Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results

Maria Bibika; Panagiotis Kanellopoulos; Maritina Rouchota; George Loudos; Berthold A. Nock; Eric P. Krenning; Theodosia Maina

doi:10.3390/pharmaceutics16091223

Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results

Maria Bibika, Panagiotis Kanellopoulos, Maritina Rouchota, George Loudos, Berthold A. Nock, Eric P. Krenning, Theodosia Maina^*

^*Corresponding author for this work

Radiology & Nuclear Medicine

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background:

The concept of radiotheranostics relies on the overexpression of a biomolecular target on malignant cells to direct diagnostic/therapeutic radionuclide-carriers specifically to cancer lesions. The concomitant expression of more than one target in pathological lesions may be elegantly exploited to improve diagnostic sensitivity and therapeutic efficacy. Toward this goal, we explored a first example of a combined application of [^99mTc]Tc-DT11 (DT11, N₄-Lys(MPBA-PEG4)-Arg-Arg-Pro-Tyr-Ile-Leu-OH; NTS₁R-specific) and [^99mTc]Tc-DB7(DB7, N₄-PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; GRPR-specific) in prostate cancer models.

Methods:

Accordingly, the behavior of [^99mTc]Tc-DT11 was compared with that of the [^99mTc]Tc-DT11+[^99mTc]Tc-DB7 mixture in prostate adenocarcinoma PC-3 cells and xenografts in mice. The impact of stabilizing both radiotracers by Entresto^®, as a source of the potent neprilysin inhibitor sacubitrilat, was also investigated.

Results:

The PC-3 cell binding of the [^99mTc]Tc-DT11+[^99mTc]Tc-DB7 mixture surpassed that of [^99mTc]Tc-DT11. Likewise, the PC-3 tumor uptake of the [^99mTc]Tc-DT11+[^99mTc]Tc-DB7 mixture at 4 h post-injection was superior (7.70 ± 0.89%IA/g) compared with [^99mTc]Tc-DT11 (4.23 ± 0.58%IA/g; p < 0.0001). Treatment with Entresto^® led to further enhancement of the tumor uptake (to 11.57 ± 1.92%IA/g; p < 0.0001).

Conclusions:

In conclusion, this first preclinical study on prostate cancer models revealed clear advantages of dual NTS₁R/GRPR targeting, justifying further assessment of this promising concept in other cancer models.

Original language	English
Article number	1223
Journal	Pharmaceutics
Volume	16
Issue number	9
DOIs	https://doi.org/10.3390/pharmaceutics16091223
Publication status	Published - 19 Sept 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

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Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical ResultsFinal published version, 1.47 MBLicence: CC BY-NC

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@article{916e164247e44b55a443dc8655ae33b6,

title = "Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results",

abstract = "Background: The concept of radiotheranostics relies on the overexpression of a biomolecular target on malignant cells to direct diagnostic/therapeutic radionuclide-carriers specifically to cancer lesions. The concomitant expression of more than one target in pathological lesions may be elegantly exploited to improve diagnostic sensitivity and therapeutic efficacy. Toward this goal, we explored a first example of a combined application of [99mTc]Tc-DT11 (DT11, N4-Lys(MPBA-PEG4)-Arg-Arg-Pro-Tyr-Ile-Leu-OH; NTS1R-specific) and [99mTc]Tc-DB7(DB7, N4-PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; GRPR-specific) in prostate cancer models. Methods: Accordingly, the behavior of [99mTc]Tc-DT11 was compared with that of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture in prostate adenocarcinoma PC-3 cells and xenografts in mice. The impact of stabilizing both radiotracers by Entresto{\textregistered}, as a source of the potent neprilysin inhibitor sacubitrilat, was also investigated. Results: The PC-3 cell binding of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture surpassed that of [99mTc]Tc-DT11. Likewise, the PC-3 tumor uptake of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture at 4 h post-injection was superior (7.70 ± 0.89%IA/g) compared with [99mTc]Tc-DT11 (4.23 ± 0.58%IA/g; p < 0.0001). Treatment with Entresto{\textregistered} led to further enhancement of the tumor uptake (to 11.57 ± 1.92%IA/g; p < 0.0001).Conclusions:In conclusion, this first preclinical study on prostate cancer models revealed clear advantages of dual NTS1R/GRPR targeting, justifying further assessment of this promising concept in other cancer models.",

author = "Maria Bibika and Panagiotis Kanellopoulos and Maritina Rouchota and George Loudos and Nock, {Berthold A.} and Krenning, {Eric P.} and Theodosia Maina",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

year = "2024",

month = sep,

day = "19",

doi = "10.3390/pharmaceutics16091223",

language = "English",

volume = "16",

journal = "Pharmaceutics",

issn = "1999-4923",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

TY - JOUR

T1 - Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results

AU - Bibika, Maria

AU - Kanellopoulos, Panagiotis

AU - Rouchota, Maritina

AU - Loudos, George

AU - Nock, Berthold A.

AU - Krenning, Eric P.

AU - Maina, Theodosia

PY - 2024/9/19

Y1 - 2024/9/19

N2 - Background: The concept of radiotheranostics relies on the overexpression of a biomolecular target on malignant cells to direct diagnostic/therapeutic radionuclide-carriers specifically to cancer lesions. The concomitant expression of more than one target in pathological lesions may be elegantly exploited to improve diagnostic sensitivity and therapeutic efficacy. Toward this goal, we explored a first example of a combined application of [99mTc]Tc-DT11 (DT11, N4-Lys(MPBA-PEG4)-Arg-Arg-Pro-Tyr-Ile-Leu-OH; NTS1R-specific) and [99mTc]Tc-DB7(DB7, N4-PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; GRPR-specific) in prostate cancer models. Methods: Accordingly, the behavior of [99mTc]Tc-DT11 was compared with that of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture in prostate adenocarcinoma PC-3 cells and xenografts in mice. The impact of stabilizing both radiotracers by Entresto®, as a source of the potent neprilysin inhibitor sacubitrilat, was also investigated. Results: The PC-3 cell binding of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture surpassed that of [99mTc]Tc-DT11. Likewise, the PC-3 tumor uptake of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture at 4 h post-injection was superior (7.70 ± 0.89%IA/g) compared with [99mTc]Tc-DT11 (4.23 ± 0.58%IA/g; p < 0.0001). Treatment with Entresto® led to further enhancement of the tumor uptake (to 11.57 ± 1.92%IA/g; p < 0.0001).Conclusions:In conclusion, this first preclinical study on prostate cancer models revealed clear advantages of dual NTS1R/GRPR targeting, justifying further assessment of this promising concept in other cancer models.

AB - Background: The concept of radiotheranostics relies on the overexpression of a biomolecular target on malignant cells to direct diagnostic/therapeutic radionuclide-carriers specifically to cancer lesions. The concomitant expression of more than one target in pathological lesions may be elegantly exploited to improve diagnostic sensitivity and therapeutic efficacy. Toward this goal, we explored a first example of a combined application of [99mTc]Tc-DT11 (DT11, N4-Lys(MPBA-PEG4)-Arg-Arg-Pro-Tyr-Ile-Leu-OH; NTS1R-specific) and [99mTc]Tc-DB7(DB7, N4-PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; GRPR-specific) in prostate cancer models. Methods: Accordingly, the behavior of [99mTc]Tc-DT11 was compared with that of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture in prostate adenocarcinoma PC-3 cells and xenografts in mice. The impact of stabilizing both radiotracers by Entresto®, as a source of the potent neprilysin inhibitor sacubitrilat, was also investigated. Results: The PC-3 cell binding of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture surpassed that of [99mTc]Tc-DT11. Likewise, the PC-3 tumor uptake of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture at 4 h post-injection was superior (7.70 ± 0.89%IA/g) compared with [99mTc]Tc-DT11 (4.23 ± 0.58%IA/g; p < 0.0001). Treatment with Entresto® led to further enhancement of the tumor uptake (to 11.57 ± 1.92%IA/g; p < 0.0001).Conclusions:In conclusion, this first preclinical study on prostate cancer models revealed clear advantages of dual NTS1R/GRPR targeting, justifying further assessment of this promising concept in other cancer models.

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DO - 10.3390/pharmaceutics16091223

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AN - SCOPUS:85205108763

SN - 1999-4923

VL - 16

JO - Pharmaceutics

JF - Pharmaceutics

IS - 9

M1 - 1223

ER -

Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results

Abstract

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