Many solid tumors contain an overabundance of phospholipid ethers relative to normal cells. Capitalizing on this difference, we created cancer-targeted alkylphosphocholine (APC) analogs through structure-activity analyses. Depending on the iodine isotope used, radioiodinated APC analog CLR1404 was used as either a positron emission tomography (PET) imaging (124I) or molecular radiotherapeutic (131I) agent. CLR1404 analogs displayed prolonged tumor-selective retention in 55 in vivo rodent and human cancer and cancer stem cell models. 131I-CLR1404 also displayed efficacy (tumor growth suppression and survival extension) in a wide range of human tumor xenograft models. Human PET/CT (computed tomography) and SPECT (single-photon emission computed tomography)/CT imaging in advanced-cancer patients with 124I-CLR1404 or 131I-CLR1404, respectively, demonstrated selective uptake and prolonged retention in both primary and metastatic malignant tumors. Combined application of these chemically identical APC-based radioisosteres will enable personalized dual modality cancer therapy of using molecular 124I-CLR1404 tumor imaging for planning 131I-CLR1404 therapy.

In this experiment students prepare nickel nanowires using a template synthesis technique and characterize their properties. Electrodeposition of nickel to fill the 200-nm diameter pores of a commercially-available alumina filtration membrane is accomplished using a nickel salt solution and a AA battery. The nanowires, which are ~200 nm in diameter and up to ~50 μm in length, can be liberated from the membrane by dissolving the alumina template with sodium hydroxide. Suspensions of nanowires on a microscope slide can be observed using a common optical microscope. The alignment and movement of the magnetic nanowires can be controlled using magnets. This experiment is appropriate in introductory college chemistry courses and in upper-level physical and inorganic chemistry courses. The experiment provides students with a hands-on laboratory experience in nanotechnology, while illustrating fundamental ideas from a variety of areas, including electrochemistry, magnetism, and materials science.

Aberrations in the phosphatidylinositide-3-kinase (PI3K) signaling pathway play a key role in the pathogenesis of numerous cancers by altering cellular growth, metabolism, proliferation, and apoptosis (1). Mutations in the catalytic domain of PI3K that generate a dominantly active kinase are commonly found in human colorectal cancers and have been thought to drive tumor progression, but not initiation (2). However, the effects of constitutively activated PI3K upon the intestinal mucosa have not been previously studied in animal models. Here, we demonstrate that the expression of a dominantly active form of the PI3K protein in the mouse intestine results in hyperplasia and advanced neoplasia. Mice expressing constitutively active PI3K in the epithelial cells of the distal small bowel and colon rapidly developed invasive adenocarcinomas in the colon that spread into the mesentery and adjacent organs. The histological characteristics of these tumors were strikingly similar to invasive mucinous colon cancers in humans. Interestingly, these tumors formed without a benign polypoid intermediary, consistent with the lack of aberrant WNT signaling observed. Together, our findings indicate a non-canonical mechanism of colon tumor initiation that is mediated through activation of PI3K. This unique model has the potential to further our understanding of human disease and facilitate the development of therapeutics through pharmacologic screening and biomarker identification.

Background 5-ALA induced tumor fluorescence aids brain tumor resections but is not approved for routine use in the United States. We developed and describe testing of two novel fluorescent, cancer-selective alkylphosphocholine analogs, CLR1501 (green) and CLR1502 (near-infrared), in a proof-of-principle study for fluorescence-guided glioma surgery. Objective To demonstrate CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and compare tumor (T) to normal brain (N) fluorescence ratios with 5-ALA. Methods CLR1501, CLR1502, 5-ALA were administered to mice with MRI-verified orthotopic U251 GBM and GSC-derived xenografts. Harvested brains were imaged using confocal microscopy (CLR1501), IVIS Spectrum imaging system (CLR1501, CLR1502, and 5-ALA), or Fluobeam near-infrared fluorescence imaging system (CLR1502). Imaging and quantitative analysis of T:N fluorescence ratios were performed. Results Excitation/emission peaks are 500/517nm for CLR1501, and 760/778nm for CLR1502. The observed T:N ratio of CLR1502 (9.28±1.08) was significantly higher (p<0.01) than CLR1501 (3.51±0.44 on confocal imaging; 7.23±1.63 on IVIS imaging) and 5-ALA (4.81±0.92). Near-infrared Fluobeam CLR1502 imaging in a mouse xenograft model demonstrated high contrast tumor visualization compatible with surgical applications. Conclusion CLR1501 (green) and CLR1502 (near infrared) are novel tumor-selective fluorescent agents for discriminating tumor from normal brain. CLR1501 exhibits a tumor to brain fluorescence ratio similar to 5-ALA, whereas CLR1502 has a superior tumor to brain fluorescence ratio. This study demonstrates the potential use of CLR1501 and CLR1502 in fluorescence-guided tumor surgery.