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Using the RIDER technique, i.e., the R5 + 1 approach, changes are introduced to the receptor-ligand cycle by increasing the ligand-receptor binding affinity for a selected target ligand, which allows the choice of a ligand with a higher affinity for the target receptor. This allows the researchers to trace the receptor without being affected by the associated binding affinity, by using a high-affinity ligand in combination with an avid ligand ( 19, 20 ). In addition, the use of R5 + 1 radiotracer technology using the ^68^Ga-DOTA-peptide in NENs is appealing for its high tumor uptake and fast tumor-to-background ratio due to the high positive-to-negative ligand contrast ratio ( 21 ).
The PET/CT examination usually involves the injection of approximately 250-500 MBq 68Ga-DOTATATE i.v. It is recommended to start the PET/CT protocol 45 min after injection, and aim for the maximum feasible 68Ga-DOTATATE accumulation at 30 min post-injection, which helps to minimize the radiation dose. 68Ga-DOTATATE is usually co-administered with 185 MBq 18F-FDG. Detailed patient preparation is very important, but fasting from at least 2 h before 68Ga-DOTATATE injection to the end of the examination is preferable. The circulation time of the tracer is approximately 20 min, although a longer circulation time (up to 40 min) for 68Ga-DOTATATE has been reported (67 ).
For PET/CT imaging, the optimal sequence is a PET/CT immediately followed by a scan of the same field-of-view but with a single-photon emission computed tomography (SPECT) system, which can be performed in 30-60 min. With such protocols, it has been shown that optimal imaging is obtained if 68Ga-DOTATATE is administered prior to a 2-h 18F-FDG injection (43). A dual-tracer protocol can be accomplished by co-injecting 68Ga-DOTATATE and 18F-FDG as early as 1 h after tracer injection. This protocol is an effective means of improving tumor contrast and differentiating tumor from normal tissue. The use of R5 + 1 peptides may extend the dynamic range and sensitivity of a PET ligand by increasing the ratio of specific to non-specific binding ( Fig 6 ). SPECT is an alternative to PET/CT, but this is mostly limited by the large-field-of-view collimation and low resolution. The conventional CT is used to localize the scan, and the SPECT and PET data sets are reconstructed with a single modality using the same iterative method.
Figure 3b. A 69-year-old man with a biopsy-proven grade 2 panNET. (a, b) Axial T1-weighted (a) and contrast-enhanced fat-suppressed T1-weighted (b) MR images show a heterogeneous mildly hyperintense mass (arrows) that is hypervascular at the arterial and early venous phase after injection of contrast material, which is consistent with grade 2 well-differentiated panNET with angioinvasion and lymph node metastasis. (c) Axial 68Ga DOTATATE PET/CT image shows slightly increased uptake in the mass (arrow) compared with the background. Due to the known poor prognosis, surgical resection was recommended.
Figure 6. Graded tumor SSTR expression in a 68-year-old man with neuroendocrine tumor of the pancreas. (a) Coronal 18F-fluorodeoxyglucose PET/CT image shows diffusely increased tracer uptake in the pancreas (arrows) consistent with well-differentiated grade 3 panNET and no evidence of metastatic disease. (b) Coronal 68Ga-DOTATATE PET/CT image shows no evidence of tumor uptake in the pancreas, which suggests a lack of expression of the SSTR2 receptor. The patient was confirmed to have a grade 3 well-differentiated panNET by EUS-guided biopsy.
Figure 7. Graded tumor SSTR expression in a 30-year-old woman with well-differentiated panNEC. (a) Coronal 18F-fluorodeoxyglucose PET/CT image shows increased tracer uptake in the splenic mass (arrow) (SUVmax = 10.1). (b) Coronal 68Ga-DOTATATE PET/CT image shows no evidence of tumor uptake in the splenic mass, which suggests a lack of expression of the SSTR2 receptor.
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