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Because of our interest in developing new hybrid peptide radioconjugates with suitable biochemical properties for multiple-receptors targeting properties that are overexpressed on many human cancers especially ovarian cancer, we have synthesized 68Ga-NODAGA-MUC1 and 68Ga-NODAGA-MUC1-FA hybrid peptide conjugates using a straightforward and one-step simple reaction. Radiochemical yields were found to be higher than 95% (decay corrected), with a total synthesis time of less than 20 min. Radiochemical purities were always higher than 95% without HPLC purification. In vitro studies on KB cancer cells showed that substantial amounts of the radioconjugates were associated with cell fractions and held great affinities and specificities toward the KB cell line. In vivo characterization in normal female Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary system. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for 68Ga-NODAGA-MUC1-FA hybrid peptide conjugate compared to the 68Ga-NODAGA-MUC1 peptide monomeric counterpart. The uptake in the tumors was blocked by the excess injection of hybrid peptide, suggesting a receptor-mediated process. These results demonstrate that 68Ga-NODAGA-MUC1-FA hybrid peptide conjugate may be useful as a molecular probe for early detection and staging of folate and MUC1 receptor-positive cancers such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment.

Curcumin (Diferuloylmethane) is a natural product extracted from the root of Curcuma longa. 5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone, the piperidone analogue of curcumin (PAC), was one of the analogues that, demonstrated potential anticancer effects against breast and colon cancers compared with native curcumin. A simple, accurate, and rapid isocratic reverse phase high performance liquid chromatography (HPLC) analytical method utilizing UV detection was developed and validated for the determination of PAC utilizing C

Curcumin (Diferuloylmethane) is a natural product extracted from the root of Curcuma longa. 5-Bis (4-hydroxy-3-methoxybenzylidene)-Nmethyl-4-piperidone, the piperidone analogue of curcumin (PAC), was one of the analogues that, demonstrated potential anticancer effects against breast and colon cancers compared with native curcumin. A simple, accurate, and rapid isocratic reverse phase HPLC analytical method utilizing UV detection was developed and validated for the determination of PAC. A C18 column (4.6 mm × 150 mm, 3 μm spherical particles) was used with acetonitrile: 5% acetic acid (50:50, v/v) as a mobile phase at a flow rate of 1.0 mL/min and monitored at 392 nm. The run time was 7 min. Chromatogram showed a peak of PAC at retention time of 5.8 ± 0.92 min. The method was validated for linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. Linear relationship (r>0.99) was observed between AUP of PAC and the corresponding concentrations over 100-10000 µg/mL. The mean linear regression equation was Y=52.42 X - 2562.7 for PAC. The LOQ of this assay was 3.9 ng/mL with corresponding relative standard deviation of 4.8 and 4.0%. The LOD was 13.1 ng/mL at a signal-to-noise ratio of >3.

Cancer is a broad term used to describe different types of tumors affecting various parts of the human body. The resistance to multiple therapeutic agents, toxicity to healthy tissues, and lack of effective therapies obligate scientists to keep looking for new agents. Curcumin (diferuloylmethane) is a natural product. It has been reported that curcumin has anti-inflammatory, anti-diabetic, and anti-cancer effects. However, clinical use of curcumin is limited due to its poor aqueous solubility. Recently, a curcumin analogue, 5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone of curcumin (PAC), was synthesized to overcome this limitation. This compound showed significantly higher anticancer activity on breast cancer cell lines and colon cancer cell lines as compared to native curcumin. However, aqueous solubility of this new chemical compound limited its use and application. Liposomes were found to be the most promising system to use to overcome aqueous solubility and delivery limitations. Liposomes are a self-assembly of phospholipid molecules. They are biodegradable, biocompatible, and nontoxic carrier systems. These features make liposomes an ideal carrier system for anticancer agents. In this study liposomes were utilized to overcome PAC limitations. This project was designed to develop liposomal delivery system for PAC for cancer treatment and evaluate the anti-cancer properties of this system. Liposomal PAC formulae were prepared by the film hydration method and were optimized by adding hydroxypropyl-beta-cyclodextrin (HPβCD) and characterized in term of particle size, entrapment efficiency, release profile and cytotoxic activity. Liposomes with an average size below 150 nm and zwitterionic charge were obtained. Indeed, no major differences were seen in particle size and surface charge. However, HPβCD inclusion gave satisfied incorporation capacity reaching 68.1%. In addition, HPβCD inclusion in the liposomes resulted in increased in vitro release rate compared to conventional liposomes. On colon cancer cells, Annexin V/PI- Flow Cytometery cytotoxicity results revealed that the PAC-loaded HPβ-cyclodextrin liposomes trigger apoptosis by 75% in response (10 µM), whereas it was only 43% in response to the same concentration of PAC conventional liposomes, which confirmed their potential anti-cancer activity. On breast cancer cells, Annexin V/PI- Flow Cytometery cytotoxicity results showed that while PAC conventional liposomes have only minor cytotoxic effect (22-25%), PAC-loaded HPβCD liposomes induced 53% and 70% apoptosis in response to 5 µM and 10 µM, respectively. The cytotoxicity of PAC-loaded HPβ-cyclodextrin liposomes was more pronounced than PAC conventional liposomes in both cells, suggesting the benefits of using HPβ-cyclodextrin. Therefore, PAC-loaded HPβ-cyclodextrin liposomes indicate significant potential as delivery vehicles for the treatment of cancers.