Radiolabeled somatostatin analogues for the diagnosis and therapy of NETs: upcoming new strategies

Octreotide is the progenitor of the somatostatin analogues (SSA) family, which includes radiopharmaceuticals suitable for SPECT, PET and radionuclide therapy, within an effective theragnostic model. Nowadays, PET/CT performed using DOTA peptides radiolabeled with Gallium-68 is considered the best molecular imaging procedure in staging and restaging of neuroendocrine tumors (NETs), while new SSA are being successfully developed for Peptide Receptor Radionuclide Therapy (PRRT). Technological developments both in the area of PET and MRI are likely to open new avenues for the optimization of the diagnostic workup of NETs. The aim of this paper is to present an up-to-date overview of the role of diagnostic 68Ga-SSA/PET hybrid imaging with MRI or CT, for the workup of NETs, as well as the perspectives arising from the use of therapeutic SSA radiopharmaceuticals either alone or in combination with cold SSA. A literature review of the most relevant papers in the field of radiolabeled SSA used for diagnosis or therapy demonstrates that PET/MRI as compared to PET/CT has a slightly higher diagnostic accuracy in detecting liver metastases but a lower accuracy in detecting pulmonary secondary lesions. In the present scenario, PET/CT remains the most cost-effective choice, integrated with an abdominal MRI when needed. Concurrently with the growth of PRRT performed with Lutetium-177 or Yttrium-90 DOTA peptides, new strategies to improve the therapeutic outcome are being sought with combined treatments using radioactively labeled SSA along with cold SSA. Interesting perspectives are opened by the availability of PET/MRI and full digital PET/CT due to the improved detector sensitivity and spatial resolution. At the same time, new strategies will be sought based on the association of PRRT with old and/or newer oncologic therapeutic strategies, or on the use of radionuclide cocktails. An intriguing future can be envisaged due to the commercial availability of radiopharmaceuticals labeled with alpha emitting radionuclides, which may allow better results compared to beta-emitters, likely due to the bystander and/or abscopal effect.