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 these two last decades are reviewed. Differences in kidney and bone marrow toxicity reported between 90Y, 177Lu and external beam radiotherapy (EBRT) are discussed with regards 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 last two years that confirm a red marrow uptake in 177Lu-DOTATATE therapy, as already observed 20 years ago in 86Y-DOTATOC PET studies, are commented and analyzed in the light of the recent knowledges in 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 regards 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 individually tandem therapy. Last, a smart individually optimized tandem therapy taking benefit of the bi-orthogonal toxicity-response pattern of 177Lu-DOTATATE and of 90Y-DOTATOC is proposed.