Inhibition of MDA-MB-231 cell proliferation by pHLIP(Var7)-P1AP and SPECT imaging of MDA-MB-231 breast cancer-bearing nude mice using 125I-pHLIP(Var7)-P1AP

Yue Hua Chen; Ming Ming Yu; Zhen Guang Wang

doi:10.1055/a-1307-1923

Nuklearmedizin - NuclearMedicine, Inhaltsverzeichnis

Nuklearmedizin 2021; 60(03): 240-248
DOI: 10.1055/a-1307-1923

Original Article

Inhibition of MDA-MB-231 cell proliferation by pHLIP(Var7)-P1AP and SPECT imaging of MDA-MB-231 breast cancer-bearing nude mice using ¹²⁵I-pHLIP(Var7)-P1AP

Hemmung der Proliferation von MDA-MB-231-Zellen durch pHLIP (Var7)-P1AP und SPECT-Bildgebung von MDA-MB-231 Mammakarzinom-Nacktmäusen mittels ¹²⁵I-pHLIP (Var7)-P1AP

Yue Hua Chen

¹Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, China

,

Ming Ming Yu

²Nuclear Medicine Department, The Affiliated Hospital of Qingdao University, Qingdao, China

,

Zhen Guang Wang

²Nuclear Medicine Department, The Affiliated Hospital of Qingdao University, Qingdao, China

› Institutsangaben

Abstract

Aim To observe the effect of pHLIP(Var7)-P1AP on the proliferation of MDA-MB-231 triple-negative breast cancer cells and the small-animal single-photon-emission computed tomography (SPECT) imaging of breast cancer–bearing mice carrying MDA-MB-231 cells.

Methods Peptide pHLIP(Var7)-P1AP was synthesized by solid-phase peptide synthesis. The binding of fluorescently labeled pHLIP(Var7)-P1AP to MDA-MB-231 cells under various pH conditions and its effect on MDA-MB-231 cell proliferation were analyzed. pHLIP(Var7)-P1AP was labeled with 125I, and the biological distribution of 125I-pHLIP(Var7)-P1AP in the breast cancer mouse model carrying MDA-MB-231 cells as well as the outcome of small-animal SPECT imaging were evaluated.

Results pHLIP(Var7)-P1AP was successfully synthesized. Under pH 6.0, fluorescently labeled pHLIP(Var7)-P1AP had a higher binding ability to MDA-MB-231 cells and significantly inhibited the proliferation of MDA-MB-231 cells. The labeling efficiency of pHLIP(Var7)-P1AP with 125I was 33.1 ± 2.7 %, and the radiochemical purity was 98.5 ± 1.8 %. 125I-pHLIP(Var7)-P1AP showed a high concentration in tumors. Small-animal SPECT imaging showed clearly visible tumors at 4 h after injection.

Conclusions In the acidic environment, pHLIP(Var7)-P1AP can efficiently target MDA-MB-231 cells and inhibit their growth. Small-animal SPECT of 125I-pHLIP(Var7)-P1AP can clearly image tumors.

Zusammenfassung

Ziel Beobachtung der Wirkung von pHLIP (Var7)-P1AP auf die Proliferation von triple-negativen MDA-MB-231 Mammakarzinomzellen und die Einzelphotonen-Emissions-Computertomografie (SPECT) von MDA-MB-231-Zellen im Mammakarzinom-Mausmodell.

Methoden Das Peptid pHLIP (Var7)-P1AP wurde durch Festphasen-Peptidsynthese synthetisiert. Die Bindung von fluoreszenzmarkiertem pHLIP (Var7)-P1AP an MDA-MB-231-Zellen unter verschiedenen pH-Bedingungen und dessen Wirkung auf die Proliferation von MDA-MB-231-Zellen wurden analysiert. pHLIP (Var7)-P1AP wurde mit ¹²⁵I markiert, und die biologische Verteilung von ¹²⁵I-pHLIP (Var7)-P1AP in dem Mammakarzinom-Mausmodell, das MDA-MB-231-Zellen trägt, sowie das Ergebnis der Kleintier-SPECT-Bildgebung wurden bewertet.

Ergebnisse pHLIP (Var7)-P1AP wurde erfolgreich synthetisiert. Bei einem pH unter 6,0 hatte das fluoreszenzmarkierte pHLIP (Var7)-P1AP eine höhere Bindungsfähigkeit an MDA-MB-231-Zellen und hemmte signifikant die Proliferation von MDA-MB-231-Zellen. Die Markierungseffizienz von pHLIP (Var7)-P1AP mit ¹²⁵I betrug 33,1 ± 2,7 %, und die radiochemische Reinheit betrug 98,5 ± 1,8 %. In Tumoren zeigte ¹²⁵I-pHLIP (Var7)-P1AP eine hohe Konzentration. In der Kleintier-SPECT-Bildgebung zeigten sich 4 h nach Injektion deutlich sichtbare Tumoren.

Schlussfolgerungen Im sauren Milieu kann pHLIP (Var7)-P1AP effizient auf MDA-MB-231-Zellen wirken und deren Wachstum hemmen. Das Kleintier-SPECT mittels ¹²⁵I-pHLIP (Var7)-P1AP kann Tumore klar abbilden.

Key words

pH (low) Insertion Peptides - protease activated receptor 1 - triple negative breast cancer - cell proliferation - small-animal SPECT/CT

Schlüsselwörter

pH (niedrig) Insertionspeptide - Protease-aktivierter Rezeptor 1 - triple-negatives Mammakarzinom - Zellproliferation - Kleintier-SPECT/CT

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Referenzen

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