背景：放射治疗学的概念依赖于恶性细胞上生物分子靶标的过度表达，以将诊断/治疗放射性核素载体特异性地定向到癌症病变。可以巧妙地利用病理病变中多个靶标的伴随表达来提高诊断灵敏度和治疗效果。为了实现这一目标，我们探索了[99mTc]Tc-DT11（DT11，N4-Lys（MPBA-PEG4）-Arg-Arg-Pro-Tyr-Ile-Leu-OH；NTS1R特异性）组合应用的第一个例子前列腺癌模型中的 [99mTc]Tc-DB7（DB7，N4-PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt；GRPR 特异性）。方法：因此，将 [99mTc]Tc-DT11 的行为与 [99mTc]Tc-DT11 [99mTc]Tc-DB7 混合物在前列腺腺癌 PC-3 细胞和小鼠异种移植物中的行为进行比较。还研究了 Entresto®（作为强效脑啡肽酶抑制剂 sacubitrilat 的来源）稳定两种放射性示踪剂的影响。结果：[99mTc]Tc-DT11 [99mTc]Tc-DB7 混合物的 PC-3 细胞结合超过 [99mTc]Tc-DT11。同样，注射后 4 小时，PC-3 肿瘤对 [99mTc]Tc-DT11 [99mTc]Tc-DB7 混合物的摄取优于 [99mTc]Tc-DT11 (4.23) (7.70 ± 0.89%IA/g)。 ± 0.58%IA/g；p < 0.0001)。 Entresto® 治疗导致肿瘤摄取进一步增强（达到 11.57 ± 1.92%IA/g；p < 0.0001）。结论：总而言之，这项针对前列腺癌模型的首次临床前研究揭示了 NTS1R/GRPR 双重靶向的明显优势，证明了在其他癌症模型中进一步评估这一有前途的概念的合理性。

Background: The concept of radiotheranostics relies on the overexpression of a biomolecular target on malignant cells to direct diagnostic/therapeutic radionuclide-carriers specifically to cancer lesions. The concomitant expression of more than one target in pathological lesions may be elegantly exploited to improve diagnostic sensitivity and therapeutic efficacy. Toward this goal, we explored a first example of a combined application of [99mTc]Tc-DT11 (DT11, N4-Lys(MPBA-PEG4)-Arg-Arg-Pro-Tyr-Ile-Leu-OH; NTS1R-specific) and [99mTc]Tc-DB7(DB7, N4-PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; GRPR-specific) in prostate cancer models. Methods: Accordingly, the behavior of [99mTc]Tc-DT11 was compared with that of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture in prostate adenocarcinoma PC-3 cells and xenografts in mice. The impact of stabilizing both radiotracers by Entresto®, as a source of the potent neprilysin inhibitor sacubitrilat, was also investigated. Results: The PC-3 cell binding of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture surpassed that of [99mTc]Tc-DT11. Likewise, the PC-3 tumor uptake of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture at 4 h post-injection was superior (7.70 ± 0.89%IA/g) compared with [99mTc]Tc-DT11 (4.23 ± 0.58%IA/g; p < 0.0001). Treatment with Entresto® led to further enhancement of the tumor uptake (to 11.57 ± 1.92%IA/g; p < 0.0001). Conclusions: In conclusion, this first preclinical study on prostate cancer models revealed clear advantages of dual NTS1R/GRPR targeting, justifying further assessment of this promising concept in other cancer models.