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Herein, we report the development of an 18 F-labeled, activity-based small-molecule probe targeting the cancer-associated serine hydrolase NCEH1. We undertook a focused medicinal chemistry campaign to simultaneously preserve potent and specific NCEH1 labeling in live cells and animals, while permitting facile 18 F radionuclide incorporation required for PET imaging. The resulting molecule, [18 F]JW199, labels active NCEH1 in live cells at nanomolar concentrations and greater than 1000-fold selectivity relative to other serine hydrolases. [18 F]JW199 displays rapid, NCEH1-dependent accumulation in mouse tissues. Finally, we demonstrate that [18 F]JW199 labels aggressive cancer tumor cells in vivo, which uncovered localized NCEH1 activity at the leading edge of triple-negative breast cancer tumors, suggesting roles for NCEH1 in tumor aggressiveness and metastasis.

In a low-resource setting, an ideal disease diagnostic modality is an eye visualization assay that can be performed in minutes by untrained personnel. This paper reports the development of a self-catalytic colorimetric assay to detect the existence of cervical cancer cells by naked eye. The assay consists of a target specific initiator/catalyst, an acid self-catalytic system, and a pH indicator solution. By taking the advantage that trace amount of nucleus staining molecule, hemalum, can function as the initiator, a stained cervical cancer cell with an enlarged nucleus can initiate the self-catalytic reaction in a defined reaction condition to produce a significant amount of acid, which leads to a color change of a pH indicator solution, thereby indicating the presence of the cancer cell. Amplification of at least a trillion fold was achieved within 1.5 min. Due to the minimum engagement of instruments, simplicity and low cost, the assay is a potential tool in clinical to function as a “yes/no” check to facilitate quick decisions for cervical cancer screening. By alternating the method whereby the initiator is associated with the target, the assay can be expanded to screen and detect protein or nucleic acid based biomarkers related to other epidemic diseases in the resource-limited settings.

Aim: The authors have investigated the usefulness of in vivo chemical exchange saturation transfer MRI for detecting gliomas using a dual-modality imaging contrast agent. Materials & methods: A paramagnetic chemical exchange saturation transfer MRI contrast agent, Eu-1,4,7,10-tetraazacclododecane-1,4,7,10-tetraacetic acid-Gly4 and a fluorescent agent, DyLight® 680, were conjugated to a generation 5 polyamidoamine dendrimer to create the dual-modality, nano-sized imaging contrast agent. Results: The agent was detected with in vivo chemical exchange saturation transfer MRI in an U87 glioma model. These results were validated using in vivo and ex vivo fluorescence imaging. Conclusion: This study demonstrated the merits of using a nano-sized imaging contrast agent for detecting gliomas and using a dual-modality agent for detecting gliomas at different spatial scales. Original submitted 9 January 2012; Revised submitted 18 April 2012; Published online 14 August 2012

Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that effect gene regulation. To know the interaction of aliphatic cap groups with HDACs, cyclic tetrapeptide and bicyclic peptide disulfide hybrids were synthesized without aromatic ring in their macrocyclic framework. Benzene ring of l -Phe in chlamydocin was replaced with several aliphatic amino acids and also a fused bicyclic tetrapeptide was synthesized by ring closing metathesis using Grubb’s first generation catalyst. The inhibitory activities of the cyclic peptides against histone deacetylase enzymes were evaluated, which demonstrated most of them are interesting candidates as anticancer agents.

[60]-Fullerene functionalized amino acids with 4–6 methylene spacers from α-carbon to the nitrogen atom of fulleropyrolidine and corresponding multifullerene peptides have been synthesized.