Patient-specific dosimetry in peptide receptor radionuclide therapy: a clinical review

Abstract

Neuroendocrine tumours (NETs) belong to a relatively rare class of neoplasms. Nonetheless, their prevalence has increased significantly during the last decades. Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment approach for inoperable or metastasised NETs. The therapeutic effect is based on the binding of radiolabelled somatostatin analogue peptides with NETs' somatostatin receptors, resulting in internal irradiation of tumours. Pre-therapeutic patient-specific dosimetry is essential to ensure that a treatment course has high levels of safety and efficacy. This paper reviews the methods applied for PRRT dosimetry, as well as the dosimetric results presented in the literature. Focus is given on data concerning the therapeutic somatostatin analogue radiopeptides (111)In-[DTPA(0),D-Phe(1)]-octreotide ((111)In-DTPA-octreotide), (90)Y-[DOTA(0),Tyr(3)]-octreotide ((90)Y-DOTATOC) and (177)Lu-[DOTA(0),Tyr(3),Thr(8)]-octreotide ((177)Lu-DOTATATE). Following the Medical Internal Radiation Dose (MIRD) Committee formalism, dosimetric analysis demonstrates large interpatient variability in tumour and organ uptake, with kidneys and bone marrow being the critical organs. The results are dependent on the image acquisition and processing protocol, as well as the dosimetric imaging radiopharmaceutical.

Side Effects of CXC-Chemokine Receptor 4–Directed Endoradiotherapy with Pentixather Before Hematopoietic Stem Cell Transplantation

“…The effective half-life of the dominant component was 37 6 12 h with 1 outlier at 97 h, which is slightly shorter than typically observed in octreotide endoradiotherapy (19)(20)(21). The renal absorbed dose per unit administered activity was 1.6 6 0.7 Gy/GBq 177 Lu-pentixather without nephroprotection, which is slightly higher than in octreotide endoradiotherapy (22). The nephroprotective medication reduced the therapeutic maximum kidney dose per administered activity in the 6 patients treated with 177 Lu-pentixather to 64% 6 13% of the values measured in pretherapeutic dosimetry.…”

Parametric Net Influx Rate Images of 68Ga-DOTATOC and 68Ga-DOTATATE: Quantitative Accuracy and Improved Image Contrast

“…During the last decade, peptide receptor radionuclide therapy (PRRT), with radiolabeled SSAs such as 177 Lu-DOTATATE and 90 Y-DOTATOC, has been shown to be effective and plays an increasingly important role in the treatment of NET patients (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). However, large interpatient variability in organ distribution and consequently radiation dose delivered to the lesions and normal organs calls for the development of methods for individualized radiotherapy planning (22). Conventional radiologic imaging techniques such as CT and MRI are well established for the evaluation of therapy response in the clinical routine by assessing changes in tumor size and diagnosing new lesions.…”

90Y-DOTATOC Dosimetry–Based Personalized Peptide Receptor Radionuclide Therapy

“…The 23-Gy threshold that we used for absorbed radiation dose to the kidney comes from established toxicity data from external radiation therapy (21). The dose rate for PRRT is, however, significantly lower than that for external-beam radiation and further decreases over time because of decay of the radiopharmaceutical (13). The lower dose rate for PRRT and the fractionation of treatment allows for DNA repair, potentially reducing tissue damage and increasing the normal-tissue threshold.…”

“…The renal and bone marrow doses, however, can be highly variable among patients. With individual dosimetry, personalized treatment doses can be established to ensure that the total renal dose does not exceed the 23-Gy limit and the bone marrow dose remains below 2 Gy, thresholds generally accepted for radiation toxicity (12,13). For pretherapy dosimetry assessment of 90 Y-DOTATOC, 86 Y-DOTATOC PET/CT may be ideal, but the cost and limited availability of 86 Y limit its routine use.…”