Development of PSMA-targeted vectors containing an albumin binder and a cleavable linker

Erika Murce; Stephen Ahenkorah; Erik de Blois; Frederik Cleeren; Marion de Jong; Yann Seimbille

doi:10.1016/S0969-8051(22)00133-0

Development of PSMA-targeted vectors containing an albumin binder and a cleavable linker

Erika Murce, Stephen Ahenkorah, Erik de Blois, Frederik Cleeren, Marion de Jong, Yann Seimbille

Research output › peer-review

Abstract

Peptide receptor radionuclide therapy (PRRT) is a promising strategy to treat several types of cancer. Particular attention was devoted to the development of vectors for the treatment of prostate cancer over the last two decades. The most successful candidates are currently being tested in clinical trials. Addition of an albuminbinder to the targeting vector can enhance the dose delivered to
tumors, and substantially to some healthy organs. A common drawback
of this therapy is off-target side-effects. Elevated renal uptake is
commonly observed with compounds targeting the prostate specific
membrane antigen (PSMA), limiting the dose of radiopharmaceutical
administered. Hereby, we aimed to apply a cleavable linker strategy, where amino-acid sequences are specifically cleaved by renal brush border membrane (RBBM) enzymes to decrease the absorbed dose delivered to the kidneys. By employing both the albumin-binder and cleavable linker strategies, we advanced the development of optimized constructs with increased therapeutic efficacy and safety profile.

Original language	English
Title of host publication	Nuclear Medicine and Biology
Subtitle of host publication	Abstract of the international symposium on radiopharmaceutical science iSRS 2022
Publisher	Elsevier
Pages	S48-S49
Number of pages	2
Volume	108-109
Edition	May-June
DOIs	https://doi.org/10.1016/S0969-8051(22)00133-0
State	Published - May 2022

Publication series

Name	Nuclear Medicine and Biology
Publisher	Elsevier
Number	3MT-7
Volume	108-109
ISSN (Print)	0969-8051
ISSN (Electronic)	1872-9614

Access to Document

10.1016/S0969-8051(22)00133-0License: Unspecified

Cite this

Murce, E., Ahenkorah, S., de Blois, E., Cleeren, F., de Jong, M., & Seimbille, Y. (2022). Development of PSMA-targeted vectors containing an albumin binder and a cleavable linker. In Nuclear Medicine and Biology: Abstract of the international symposium on radiopharmaceutical science iSRS 2022 (May-June ed., Vol. 108-109, pp. S48-S49). [3MT-7] (Nuclear Medicine and Biology; Vol. 108-109, No. 3MT-7). Elsevier. https://doi.org/10.1016/S0969-8051(22)00133-0

Murce, Erika ; Ahenkorah, Stephen ; de Blois, Erik ; Cleeren, Frederik ; de Jong, Marion ; Seimbille, Yann. / Development of PSMA-targeted vectors containing an albumin binder and a cleavable linker. Nuclear Medicine and Biology: Abstract of the international symposium on radiopharmaceutical science iSRS 2022. Vol. 108-109 May-June. ed. Elsevier, 2022. pp. S48-S49 (Nuclear Medicine and Biology; 3MT-7).

@inproceedings{9d45e16fdbbc4896b7056be24c98c178,

title = "Development of PSMA-targeted vectors containing an albumin binder and a cleavable linker",

abstract = "Peptide receptor radionuclide therapy (PRRT) is a promising strategy to treat several types of cancer. Particular attention was devoted to the development of vectors for the treatment of prostate cancer over the last two decades. The most successful candidates are currently being tested in clinical trials. Addition of an albuminbinder to the targeting vector can enhance the dose delivered totumors, and substantially to some healthy organs. A common drawbackof this therapy is off-target side-effects. Elevated renal uptake iscommonly observed with compounds targeting the prostate specificmembrane antigen (PSMA), limiting the dose of radiopharmaceuticaladministered. Hereby, we aimed to apply a cleavable linker strategy, where amino-acid sequences are specifically cleaved by renal brush border membrane (RBBM) enzymes to decrease the absorbed dose delivered to the kidneys. By employing both the albumin-binder and cleavable linker strategies, we advanced the development of optimized constructs with increased therapeutic efficacy and safety profile.",

keywords = "PSMA-targeted radionuclide therapy, PRRT, Cancer treatment",

author = "Erika Murce and Stephen Ahenkorah and {de Blois}, Erik and Frederik Cleeren and {de Jong}, Marion and Yann Seimbille",

note = "Score=3",

year = "2022",

month = may,

doi = "10.1016/S0969-8051(22)00133-0",

language = "English",

volume = "108-109",

series = "Nuclear Medicine and Biology",

publisher = "Elsevier",

number = "3MT-7",

pages = "S48--S49",

booktitle = "Nuclear Medicine and Biology",

address = "Netherlands",

edition = "May-June",

}

Murce, E, Ahenkorah, S, de Blois, E, Cleeren, F, de Jong, M & Seimbille, Y 2022, Development of PSMA-targeted vectors containing an albumin binder and a cleavable linker. in Nuclear Medicine and Biology: Abstract of the international symposium on radiopharmaceutical science iSRS 2022. May-June edn, vol. 108-109, 3MT-7, Nuclear Medicine and Biology, no. 3MT-7, vol. 108-109, Elsevier, pp. S48-S49. https://doi.org/10.1016/S0969-8051(22)00133-0

Development of PSMA-targeted vectors containing an albumin binder and a cleavable linker. / Murce, Erika; Ahenkorah, Stephen; de Blois, Erik; Cleeren, Frederik; de Jong, Marion; Seimbille, Yann.

Nuclear Medicine and Biology: Abstract of the international symposium on radiopharmaceutical science iSRS 2022. Vol. 108-109 May-June. ed. Elsevier, 2022. p. S48-S49 3MT-7 (Nuclear Medicine and Biology; Vol. 108-109, No. 3MT-7).

Research output › peer-review

TY - GEN

T1 - Development of PSMA-targeted vectors containing an albumin binder and a cleavable linker

AU - Murce, Erika

AU - Ahenkorah, Stephen

AU - de Blois, Erik

AU - Cleeren, Frederik

AU - de Jong, Marion

AU - Seimbille, Yann

N1 - Score=3

PY - 2022/5

Y1 - 2022/5

N2 - Peptide receptor radionuclide therapy (PRRT) is a promising strategy to treat several types of cancer. Particular attention was devoted to the development of vectors for the treatment of prostate cancer over the last two decades. The most successful candidates are currently being tested in clinical trials. Addition of an albuminbinder to the targeting vector can enhance the dose delivered totumors, and substantially to some healthy organs. A common drawbackof this therapy is off-target side-effects. Elevated renal uptake iscommonly observed with compounds targeting the prostate specificmembrane antigen (PSMA), limiting the dose of radiopharmaceuticaladministered. Hereby, we aimed to apply a cleavable linker strategy, where amino-acid sequences are specifically cleaved by renal brush border membrane (RBBM) enzymes to decrease the absorbed dose delivered to the kidneys. By employing both the albumin-binder and cleavable linker strategies, we advanced the development of optimized constructs with increased therapeutic efficacy and safety profile.

AB - Peptide receptor radionuclide therapy (PRRT) is a promising strategy to treat several types of cancer. Particular attention was devoted to the development of vectors for the treatment of prostate cancer over the last two decades. The most successful candidates are currently being tested in clinical trials. Addition of an albuminbinder to the targeting vector can enhance the dose delivered totumors, and substantially to some healthy organs. A common drawbackof this therapy is off-target side-effects. Elevated renal uptake iscommonly observed with compounds targeting the prostate specificmembrane antigen (PSMA), limiting the dose of radiopharmaceuticaladministered. Hereby, we aimed to apply a cleavable linker strategy, where amino-acid sequences are specifically cleaved by renal brush border membrane (RBBM) enzymes to decrease the absorbed dose delivered to the kidneys. By employing both the albumin-binder and cleavable linker strategies, we advanced the development of optimized constructs with increased therapeutic efficacy and safety profile.

KW - PSMA-targeted radionuclide therapy

KW - PRRT

KW - Cancer treatment

UR - https://doi.org/10.1016/S0969-8051(22)00133-0

U2 - 10.1016/S0969-8051(22)00133-0

DO - 10.1016/S0969-8051(22)00133-0

M3 - In-proceedings paper

VL - 108-109

T3 - Nuclear Medicine and Biology

SP - S48-S49

BT - Nuclear Medicine and Biology

PB - Elsevier

ER -

Murce E, Ahenkorah S, de Blois E, Cleeren F, de Jong M, Seimbille Y. Development of PSMA-targeted vectors containing an albumin binder and a cleavable linker. In Nuclear Medicine and Biology: Abstract of the international symposium on radiopharmaceutical science iSRS 2022. May-June ed. Vol. 108-109. Elsevier. 2022. p. S48-S49. 3MT-7. (Nuclear Medicine and Biology; 3MT-7). https://doi.org/10.1016/S0969-8051(22)00133-0