Renal and Red Marrow Dosimetry in Peptide Receptor Radionuclide Therapy: 20 Years of History and Ahead

The development of dosimetry and studies in peptide receptor radionuclide therapy (PRRT) over the past two decades are reviewed. Differences in kidney and bone marrow toxicity reported between Y-90, Lu-177 and external beam radiotherapy (EBRT) are discussed with regard to the physical properties of these beta emitter radionuclides. The impact of these properties on the response to small and large tumors is also considered. Capacities of the imaging modalities to assess the dosimetry to target tissues are evaluated. Studies published in the past two years that confirm a red marrow uptake in Lu-177-DOTATATE therapy, as already observed 20 years ago in Y-86-DOTATOC PET studies, are analyzed in light of the recent developments in the transferrin transport mechanism. The review enlightens the importance (i) of using state-of-the-art imaging modalities, (ii) of individualizing the activity to be injected with regard to the huge tissue uptake variability observed between patients, (iii) of challenging the currently used but inappropriate blood-based red marrow dosimetry and (iv) of considering individual tandem therapy. Last, a smart individually optimized tandem therapy taking benefit of the bi-orthogonal toxicity-response pattern of Lu-177-DOTATATE and of Y-90-DOTATOC is proposed.