体病变结合度明显更高（配对 t 检验，p=0.0001）。与 HBED 相比，I&T 的 LV 血池和骨髓 SUV 均明显更高（配对 t 检验，血池 p<1×10-5，骨髓 p<0.005）。
在患者内进行的比较成像显示，PSMA-HBED 结合的病变比 PSMA-I&T 更高，并且 HBED 试剂可能具有更好的病变对比度。尽管 96％的病变具有一致性，但在 PSMA-HBED 成像中可以发现 2 个较小的淋巴结病变，而在 PSMA-I&T 中则被认为是正常的。这些发现表明，与 PSMA-I&T 相比，HBED-PSMA 在诊断准确性方面略有提高。
