title: Platelet-12 lipoxygenase targeting via a newly synthesized curcumin derivative radiolabeled with technetium-99m.
abstract: BACKGROUND
  One of the most popular techniques for cancer detection is the nuclear medicine technique. The present research focuses on Platelet-12-lipoxygenase (P-12-LOX) as a promising target for treating and radio-imaging tumor tissues. Curcumin was reported to inhibit this enzyme via binding to its active site.
  
  
  RESULTS
  A novel curcumin derivative was successfully synthesized and characterized with yield of 74%. It was radiolabeled with the diagnostic radioisotope technetium-99m with 84% radiochemical yield and in vitro stability up to 6 h. The biodistribution studies in tumor bearing mice confirmed the high affinity predicted by the docking results with a free binding energy value of (ΔG -50.10 kcal/mol) and affinity (13.64 pki) showing high accumulation in solid tumor with target/non-target ratio >6.
  
  
  CONCLUSIONS
  The newly synthesized curcumin derivative, as a result of a computational study on platelet-12 lipoxygenase, showed its excellent free binding energy (∆G -50.10 kcal/mol) and high affinity (13.64 pKi). It could be an excellent radio-imaging agent that targeting tumor cells via targeting of P-12-LOX.Graphical abstractThis novel curcumin derivative was successfully synthesized and radiolabeled with technetium-99m and biologically evaluated in tumor bearing mice that showed high accumulation in solid tumor with target/non-target ratio >6 confirming the affinity predicted by the docking results. Predicted binding mode ofanew curcumin derivative in complex with 12-LOX active site.bCurcumin itself in the 12-LOX active site biological distribution of99mTc-curcumin derivative complex in solid tumor bearing Albino mice.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451 Saudi Arabia.
authors.forename: Reem Ibrahim
authors.initials: RI
authors.lastname: Al-Wabli
authors.affiliation: Radioactive Isotopes and Generator Department, Hot Labs Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
authors.forename: Tamer Mostafa Mohamed Hafez
authors.initials: TM
authors.lastname: Sakr
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo, 11795 Egypt.
authors.forename: Mohammed Abdou
authors.initials: MA
authors.lastname: Khedr
authors.affiliation: Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
authors.forename: Adly Abdallah
authors.initials: AA
authors.lastname: Selim
authors.affiliation: Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
authors.forename: Mohamed Abd El-Motaleb Abd
authors.initials: MA
authors.lastname: El-Rahman
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo, 11795 Egypt.
authors.forename: Wafaa Abdou
authors.initials: WA
authors.lastname: Zaghary
keywords: Cancer imaging; Curcumin; Docking; Enzyme targeting; Platelet-12 lipoxygenase; Technetium-99m