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Nanoparticle-Based Radioconjugates for Targeted Imaging and Therapy of Prostate Cancer.

ABSTRACT: Prostate cancer is the second most frequent malignancy in men worldwide and the fifth leading cause of death by cancer. Although most patients initially benefit from therapy, many of them will progress to metastatic castration-resistant prostate cancer, which still remains incurable. The significant mortality and morbidity rate associated with the progression of the disease results mainly from a lack of specific and sensitive prostate cancer screening systems, identification of the disease at mature stages, and failure of anticancer therapy. To overcome the limitations of conventional imaging and therapeutic strategies for prostate cancer, various types of nanoparticles have been designed and synthesized to selectively target prostate cancer cells without causing toxic side effects to healthy organs. The purpose of this review is to briefly discuss the selection criteria of suitable nanoparticles, ligands, radionuclides, and radiolabelling strategies for the development of nanoparticle-based radioconjugates for targeted imaging and therapy of prostate cancer and to evaluate progress in the field, focusing attention on their design, specificity, and potential for detection and/or therapy.

SUBMITTER: Lankoff A

PROVIDER: S-EPMC10223532 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Nanoparticle-Based Radioconjugates for Targeted Imaging and Therapy of Prostate Cancer.

Lankoff Anna A Czerwińska Malwina M Kruszewski Marcin M

Molecules (Basel, Switzerland) 20230516 10

Prostate cancer is the second most frequent malignancy in men worldwide and the fifth leading cause of death by cancer. Although most patients initially benefit from therapy, many of them will progress to metastatic castration-resistant prostate cancer, which still remains incurable. The significant mortality and morbidity rate associated with the progression of the disease results mainly from a lack of specific and sensitive prostate cancer screening systems, identification of the disease at ma ...[more]

PMID: 37241862

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Project description:PurposeThe folate receptor (FR) is frequently overexpressed in a variety of tumor types and, hence, an interesting target for radionuclide therapy. The aim of this study was to evaluate a new class of albumin-binding radioconjugates comprising 5-methyltetrahydrofolate (5-MTHF) as a targeting agent and to compare their properties with those of the previously established folic acid-based [177Lu]Lu-OxFol-1.Methods[177Lu]Lu-6R-RedFol-1 and [177Lu]Lu-6S-RedFol-1 were investigated in vitro using FR-positive KB tumor cells. Biodistribution studies were performed in KB tumor-bearing mice, and the areas under the curve (AUC0 → 120h) were determined for the uptake in tumors and kidneys. [177Lu]Lu-6R-RedFol-1 was compared with [177Lu]Lu-OxFol-1 in a therapy study over 8 weeks using KB tumor-bearing mice.ResultsBoth radioconjugates demonstrated similar in vitro properties as [177Lu]Lu-OxFol-1; however, the tumor uptake of [177Lu]Lu-6R-RedFol-1 and [177Lu]Lu-6S-RedFol-1 was significantly increased in comparison with [177Lu]Lu-OxFol-1. In the case of [177Lu]Lu-6S-RedFol-1, also the kidney uptake was increased; however, renal retention of [177Lu]Lu-6R-RedFol-1 was similar to that of [177Lu]Lu-OxFol-1. This led to an almost 4-fold increased tumor-to-kidney AUC0 → 120h ratio of [177Lu]Lu-6R-RedFol-1 as compared with [177Lu]Lu-6S-RedFol-1 and [177Lu]Lu-OxFol-1. At equal activity, the therapeutic effect of [177Lu]Lu-6R-RedFol-1 was better than that of [177Lu]Lu-OxFol-1, reflected by a slower tumor growth and, consequently, an increased median survival time (49 days vs. 34 days).ConclusionThis study demonstrated the promising potential of 5-MTHF-based radioconjugates for FR-targeting. Application of [177Lu]Lu-6R-RedFol-1 resulted in unprecedentedly high tumor-to-kidney ratios and, as a consequence, a superior therapeutic effect as compared with [177Lu]Lu-OxFol-1. These findings, together with the absence of early side effects, make [177Lu]Lu-6R-RedFol-1 attractive in view of a future clinical translation.

Dataset Information

Nanoparticle-Based Radioconjugates for Targeted Imaging and Therapy of Prostate Cancer.

Publications

Nanoparticle-Based Radioconjugates for Targeted Imaging and Therapy of Prostate Cancer.

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