*3.4. Cholecystokinin-2 Receptor (CCK2R)-Targeting Probes*

CCK2R is highly expressed in 90% of MTC, 50% of small cell lung cancers, 60% of astrocytomas, insulinomas, stromal ovarian cancers, gastrointestinal stromal tumors, and more than 20% of gastroenteropancreatic tumors [93–95]. As a new peptide tracer targeting CCK2R, 68Ga-DOTA-MGS5 is supposed to be superior to [18F]FDOPA in diagnosing MTCs. The comparison between the [68Ga]Ga-DOTA-MGS5 and [18F]FDOPA was performed in a 75-year-old female patient with recurrent MTC (calcitonin: 2726 ng/l), who underwent consecutive [68Ga]Ga-DOTA-MGS5 and [18F]FDOPA-PET/CT. [68Ga]Ga-DOTA-MGS5 found three obvious liver lesions with higher uptake than [18F]FDOPA-PET/CT (SUVmax = 6.4–8.3 vs. 3.7) and showed a good lesion-to-background contrast in the liver, which might yield complementary information to [18F]FDOPA-PET in patients with recurrent MTC [96] (Figure 7). The background of [68Ga]Ga-DOTA-MGS5 seems higher than that of [18F]FDOPA in our opinion.

**Figure 5.** PET/CT imaging comparing [68Ga]Ga-DOTA-RGD2 and [18F]FDG. The RR-DTC case showed a high level of stimulated Tg (85 ng/mL) and negative 131I post-therapy whole-body scan. Histopathology confirmed the metastatic lesions. (**A**) A maximum intensity projection (MIP) image showed [68Ga]Ga-DOTA-RGD2 positive foci in the lower cervical region. (**B**) The corresponding MIP image of [18F]FDG. (**C**) Fused PET/CT showed the metastatic foci was [68Ga]Ga-DOTA-RGD2 positive; (**D**) the corresponding foci is negative on [18F]FDG fused PET/CT. Reproduced with permission from [85], copyright 2020 Mary Ann Liebert Inc.

**Figure 6.** (**A**,**C**) PET and PET/CT fusion images showed slight [68Ga]Ga-PSMA uptake in the thyroid nodule of a 62-year-old patient with prostate cancer. The thyroid nodule was validated as Hürthle cell angioinvasive FTC by post-thyroidectomy pathology. Reproduced with permission from [88] copyright 2016 Society of Nuclear Medicine and Molecular Imaging. (**B**,**D**) PET and PET/CT fusion image marked 68Ga-PSMA uptake in the thyroid nodule of a 65-year-old man with metastatic prostate cancer. The thyroid nodule was regarded as TC proved by post-thyroidectomy pathology. Reproduced with permission from [91], copyright 2017 Wolters Kluwer Health Inc.

**Figure 7.** Comparison of [18F]FDOPA and [68Ga]Ga-DOTA-MGS5 in MTC patients. (**A**) [18F]FDOPA PET imaging at one hour post-injection. (**B**) 68Ga-Ga-DOTA-MGS5 PET imaging at one-hour post-injection. [68Ga]Ga-DOTA-MGS5 yields complementary information to [18F]FDOPA-PET. Reproduced with permission from [96], copyright 2021, Springer Nature Inc.
