Radiolabeling, biodistribution and gamma scintigraphy of noscapine hydrochloride in normal and polycystic ovary induced rats

Abstract

BackgroundNoscapine, an alkaloid from Papaver somniferum, widely used as an antitussive, is being clinically studied in the treatment of polycystic ovary syndrome (PCOS) and a few other cancers primarily because of its anti-angiogenesis properties. With the advent of diverse application of noscapine, we sought to determine whether the radiolabeling method can be useful in studying uptake and kinetics of the molecule in-vivo. Specific objectives of this study were to radiolabel noscapine with Technetium-99m (Tc-99m), to determine its organ biodistribution in rat model and study its uptake kinetics in PCOS model.MethodsA method for radiolabeling noscapine with Tc-99m was standardized using stannous reduction method and its in vitro and in vivo stability parameters were studied. The radiopharmaceutical was also evaluated for blood kinetics and biodistribution profile. An animal model of PCOS was created by using antiprogesterone RU486 and uptake of 99mTc-noscapine in normal and PCOS ovaries was compared using gamma scintigraphy.ResultsNoscapine hydrochloride was successfully radiolabeled with Tc-99m with high labeling efficiency and in vitro stability. Most of the blood clearance of the drug (80%) took place in first hour after intravascular injection with maximum accumulation being observed in liver, spleen, kidney followed by the ovary. At 4 hours post injection, radiolabeled complex accumulation doubled in PCOS ovaries in rats (0.9 ± 0.03% ID/whole organ) compared to normal cyclic rats (0.53 ± 0.01% ID/whole organ). This observation was further strengthened by scintigraphic images of rats taken at different time intervals (1 h, 2 h, 4 h, and 24 h) where SPECT images suggested discrete accumulation in the PCOS ovaries.ConclusionThrough our study we report direct radiolabeling of noscapine and its biodistribution in various organs and specific uptake in PCOS that may show its utility for imaging ovarian pathology. The increased ovarian uptake in PCOS may be related to its receptor binding suggesting possible role of 99mTc-noscapine in PCOS diagnostics and therapeutics.

Role of the PI3K-Akt Signaling Pathway in the Pathogenesis of Polycystic Ovary Syndrome

“…From another point of view, Priyadarshani et al 14 reported successful action of noscapine in the amelioration of PCOS. Noscapine is a plant alkaloid that serves as a cough suppressant.…”

Quantitative Whole Body Biodistribution of Fluorescent-Labeled Agents by Non-Invasive Tomographic Imaging

“…Preclinical biodistribution and pharmacokinetics data for investigational agents are routinely obtained in animal studies using radiolabeled materials [6] . Many of these studies employ post-mortem scintillation counting of the labeled radioactivity in excised organs and tissues [7] , [8] . Additional understanding of the kinetic changes in biodistribution has generally required either the sacrifice of multiple animals at multiple time points or the use of non-invasive nuclear imaging techniques.…”

Anticancer Activity of Papaver Somniferum

“…Current studies show that alkaloids obtained from Papaver species could not only be used as analgesic or sedative but also in other areas such as cancer treatment [12]. P. somniferum L. alkaloids that show promise in cancer treatment include noscapine, which interacts with α-tubulin and has anticancer and antiangiogenetic properties [13,14]; codeinone, an oxidative product of codeine which has apoptotic effects through fragmentation of DNA [15]; morphine, which shows anticancer activities by inhibiting NF-κB; and (-)-3-acetyl-6β-(acetylthio)-N-(cyclopropyl-methyl)-normorphine (KT-90), a derivative of morphine [16]. To the best of our knowledge, pharmacological effects of P. somniferum L. extracts on HT29, HeLa, C6 cancer cell lines and Vero normal cell lines have not been investigated in detail.…”