Research process of PET tracers for neuroendocrine tumors diagnosis

Neuroendocrine tumors (NETs) can affect several organ systems and present a variety of clinical symptoms, which are difficult to diagnose by conventional methods. Somatostatin receptor (SSTR) is a group of specific receptors expressed on the well-differentiated NET cell membrane. [⁶⁸Ga]-labeled somatostatin analogues (SSAs) PET/CT, endogenous ligands targeting SSTR, is widely used in currently clinical NETs diagnosis. The dual-tracer strategy ([⁶⁸Ga]Ga-SSAs + [¹⁸F]FDG) allows for a more detailed evaluation of tumor metabolism and receptor expression. The NETPET score, integrating [⁶⁸Ga]Ga-SSAs PET/CT and [¹⁸F]FDG PET/CT results, enhances the accuracy of predicting treatment response and prognosis. In addition, novel isotopes ([¹⁸F]/[⁶⁴Cu]) labeled SSAs and SSTR antagonists outperformed [⁶⁸Ga]-SSAs in lesion detection, tumor uptake, and tumor-to-background ratio. Due to undifferentiated or dedifferentiated NETs, SSTR may not be expressed. [⁶⁸Ga]Ga-Pentixafor and [¹⁸F]-FDG PET/CT are applicable for SSTR-negative NET diagnosis. [¹⁸F]-MFBG and [¹⁸F]-DOPA have a higher sensitivity for identifying non-metastatic pheochromocytoma and paraganglioma (PPGL) than other radiotracers. This review addressed NET diagnosis with conventional imaging techniques, the clinical application of novel radiotracers, and the merits and limitations of the various radiotracers.