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

Walrand, Stéphan; Jamar, François

doi:10.3390/ijms22158326

Cited by 14 publications

(7 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this setting, our study evaluated the role of simplified methods tested in a series of 30 patients with NEN. The ADs to OARs measured in these patients agreed with previously published data [33][34][35] (Table 8 in Appendix). None of the Table 5 Cumulative AD for VOI obtained with M0, M1, and M2 difference between them and p-values obtained from the Wilcoxon signed rank test for median differences Data are given as mean ± SD (min to max) The renal dose of 23 Gy was not reached, as well as the 28-40 Gy BED [23].…”

Section: Discussionsupporting

confidence: 89%

A comparison of simplified protocols of personalized dosimetry in NEN patients treated by radioligand therapy (RLT) with [177Lu]Lu-DOTATATE to favor its use in clinical practice

Palmese

D'Ambrosio

Gennaro

et al. 2023

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

The role of internal dosimetry is usually proposed for investigational purposes in patients treated by RLT, even if its application is not yet the standard method in clinical practice. This limited use is partially justified by several concomitant factors that make calculations a complex process. Therefore, simplified dosimetry protocols are required. Methods In our study, dosimetric evaluations were performed in thirty patients with NENs who underwent RLT with [177Lu]Lu-DOTATATE. The reference method (M0) calculated the cumulative absorbed dose performing dosimetry after each of the four cycles. Obtained data were employed to assess the feasibility of simplified protocols: defining the dosimetry only after the first cycle (M1) and after the first and last one (M2). Results The mean differences of the cumulative absorbed doses between M1 and M0 were – 10% for kidney, – 5% for spleen, + 34% for liver, + 13% for red marrow, and + 37% for tumor lesions. Conversely, differences lower than ± 10% were measured between M2 and M0. Conclusion Cumulative absorbed doses obtained with the M2 protocol resembled the doses calculated by M0, while the M1 protocol overestimated the absorbed doses in all organs at risk, except for the spleen.

show abstract

Section: Discussionsupporting

confidence: 89%

A comparison of simplified protocols of personalized dosimetry in NEN patients treated by radioligand therapy (RLT) with [177Lu]Lu-DOTATATE to favor its use in clinical practice

Palmese

D'Ambrosio

Gennaro

et al. 2023

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

show abstract

“…Image-based dosimetry has reported threefold or fourfold higher absorbed doses than blood-based methods and established correlations to hematological toxicities [41,42]. This could indicate active bone marrow uptake related to, for example, the transchelation of lutetium-177 onto transferrin, as discussed recently by Walrand et al [43]. Such uptake would likely increase the absorbed dose to cells with transferrin receptor expression as the cells are included in the erythroblastic islands [44].…”

Section: Discussionmentioning

confidence: 94%

Active bone marrow S-values for the low-energy electron emitter terbium-161 compared to S-values for lutetium-177 and yttrium-90

et al. 2022

View full text Add to dashboard Cite

Background Based on theoretical and preclinical results, terbium-161 may be a valid alternative to lutetium-177 and yttrium-90 in radionuclide therapies. The large low-energy electron emission from terbium-161 is a favorable feature in the treatment of disseminated disease, but its impact on the radiosensitive bone marrow needs to be evaluated. Using voxel-based skeletal dosimetry models in which active bone marrow is defined as regions containing stem cells and progenitor cells of the hematopoietic lineage, we generated S-values (absorbed dose per decay) for terbium-161 and evaluated its distribution-dependence in bone marrow cavities. Methods S-values in the active bone marrow were calculated for terbium-161, lutetium-177, and yttrium-90 irradiation using two (male/female) image-based bone marrow dosimetry models. The radionuclides were distributed to one of the three structures that define the spongiosa bone region in the skeletal models: (i) active bone marrow, (ii) inactive bone marrow, or (iii) surface or whole volume of the trabecular bone. Decay data from ICRP 107 were combined with specific absorbed fractions to calculate S-values for 13 skeletal sites. To increase the utility, the skeletal site-specific S-values were averaged to produce whole-body average S-values and spongiosa average S-values. Results For yttrium-90, the high-energy β particles irradiate the active marrow regardless of the source compartment, consistently generating the highest S-values (65–90% higher). Between terbium-161 and lutetium-177, the largest differences in S-values were with an active marrow source (50%), such as self-irradiation, due to the contribution of the short-ranged conversion and Auger electrons from terbium-161. Their influence decreased as the source moved to inactive marrow or the surface or volume of the trabecular bone, reducing the S-values and the differences between terbium-161 and lutetium-177 (15–35%). Conclusion The S-values of terbium-161 for active bone marrow and, consequently, the bone marrow toxicity profile were more dependent on the radionuclide distribution within the bone marrow cavity than the S-values of lutetium-177 and yttrium-90. This effect was attributed to the considerable low-energy electron emission of terbium-161. Therefore, it will be critical to investigate the bone marrow distribution of a particular radiopharmaceutical for accurate estimation of the active bone marrow dose.

show abstract

“…This enhanced effect of combining rA1M and Vamin might be the result of amino acids reducing the renal uptake of 177 Lu-DOTATATE by ~50% by competing with the megalin/cubilin complex. Although this otherwise results in retainment of the radiopeptides in the renal interstitium [38], rA1Ms co-localization with 177 Lu-DOTATATE most probably reduces the resulting oxidative cascade from the radiation. Interestingly, no protective effect was seen on bone marrow cellularity or circulating peripheral blood reticulocytes with Vamin alone; instead, the addition of Vamin seemed to reduce the effect of rA1M.…”

Section: Discussionmentioning

confidence: 99%

Recombinant α1-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a 177Lu-DOTATATE Mouse Radiation Model

et al. 2023

View full text Add to dashboard Cite

177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although 177Lu-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associated with nausea and vomiting in patients. α1-microglobulin (A1M) is an antioxidant with heme- and radical-scavenging abilities. A recombinant form (rA1M) has previously been shown to be renoprotective in preclinical models, including in PRRT-induced kidney damage. Here, we further investigated rA1M’s renal protective effect in a mouse 177Lu-DOTATATE model in terms of administration route and dosing regimen and as a combined therapy with amino acids (Vamin). Moreover, we investigated the protective effect of rA1M on peripheral blood and bone marrow cells, as well as circulatory biomarkers. Intravenous (i.v.) administration of rA1M reduced albuminuria levels and circulatory levels of the oxidative stress-related protein fibroblast growth factor-21 (FGF-21). Dual injections of rA1M (i.e., at 0 and 24 h post-177Lu-DOTATATE administration) preserved bone marrow cellularity and peripheral blood reticulocytes. Administration of Vamin, alone or in combination with rA1M, did not show any protection of bone marrow cellularity or peripheral reticulocytes. In conclusion, this study suggests that rA1M, administered i.v. for two consecutive days in conjunction with 177Lu-DOTATATE, may reduce hematopoietic and kidney toxicity during PRRT with 177Lu-DOTATATE.

show abstract

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

Cited by 14 publications

References 44 publications

A comparison of simplified protocols of personalized dosimetry in NEN patients treated by radioligand therapy (RLT) with [177Lu]Lu-DOTATATE to favor its use in clinical practice

A comparison of simplified protocols of personalized dosimetry in NEN patients treated by radioligand therapy (RLT) with [177Lu]Lu-DOTATATE to favor its use in clinical practice

Active bone marrow S-values for the low-energy electron emitter terbium-161 compared to S-values for lutetium-177 and yttrium-90

Recombinant α1-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a 177Lu-DOTATATE Mouse Radiation Model

Contact Info

Product

Resources

About