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@ARTICLE{Tas:289902,
author = {H. Tas$^*$ and G. Bakos$^*$ and U. Bauder-Wüst$^*$ and M.
Schäfer$^*$ and Y. Remde$^*$ and M. Roscher$^*$ and M.
Benesova-Schäfer$^*$},
title = {{H}uman {ABC} and {SLC} {T}ransporters: {T}he {C}ulprit
{R}esponsible for {U}nspecific {PSMA}-617 {U}ptake?},
journal = {Pharmaceuticals},
volume = {17},
number = {4},
issn = {1424-8247},
address = {Basel},
publisher = {MDPI},
reportid = {DKFZ-2024-00894},
pages = {513},
year = {2024},
note = {#EA:E270#LA:E270#},
abstract = {[177Lu]Lu-PSMA-617 has recently been successfully approved
by the FDA, the MHRA, Health Canada and the EMA as
Pluvicto®. However, salivary gland (SG) and kidney
toxicities account for its main dose-limiting side-effects,
while its corresponding uptake and retention mechanisms
still remain elusive. Recently, the presence of different
ATP-binding cassette (ABC) transporters, such as human
breast cancer resistance proteins (BCRP), multidrug
resistance proteins (MDR1), multidrug-resistance-related
proteins (MRP1, MRP4) and solute cassette (SLC)
transporters, such as multidrug and toxin extrusion proteins
(MATE1, MATE2-K), organic anion transporters (OAT1, OAT2v1,
OAT3, OAT4) and peptide transporters (PEPT2), has been
verified at different abundances in human SGs and kidneys.
Therefore, our aim was to assess whether [177Lu]Lu-PSMA-617
and [225Ac]Ac-PSMA-617 are substrates of these ABC and SLC
transporters. For in vitro studies, the novel isotopologue
([α,β-3H]Nal)Lu-PSMA-617 was used in cell lines or
vesicles expressing the aforementioned human ABC and SLC
transporters for inhibition and uptake studies,
respectively. The corresponding probe substrates and
reference inhibitors were used as controls. Our results
indicate that [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 are
neither inhibitors nor substrates of the examined
transporters. Therefore, our results show that human ABC and
SLC transporters play no central role in the uptake and
retention of [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 in
the SGs and kidneys nor in the observed toxicities.},
keywords = {PSMA (Other) / PSMA-617 (Other) / efflux transporters
(Other) / kidney toxicity (Other) / prostate cancer (Other)
/ salivary gland toxicity (Other) / side-effects (Other) /
targeted alpha therapy (Other) / targeted radionuclide
therapy (Other) / uptake transporters (Other)},
cin = {E270 / W630},
ddc = {610},
cid = {I:(DE-He78)E270-20160331 / I:(DE-He78)W630-20160331},
pnm = {315 - Bildgebung und Radioonkologie (POF4-315)},
pid = {G:(DE-HGF)POF4-315},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38675472},
pmc = {pmc:PMC11053447},
doi = {10.3390/ph17040513},
url = {https://inrepo02.dkfz.de/record/289902},
}