Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors

Peptide receptor radionuclide therapy (PRRT), over the years, has evolved as an important modality in the therapeutic armamentarium of advanced, metastatic or inoperable, progressive Neuroendocrine Neoplasms (NENs). This review deliberates on the basic understanding and applied clinical aspects of PRRT in NENs, with special reference to (1) tumor biology and receptor characteristics, (2) molecular PET-CT imaging (in particular the invaluable role of dual-tracer PET with [⁶⁸Ga]-DOTA-TATE/NOC and [¹⁸F]-FDG for exploring tumor biology in continuum and individualizing treatment decision making) and NEN theranostics, (3) relevant radiochemistry of different therapeutic radionuclides (both beta emitting ¹⁷⁷Lu-DOTATATE and ⁹⁰Y-DOTATATE and alpha emitting ²²⁵Ac-DOTATATE), and (4) related dosimetric considerations. Successful clinical management of the NENs would require multifactorial considerations, and all the aforementioned points pertaining to the disease process and available logistics are key considerations for state-of-the-art clinical practice and delivering personalized care in this group of patients. Emphasis has been placed on relatively intriguing areas such as (1) NET grade 3 of WHO 2017 classification (ie, Ki-67>20% but well-differentiation features), (2) "Neoadjuvant PRRT," (3) combining chemotherapy and PRRT, (4) 'Sandwich Chemo-PRRT', (5) duo-PRRT and tandem PRRT, (6) resistant functioning disease with nuances in clinical management and how one can advocate PRRT rationally in such clinical settings and individualize the management in a patient specific manner. Relevant clinical management issues related to some difficult case scenarios, which the Nuclear Medicine attending physician should be aware of to run an efficient clinical PRRT services, are described.