Synthesis of a stabilized 177Lu-siRNA complex and evaluation of its stability and RNAi activity

Nuclear Medicine Communications
Mojtaba FathiMohammad Ghannadi Maragheh

Abstract

Serum and intracellular instability limits the therapeutic applications of short interfering RNA (siRNA) as a radiopharmaceutical. Chemical modifications like phosphorothioate (PS) substitution and 2'-O-methoxy (2'-O-Me) modifications could eliminate such limitations. In this study, the effects of PS and 2'-O-Me modifications at the backbone of siRNA on serum stability and RNA interference activity were investigated. Fully PS and 2'-O-Me-modified type 1 insulin-like growth factor receptor (IGF-1R) siRNA was radiolabeled with lutetium-177 ((177)Lu) through p-SCN-Bn-DTPA as a chelator. After purification with Vivaspin and PD-10 columns, the radiolabs were examined for stability in serum by instant thin-layer chromatography and polyacrylamide gel electrophoresis. The level of IGF-1R in response to the modified and labeled IGF-1R siRNA was examined using RT-PCR and ELISA assay in colon cancer cells. The effects of such siRNA on the prevention of proliferation of colon cancer cells and its apoptosis were investigated using MTT assay and Annexin-V/propidium iodide double staining, respectively. Cellular accumulation quantities of the labeled and modified IGF-1R siRNA were determined using a γ-counter by taking advantage of (177)Lu as...Continue Reading

References

Jul 2, 2003·Biochemistry·Dwaine A BraaschDavid R Corey
Feb 26, 2004·Bioorganic & Medicinal Chemistry Letters·Dwaine A BraaschDavid R Corey
Oct 1, 2004·Anti-cancer Drugs·Ann Mari SaeternBaldur Sveinbjørnsson
Apr 7, 2006·Biochemical and Biophysical Research Communications·Sorim ChoungYoung-Chul Choi
May 23, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Femke M van de WaterRosalinde Masereeuw
Jun 15, 2007·European Journal of Nuclear Medicine and Molecular Imaging·Glenn FluxMichael Lassmann
Sep 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Derek W BartlettMark E Davis
Jul 9, 2008·Biochemistry. Biokhimii︠a︡·N V Zhukov, S A Tjulandin
Sep 16, 2008·European Journal of Immunology·Andrej ManteiAlexander Scheffold
Jul 18, 2009·Archives of Medical Research·Kamal YavariMohammad Hosein Babaei
Aug 4, 2009·Nuclear Medicine and Biology·Eftychia KoumarianouSpyridon C Archimandritis
Dec 17, 2009·Acta Oncologica·Kamal YavariHamid Reza Mirzaei
May 21, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Lei KangXiao Jie Xu
Nov 3, 2010·Clinics in Colon and Rectal Surgery·Fatima A Haggar, Robin P Boushey
Dec 31, 2010·The Journal of Investigative Dermatology·Robyn P HickersonRoger L Kaspar
Sep 23, 2014·Chembiochem : a European Journal of Chemical Biology·Yukiko KamiyaHiroyuki Asanuma

❮ Previous
Next ❯

Citations

Jan 10, 2016·Nuclear Medicine and Biology·Marlies GijsAndré Luxen
Jan 4, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M KhodaeiM Fathi

❮ Previous
Next ❯

Methods Mentioned

BETA
chemical modification
electrophoresis
flow cytometry
transfection
ELISA
flow

Software Mentioned

SPSS
BLAST

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.