fa 1-(3-نیتروپریدین-2-ایل) پیپرازین نشاندارشده با تکنسیوم تری کربونیل به عنوان رادیولیگاند بالقوه برای گیرنده‌های 5-HT7 داروسازی هسته ای Nuclear pharmacy پژوهشي-کامل Research(Original) <span style="line-height:2;"><span style="font-size:12pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><span b="" koodak="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt">سابقه</span></span></span><span b="" koodak="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt"> و </span></span></span><span b="" koodak="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt">هدف:</span></span></span> <span b="" style="font-family:" zar=""><span style="color:black">خانواده گیرنده سروتونین </span></span><span dir="LTR" style="font-size:10.0pt">(5-HTR)</span><span b="" style="font-family:" zar=""><span style="color:black"> شامل 7 عضو مختلف است. گیرنده سروتونین 7 (</span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">5-HT₇R</span></span><span b="" style="font-family:" zar=""><span style="color:black">) <span style="letter-spacing:-.2pt">جدیدترین عضو این خانواده است. </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt">5-HT₇R</span></span><span b="" style="font-family:" zar=""><span style="color:black"><span style="letter-spacing:-.2pt"> در فرآیندهای فیزیولوژیکی و پاتولوژیک مختلف از جمله گلیوبلاستوما مولتی‌فرم</span></span></span><span b="" style="font-family:" zar=""><span style="color:black"> (</span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">GBM</span></span><span b="" style="font-family:" zar=""><span style="color:black">) دخالت دارد. درمان استاندارد </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">GBM</span></span><span b="" style="font-family:" zar=""><span style="color:black"> ترکیبی از جراحی، رادیوتراپی و شیمی درمانی است. با این حال، تومورهای </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">GBM</span></span><span b="" style="font-family:" zar=""><span style="color:black"> بسیار پراکنده هستند و احتمال عود بالایی دارند، بنابراین استفاده از تکنیک‌های نظارتی مختلف مانند تصویربرداری <span style="letter-spacing:-.1pt">پزشکی هسته‌ای ضروری است. هدف از این مطالعه ارائه یک رادیوتریسر (</span></span></span><em><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span style="color:black"><span style="letter-spacing:-.1pt"><span style="font-style:normal">Radiotracer</span></span></span></span></span></em><span b="" style="font-family:" zar=""><span style="color:black"><span style="letter-spacing:-.1pt">) مناسب برای تصویربرداری از بیان بیش از حد </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black"><span style="letter-spacing:-.1pt">5-HT₇R</span></span></span><span b="" style="font-family:" zar=""><span style="color:black"><span style="letter-spacing:-.1pt"> در گلیوبلاستوما مولتی فرم با استفاده از مشتق آریل پیپرازین نشاندار شده </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.1pt">(</span></span>^{<span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.1pt">99m</span></span>}<span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.1pt">Tc(CO)₃-[<b>5</b>]</span></span><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.1pt">)</span></span><span b="" style="font-family:" zar=""><span style="letter-spacing:-.1pt"> <span lang="FA" style="color:black">است.</span></span></span><span b="" style="font-family:" zar=""><span style="color:#0e101a"></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><span b="" koodak="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt">مواد و روش</span></span></span><span b="" style="font-family:" zar=""><span style="color:black"><span style="letter-spacing:-.1pt">‌</span></span></span><span b="" koodak="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt">ها:</span></span></span> <span b="" style="font-family:" zar="">در مطالعه تجربی حاضر، </span><span b="" style="font-family:" zar="">1</span><span b="" style="font-family:" zar=""><span style="color:black"><span style="letter-spacing:-.1pt">-(3-نیتروپریدین-2-ایل)پیپرازین</span></span></span><span b="" style="font-family:" zar=""><span style="color:black"> (ترکیب </span></span><b><span b="" nazanin="" style="font-family:"><span style="color:black">5</span></span></b><span b="" style="font-family:" zar=""><span style="color:black">) <span style="letter-spacing:-.1pt">طراحی، سنتز، شناسایی </span>و با </span></span><i><span dir="LTR" style="font-size:10.0pt">fac</span></i><span dir="LTR" style="font-size:10.0pt">-[^99mTc(CO)₃(H₂O)₃]⁺</span><span b="" style="font-family:" zar=""> نشاندار شد</span><span b="" style="font-family:" zar=""><span style="color:black"> و </span></span>^{<span dir="LTR" style="font-size:10.0pt">99m</span>}<span dir="LTR" style="font-size:10.0pt">Tc(CO)₃-[<b>5</b>]</span><span b="" style="font-family:" zar=""><span style="color:black"> با خلوص رادیوشیمیایی کمی به‌حدست آمد. آزمایش‌های <span style="letter-spacing:-.2pt">کنترل کیفیت شامل </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black"><span style="letter-spacing:-.2pt">HPLC</span></span></span><span b="" style="font-family:" zar=""><span style="color:black"><span style="letter-spacing:-.2pt"> و </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black"><span style="letter-spacing:-.2pt">TLC</span></span></span><span b="" style="font-family:" zar=""><span style="color:black"><span style="letter-spacing:-.2pt"> برای تعیین خلوص رادیوشیمیایی انجام شد. مطالعه اتصال اختصاصی با استفاده از رده‌های</span></span></span><span b="" style="font-family:" zar=""><span style="color:black"> سلولی مختلف (</span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">U-87 MG</span></span><span b="" style="font-family:" zar=""><span style="color:black">، </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">MCF-7</span></span><span b="" style="font-family:" zar=""><span style="color:black">، </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">SKBR3</span></span><span b="" style="font-family:" zar=""><span style="color:black">، </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">HT-29</span></span><span b="" style="font-family:" zar=""><span style="color:black"> و </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">A549</span></span><span b="" style="font-family:" zar=""><span style="color:black">) انجام شد. میل ترکیبی </span></span>^{<span dir="LTR" style="font-size:10.0pt">99m</span>}<span dir="LTR" style="font-size:10.0pt">Tc(CO)₃-[<b>5</b>]</span><span b="" style="font-family:" zar=""><span style="color:black"> به </span></span><span dir="LTR" style="font-size:10.0pt">5-HT₇R</span><span b="" style="font-family:" zar=""><span style="color:black"> بیان شده در سطح رده سلولی </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">U87-MG</span></span><span b="" style="font-family:" zar=""><span style="color:black"> با استفاده از ثابت تفکیک (</span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">Kd</span></span><span b="" style="font-family:" zar=""><span style="color:black">) و </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">Bmax</span></span><span b="" style="font-family:" zar=""><span style="color:black"> ارزیابی شد.<span style="letter-spacing:-.2pt"></span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><span b="" koodak="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.2pt">یافته</span></span></span><span b="" style="font-family:" zar=""><span style="color:black"><span style="letter-spacing:-.2pt">‌</span></span></span><span b="" koodak="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.2pt">ها:</span></span></span> <span b="" style="font-family:" zar=""><span style="color:black">خلوص رادیوشیمیایی اولیه</span></span> ^{<span dir="LTR" style="font-size:10.0pt">99m</span>}<span dir="LTR" style="font-size:10.0pt">Tc(CO)₃-[<b>5</b>]</span> <span b="" style="font-family:" zar=""><span style="color:black">بیش از 95 درصد بود. این رادیوتریسر </span></span><span b="" style="font-family:" zar=""><span style="color:black">تمایل متوسطی را به گیرنده‌های </span></span><span dir="LTR" style="font-size:10.0pt">5-HT₇R</span><span b="" style="font-family:" zar=""> در</span><span b="" style="font-family:" zar=""><span style="color:black"> رده سلولی </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">U87-MG</span></span><span b="" style="font-family:" zar=""><span style="color:black"> نشان داد، در حالی که تمایل کمی برای اتصال به </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">MCF-7</span></span><span b="" style="font-family:" zar=""><span style="color:black">، </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">SKBR3</span></span><span b="" style="font-family:" zar=""><span style="color:black">، </span></span><br> <span dir="LTR" style="font-size:10.0pt"><span style="color:black">HT-29</span></span><span b="" style="font-family:" zar=""><span style="color:black"> و </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">A549</span></span><span b="" style="font-family:" zar=""><span style="color:black"> دارد. </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">B_max</span></span><span b="" style="font-family:" zar=""><span style="color:black"> و ثابت تفکیک (</span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">Kd</span></span><span b="" style="font-family:" zar=""><span style="color:black">) به ترتیب9/23</span></span><span lang="FA" style="font-size:10.0pt"><span style="color:black">&plusmn;</span></span><span b="" style="font-family:" zar=""><span style="color:black">48 نانو مولار و </span></span><span b="" style="font-family:" zar="">10⁵</span><span b="" style="font-family:" zar="">&times;0/09</span><span lang="AR-SA" style="font-size:10.0pt">&plusmn;</span><span b="" style="font-family:" zar="">2/94</span> <span b="" style="font-family:" zar=""><span style="color:black">محاسبه ‌شدند.</span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><span lang="AR-SA" style="font-size:11.5pt"><span b="" koodak="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.2pt">استنتاج:</span></span></span></span> <span b="" style="font-family:" zar="">براساس یافته</span><span b="" style="font-family:" zar=""><span style="color:black">‌</span></span><span b="" style="font-family:" zar="">های این مطالعه، ترکیب </span><b><span b="" nazanin="" style="font-family:">5</span></b><span b="" style="font-family:" zar=""><span style="color:black"> را می‌توان به صورت کمی با </span></span><i><span dir="LTR" style="font-size:10.0pt">fac</span></i><span dir="LTR" style="font-size:10.0pt">-[^99mTc(CO)₃(H₂O)₃]⁺</span><span b="" style="font-family:" zar=""><span style="color:black">نشاندار کرد. رادیوتریسر تهیه شده </span></span>^{<span dir="LTR" style="font-size:10.0pt">99m</span>}<span dir="LTR" style="font-size:10.0pt">Tc(CO)₃-[<b>5</b>]</span><span b="" style="font-family:" zar=""><span style="color:black"> به گیرنده‌های </span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">5-HT₇R</span></span><span b="" style="font-family:" zar=""><span style="color:black"> رده سلولی</span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black">U87-MG</span></span><span b="" style="font-family:" zar=""><span style="color:black"> با میل ترکیبی متوسط متصل می‌شد.</span></span><span b="" style="font-family:" zar=""><span style="color:black"><span style="letter-spacing:-.2pt"></span></span></span></span></span></span></span></span><br> &nbsp; <span style="line-height:2;"><span style="font-size:12pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:10.0pt"><span arial="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt">Background and purpose:</span></span></span></span></b> <span style="font-size:10.0pt"><span style="color:black">The serotonin receptor (5-HTR) family includes seven distinct members, with the serotonin seven receptor (5-HT7R) being the newest addition to this family. The </span></span><br> <span style="font-size:10.0pt"><span style="color:black">5-HT₇R contributes to different</span></span> <span style="font-size:10.0pt"><span style="color:black">physiological and pathological processes including glioblastoma</span></span> <span style="font-size:10.0pt"><span style="color:black">multiforme (GBM).</span></span> <span style="font-size:10.0pt"><span style="color:black">The standard treatment for GBM involves a combination of surgery, radiotherapy and chemotherapy. However, GBM tumors are highly diffuse and exhibit a significant risk of recurrence. As a result, the use of advanced monitoring techniques, such as nuclear medicine imaging, is essential. This study aims to develop an effective radiotracer for imaging 5-HT7R overexpression in GBM by utilizing a radiolabeled aryl piperazine derivative (</span></span>^{<span style="font-size:10.0pt"><span style="color:black">99m</span></span>}<span style="font-size:10.0pt"><span style="color:black">Tc(CO)₃-[<b>5</b>]</span></span><span style="font-size:10.0pt"><span style="color:black">).</span></span></span></span><br> <span style="font-size:12pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:10.0pt"><span arial="" style="font-family:"><span style="color:black">Materials and methods</span></span></span></b><b><span style="font-size:10.0pt"><span arial="" style="font-family:">:</span></span></b><b> </b><span lang="EN" style="font-size:10.0pt">In this experimental study<span style="color:black">,</span></span> <span style="font-size:10.0pt"><span style="color:black">compound <b>5</b> </span></span><span style="font-size:10.0pt"><span style="color:black">1-(3-nitropyridin-2-yl) piperazine </span></span><span style="font-size:10.0pt"><span style="color:black">was designed, synthesized, and characterized, then radiolabeled with </span></span><i><span style="font-size:10.0pt"><span style="color:black">fac</span></span></i><span style="font-size:10.0pt"><span style="color:black">-[^99mTc(CO)₃(H₂O)₃]⁺to produce </span></span>^{<span style="font-size:10.0pt"><span style="color:black">99m</span></span>}<span style="font-size:10.0pt"><span style="color:black">Tc(CO)₃-[<b>5</b>]. Quality control tests, including high-حperformance liquid chromatography (HPLC) and thin-layer chromatography (TLC) were performed to determine the radiochemical purity. The specific binding study was performed using various cell lines, including U-87 MG, MCF-7, SKBR3, HT-29, and A549. The affinity of </span></span>^{<span style="font-size:10.0pt"><span style="color:black">99m</span></span>}<span style="font-size:10.0pt"><span style="color:black">Tc(CO)₃-[<b>5</b>] for 5-HT₇R was evaluated using the U87-MG cell line</span></span><span style="font-size:10.0pt"><span style="color:black"> and the maximum binding capacity (B_max,) and </span></span><span style="font-size:10.0pt"><span style="color:black">dissociation constant (K_d) were calculated.</span></span></span></span><br> <span style="font-size:12pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:10.0pt"><span arial="" style="font-family:"><span style="color:black">Results: </span></span></span></b><span style="font-size:10.0pt"><span style="color:black">The initial radiochemical purity of ^99mTc(CO)₃-[<b>5</b>] was greater </span></span><span style="font-size:10.0pt"><span style="color:black">than 95% (RCP>95%). This radiotracer</span></span><span style="font-size:10.0pt"><span style="color:black"> displayed moderate affinity for the U87-MG cell line&rsquo;s 5-HT₇R and lower affinity for </span></span><span style="font-size:10.0pt"><span style="color:black">MCF-7, SKBR3, HT-29, and A549 cell lines. The calculated B_max, and </span></span><span style="font-size:10.0pt"><span style="color:black">K_d of the radioligands were 48&plusmn;9.23nM and 2.94&plusmn;0.09&times;10⁵.</span></span></span></span><br> <span style="font-size:12pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:10.0pt"><span arial="" style="font-family:"><span style="color:black">Conclusion</span></span></span></b><b><span style="font-size:10.0pt"><span style="color:black">: </span></span></b><span style="font-size:10.0pt"><span style="color:black">Compound<b> 5</b></span></span><span style="font-size:10.0pt"><span style="color:black"> can be quantitatively radiolabeled </span></span><span style="font-size:10.0pt"><span style="color:black">with </span></span><i><span style="font-size:10.0pt"><span style="color:black">fac</span></span></i><span style="font-size:10.0pt"><span style="color:black">-[^99mTc(CO)₃(H₂O)₃]⁺&nbsp;resulting in the radiotracer (^99mTc(CO)₃-[<b>5</b>]). The initial </span></span><span style="font-size:10.0pt"><span style="color:black">radiochemical purity of this radiotracer is approximately 95%; however, its stability decreases over time. </span></span>^{<span style="font-size:10.0pt"><span style="color:black">99m</span></span>}<span style="font-size:10.0pt"><span style="color:black">Tc(CO)₃-[<b>5</b>] recognizes the&nbsp; 5-HT₇R on the surface of U87-MG cells and binds to this receptor with moderate affinity.<i></i></span></span></span></span></span><br> &nbsp; تصویربرداری, SPECT, U87-MG, گیرنده سروتونین,گلیوبلاستوما imaging, SPECT, U87-MG, serotonin receptor, glioblastoma 14 25 http://jmums.mazums.ac.ir/browse.php?a_code=A-10-17924-1&slc_lang=fa&sid=1 Sajjad Molavipordanjani سجاد مولوی پردنجانی Sajjad.molavi@gmail.com 1003194753284600175032 1003194753284600175032 Yes Assistant Professor, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran استادیار، مرکز تحقیقات علوم دارویی، دانشگاه علوم پزشکی مازندران، ساری، ایران