Dataset Information

Preclinical evaluation of 5-methyltetrahydrofolate-based radioconjugates-new perspectives for folate receptor-targeted radionuclide therapy.

ABSTRACT:

Purpose

The 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 (AUC_{0 → 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.

Results

Both 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 AUC_{0 → 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).

Conclusion

This 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.

SUBMITTER: Guzik P

PROVIDER: S-EPMC8041685 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Preclinical evaluation of 5-methyltetrahydrofolate-based radioconjugates-new perspectives for folate receptor-targeted radionuclide therapy.

Guzik Patrycja P Benešová Martina M Ratz Magdalena M Monné Rodríguez Josep M JM Deberle Luisa M LM Schibli Roger R Müller Cristina C

European journal of nuclear medicine and molecular imaging 20201015 4

<h4>Purpose</h4>The 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 [<sup>177</sup>Lu]Lu-OxFol-1.<h4>Methods</h4>[<sup>177</sup>Lu]Lu-6R-RedFol-1 and [<sup>177</sup>Lu]Lu ...[more]

PMID: 33063250

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Dataset Information

Preclinical evaluation of 5-methyltetrahydrofolate-based radioconjugates-new perspectives for folate receptor-targeted radionuclide therapy.

Purpose

Methods

Results

Conclusion

Publications

Preclinical evaluation of 5-methyltetrahydrofolate-based radioconjugates-new perspectives for folate receptor-targeted radionuclide therapy.

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