Hematological and renal toxicity in mice after three cycles of high activity [177Lu]Lu-PSMA-617 with or without human α1-microglobulin
Kristiansson, Amanda LU ; Vilhelmsson Timmermand, Oskar LU ; Altai, Mohamed LU ; Strand, Sven-Erik LU ; Åkerström, Bo LU and Örbom, Anders LU
(2024)
In Scientific Reports
14(1).
- Abstract
- Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a... (More)
- Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a human antioxidant previously shown to have radioprotective effects. In both groups, three cycles resulted in increased albuminuria for each cycle, with large individual variation. Another marker of kidney injury, serum blood urea nitrogen (BUN), was only significantly increased compared to control animals after the third cycle. The number of white and red blood cells decreased significantly and did not reach the levels of control animals during the experiment. rA1M did reduce absorbed dose to kidney but did not show significant protection here, but future studies are warranted due to the recent clinical studies showing a significant renoprotective effect in patients. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/b941cde1-ba97-4cf0-b0d2-39577ab6d17c
- author
- Kristiansson, Amanda
LU
; Vilhelmsson Timmermand, Oskar
LU
; Altai, Mohamed
LU
; Strand, Sven-Erik
LU
; Åkerström, Bo
LU
and Örbom, Anders
LU
- organization
- publishing date
- 2024-05-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 14
- issue
- 1
- article number
- 10787
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85192900746
- pmid:38734765
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-024-61370-2
- language
- English
- LU publication?
- yes
- id
- b941cde1-ba97-4cf0-b0d2-39577ab6d17c
- date added to LUP
- 2024-05-11 13:30:03
- date last changed
- 2024-11-20 21:00:56
@article{b941cde1-ba97-4cf0-b0d2-39577ab6d17c,
abstract = {{Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a human antioxidant previously shown to have radioprotective effects. In both groups, three cycles resulted in increased albuminuria for each cycle, with large individual variation. Another marker of kidney injury, serum blood urea nitrogen (BUN), was only significantly increased compared to control animals after the third cycle. The number of white and red blood cells decreased significantly and did not reach the levels of control animals during the experiment. rA1M did reduce absorbed dose to kidney but did not show significant protection here, but future studies are warranted due to the recent clinical studies showing a significant renoprotective effect in patients.}},
author = {{Kristiansson, Amanda and Vilhelmsson Timmermand, Oskar and Altai, Mohamed and Strand, Sven-Erik and Åkerström, Bo and Örbom, Anders}},
issn = {{2045-2322}},
language = {{eng}},
month = {{05}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Hematological and renal toxicity in mice after three cycles of high activity [177Lu]Lu-PSMA-617 with or without human α1-microglobulin}},
url = {{http://dx.doi.org/10.1038/s41598-024-61370-2}},
doi = {{10.1038/s41598-024-61370-2}},
volume = {{14}},
year = {{2024}},
}