Covalent core-radiolabeling of polymeric micelles with125I/211At for theranostic radiotherapy
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Covalent core-radiolabeling of polymeric micelles with125I/211At for theranostic radiotherapy. / Sporer, Emanuel; Poulie, Christian B.M.; Bäck, Tom; Lindegren, Sture; Jensen, Holger; Kempen, Paul J.; Kjaer, Andreas; Herth, Matthias M.; Jensen, Andreas I.
I: Nanotheranostics, Bind 6, Nr. 4, 2022, s. 388-399.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Covalent core-radiolabeling of polymeric micelles with125I/211At for theranostic radiotherapy
AU - Sporer, Emanuel
AU - Poulie, Christian B.M.
AU - Bäck, Tom
AU - Lindegren, Sture
AU - Jensen, Holger
AU - Kempen, Paul J.
AU - Kjaer, Andreas
AU - Herth, Matthias M.
AU - Jensen, Andreas I.
N1 - Publisher Copyright: © The author(s).
PY - 2022
Y1 - 2022
N2 - Astatine-211 (211At) is one of the most promising α-emitters for targeted alpha therapy, especially of cancer metastases. However, the lack of a stable isotope, frequent in vivo deastatination, and limited radiochemical knowledge makes it challenging to apply. Here, we report a new strategy for radiolabeling the lipophilic core of polymeric micelles (PMs) with covalently bound211At. The PMs were radiolabeled via either an indirect synthon-based method or directly on the amphipathic block copolymer. The radiochemistry was optimized with iodine-125 (125I) and then adapted for211At, enabling the use of both elements as a potential theranostic pair. PMs that were core-radiolabeled with both125I or211At were prepared and characterized, based on a PEG(5k)-PLGA(10k) co-polymer. The stability of the radiolabeled PMs was evaluated in mouse serum for 21 h, showing radiochemical stability above 85%. After in vivo evaluation of the211At-labeled PMs, 4-5 % ID/g of the211At could still be detected in the blood, showing a promising in vivo stability of the PMs. Further,211At-labeled PMs accumulated in the spleen (20-30 %ID/g) and the liver (2.5-5.5 %ID/g), along with some detection of211At in the thyroid (3.5-9 %ID/g). This led to the hypothesis that deastatination takes place in the liver, whereas good stability of the211At core-radiolabel was observed in the blood.
AB - Astatine-211 (211At) is one of the most promising α-emitters for targeted alpha therapy, especially of cancer metastases. However, the lack of a stable isotope, frequent in vivo deastatination, and limited radiochemical knowledge makes it challenging to apply. Here, we report a new strategy for radiolabeling the lipophilic core of polymeric micelles (PMs) with covalently bound211At. The PMs were radiolabeled via either an indirect synthon-based method or directly on the amphipathic block copolymer. The radiochemistry was optimized with iodine-125 (125I) and then adapted for211At, enabling the use of both elements as a potential theranostic pair. PMs that were core-radiolabeled with both125I or211At were prepared and characterized, based on a PEG(5k)-PLGA(10k) co-polymer. The stability of the radiolabeled PMs was evaluated in mouse serum for 21 h, showing radiochemical stability above 85%. After in vivo evaluation of the211At-labeled PMs, 4-5 % ID/g of the211At could still be detected in the blood, showing a promising in vivo stability of the PMs. Further,211At-labeled PMs accumulated in the spleen (20-30 %ID/g) and the liver (2.5-5.5 %ID/g), along with some detection of211At in the thyroid (3.5-9 %ID/g). This led to the hypothesis that deastatination takes place in the liver, whereas good stability of the211At core-radiolabel was observed in the blood.
KW - alpha-therapy
KW - Astatine-211
KW - iodine-125
KW - PEG-PLGA
KW - polymeric micelles
UR - http://www.scopus.com/inward/record.url?scp=85134598082&partnerID=8YFLogxK
U2 - 10.7150/ntno.71906
DO - 10.7150/ntno.71906
M3 - Journal article
C2 - 35912139
AN - SCOPUS:85134598082
VL - 6
SP - 388
EP - 399
JO - Nanotheranostics
JF - Nanotheranostics
SN - 2206-7418
IS - 4
ER -
ID: 317513769