Pelin PELİT ARAYICI, Tayfun ACAR, Mehmet Onur DEMİRKOL, Zeynep MUSTAFAEVA, Burcu UÇAR

[ 68Ga]Ga-AntiCAD1: Radyosentez ve Sıçanlar Üzerinde İlk Görüntüleme Çalışması

Kadherinler, bitişik hücreler arasındaki moleküler bağlantıyı sağlayan, yapışma mekanizmasının başlatılması ve devamı için kritik öneme sahip olan hücre adezyon ve hücre sinyal molekülleridir. N-kadherin ekspresyonu, N-kadherinin artışı ve lezyonların inflamasyonu arasında bir korelasyon sağlar. Bu makalede, adezyonların in vivo PET/CT görüntülenmesi için potansiyel bir aday olarak [68Ga]Ga-AntiCAD1 ajanının radyoişaretlenmesi ve değerlendirmesine odaklanılmıştır. Kimerik antijen reseptörü dizisine dayanan seçici bağlayıcı His-Ala-Val (HAV) motifini içeren (ADH-1)c olarak tasarlanan sentetik N-Ac-CHAVC-NH2 siklik peptid dizisi, N-kadherin antagonisti olarak işlev görür. Yayın aşamasındaki önceki çalışmamızda AntiCAD1 konjugatı ayrıntılı olarak incelenmiştir. Bu çalışmamızda, konjugat, 68Ge/68Ga jeneratöründen (IDB Holland) elde edilen [68Ga]Ga radyonüklidi ile radyoaktif olarak işaretlendi. [68Ga]Ga-AntiCAD1 ajanının radyokimyasal saflığı TLC metodları ile analiz edildi. Ajanın lipofilisitesini belirlemek için P dağılım katsayısı hesaplanarak ‘çalkalama şişesi’ yöntemi uygulandı (logP=- 2.69±0.54). Ajanın biyodağılımı, Wistar Albino sıçanları üzerinde PET/CT kullanılarak araştırıldı. Karaciğer, böbrekler, dalak, tükürük bezi ve hedef bölgede sırasıyla ortalama 1.36, 1.96, 1.38, 1.16 ve 2.14 SUVmax değerleri ile kayda değer oranda tutulum tespit edildi. Hedeflenen bölge ile diğer vücut dokuları arasında olan ilişkini test etmek ve bu ilişkinin derecesini ölçmek için istatistiksel Pearson Faktörü hesaplama yöntemi kullanılmıştır (R=0.73). Sıçan dokularının hedeflenmesinde radyoişaretli ajanın N-kadherin ile spesifik olarak etkileşime girdiği gösterildi.

[ 68Ga]Ga-AntiCAD1: Radiosynthesis and First Imaging Study on Rats

Cadherins are cell adhesion and cell signaling molecules that provide the molecular link between each adjacent cells and have criticalimportance for the initiation and continuation of adhesion mechanism. N-cadherin expression provides a correlation between upregulationof N-cadherin and inflammation of the lesions. In this paper, we concentrated on the radiolabeling and evaluation of [68Ga]Ga-AntiCAD1agent as a potential candidate for in vivo PET/CT imaging of adhesions. The synthetic N-Ac-CHAVC-NH2 cyclic peptide sequence designed as(ADH-1)c containing the selective binding His-Ala-Val (HAV) motif based on the chimeric antigen receptor sequence acts as the N-cadherinantagonist. In our previous study, AntiCAD1 conjugate has been studied in detail which is in the process of publication. In this study, theconjugate was radiolabelled with the [68Ga]Ga radionuclide eluted from the 68Ge/68Ga generator (IDB Holland). Radiochemical purity of[68Ga]Ga-AntiCAD1 agent was analysed with TLC methods. The ‘shake-flask’ method was applied to determine lipophilicity of the agentby calculating the P distribution coefficient (logP=-2.69±0.54). The biodistribution of the agent was investigated using PET/CT on WistarAlbino rats. Significant uptake was found in liver, kidneys, spleen, salivary gland and targeted region with SUVmax-mean of 1.36, 1.96, 1.38, 1.16and 2.14 respectively. The Pearson Factorial method is used to test the relationship between the targeted region and other body tissues, tomeasure the degree of this relationship (R=0.73). Radiolabelled agent was demonstrated to react specifically with N-cadherin in targetingof rat tissues.

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