18F-labeled BBN-RGD heterodimer for prostate cancer imaging.

Unlabelled: Both bombesin (BBN) analogs and cyclic RGD peptides have been suitably radiolabeled for prostate cancer imaging. However, the limited expression of gastrin-releasing peptide receptor (GRPR) and integrin alpha(v)beta(3) as well as unfavorable in vivo kinetics limited further applications of these imaging agents. We hypothesize that a peptide ligand recognizing both GRPR and integrin will be advantageous because of its dual-receptor-targeting ability.

(68)Ga-labeled multimeric RGD peptides for microPET imaging of integrin alpha(v)beta (3) expression.

Purpose: We and others have reported that (18)F- and (64)Cu-labeled arginine-glycine-aspartate (RGD) peptides allow positron emission tomography (PET) quantification of integrin alpha(v)beta(3) expression in vivo. However, clinical translation of these radiotracers is partially hindered by the necessity of cyclotron facility to produce the PET isotopes. Generator-based PET isotope (68)Ga, with a half-life of 68 min and 89% positron emission, deserves special attention because of its independence of an onsite cyclotron.

The synthesis of 18F-FDS and its potential application in molecular imaging.

Purpose: 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) is the most commonly used positron emission tomography (PET) tracer for oncological and neurological imaging, but it has limitations on detecting tumor or inflammation in brain gray matter. In this study, we describe the development of 2-deoxy-2-[(18)F]fluorosorbitol ((18)F-FDS) and its possible application in lesion detection around brain area.

Procedures: (18)F-FDS was obtained by reduction of FDG using NaBH(4) (81 +/- 4% yield in 30 min).

Click chemistry for (18)F-labeling of RGD peptides and microPET imaging of tumor integrin alphavbeta3 expression.

The cell adhesion molecule integrin alpha vbeta 3 plays a key role in tumor angiogenesis and metastasis. A series of (18)F-labeled RGD peptides have been developed for PET of integrin expression based on primary amine reactive prosthetic groups. In this study, we report the use of the Cu(I)-catalyzed Huisgen cycloaddition, also known as a click reaction, to label RGD peptides with (18)F by forming 1,2,3-triazoles.

Dual-function probe for PET and near-infrared fluorescence imaging of tumor vasculature.

Unlabelled: To date, the in vivo imaging of quantum dots (QDs) has been mostly qualitative or semiquantitative. The development of a dual-function PET/near-infrared fluorescence (NIRF) probe can allow for accurate assessment of the pharmacokinetics and tumor-targeting efficacy of QDs.

Methods: A QD with an amine-functionalized surface was modified with RGD peptides and 1,4,7,10-tetraazacyclodocecane-N,N',N'',N'''-tetraacetic acid (DOTA) chelators for integrin alpha(v)beta(3)-targeted PET/NIRF imaging.

64Cu-Labeled triphenylphosphonium and triphenylarsonium cations as highly tumor-selective imaging agents.

This report presents synthesis and evaluation of the 64Cu-labeled triphenylphosphonium (TPP) cations as new radiotracers for imaging tumors by positron emission tomography. Biodistribution properties of 64Cu-L1, 64Cu-L2, 64Cu-L3, and 99mTc-Sestamibi were evaluated in athymic nude mice bearing U87MG human glioma xenografts. The most striking difference is that 64Cu-L1, 64Cu-L2, and 64Cu-L3 have much lower heart uptake (<0.

microPET of tumor integrin alphavbeta3 expression using 18F-labeled PEGylated tetrameric RGD peptide (18F-FPRGD4).

Unlabelled: In vivo imaging of alpha(v)beta(3) expression has important diagnostic and therapeutic applications. Multimeric cyclic RGD peptides are capable of improving the integrin alpha(v)beta(3)-binding affinity due to the polyvalency effect. Here we report an example of (18)F-labeled tetrameric RGD peptide for PET of alpha(v)beta(3) expression in both xenograft and spontaneous tumor models.

A new PET tracer specific for vascular endothelial growth factor receptor 2.

Purpose: Noninvasive positron emission tomography (PET) imaging of vascular endothelial growth factor receptor 2 (VEGFR-2) expression could be a valuable tool for evaluation of patients with a variety of malignancies, and particularly for monitoring those undergoing antiangiogenic therapies that block VEGF/VEGFR-2 function. The aim of this study was to develop a VEGFR-2-specific PET tracer.

Methods: The D63AE64AE67A mutant of VEGF(121) (VEGF(DEE)) was generated by recombinant DNA technology.

Semiconductor quantum dots for in vivo imaging.

Quantum dots play an important role in the in vitro, ex vivo, and in vivo optical imaging. Dramatic improvements have been achieved in the aspect of surface modification, biocompatibility, and targeting specificity, which had significant impact on the in vivo applications of quantum dots. This review summarizes the recent advances of quantum dots for in vivo imaging using both non-specific and targeted approaches.

Quantitative radioimmunoPET imaging of EphA2 in tumor-bearing mice.

Purpose: EphA2 receptor tyrosine kinase is significantly overexpressed in a wide variety of cancer types. High EphA2 expression has been correlated with increased metastatic potential and poor patient survival. Although many recent reports have focused on blocking the EphA2 signaling pathway in cancer, the in vivo imaging of EphA2 has not yet been investigated.

(64)Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor alpha(v)beta(3) integrin expression.

Unlabelled: Integrin alpha(v)beta(3) plays a critical role in tumor angiogenesis and metastasis. Suitably radiolabeled cyclic arginine-glycine-aspartic (RGD) peptides can be used for noninvasive imaging of alpha(v)beta(3) expression and targeted radionuclide therapy. In this study, we developed (64)Cu-labeled multimeric RGD peptides, E{E[c(RGDyK)](2)}(2) (RGD tetramer) and E(E{E[c(RGDyK)](2)}(2))(2) (RGD octamer), for PET imaging of tumor integrin alpha(v)beta(3) expression.

PET imaging of acute and chronic inflammation in living mice.

Purpose: In this study, we evaluated the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced acute and chronic inflammation in living mice by PET imaging of TNF-alpha and integrin alpha(v)beta(3) expression.

Methods: TPA was topically applied to the right ear of BALB/c mice every other day to create the inflammation model. (64)Cu-DOTA-etanercept and (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) were used for PET imaging of TNF-alpha and integrin alpha(v)beta(3) expression in both acute and chronic inflammation.

Are quantum dots ready for in vivo imaging in human subjects?

Nanotechnology has the potential to profoundly transform the nature of cancer diagnosis and cancer patient management in the future. Over the past decade, quantum dots (QDs) have become one of the fastest growing areas of research in nanotechnology. QDs are fluorescent semiconductor nanoparticles suitable for multiplexed in vitro and in vivo imaging.

Enantioselective fluorescent recognition of chiral acids by cyclohexane-1,2-diamine-based bisbinaphthyl molecules.

The cyclohexane-1,2-diamine-based bisbinaphthyl macrocycles (S)-/(R)-5 and their cyclic and acyclic analogues are synthesized. The interactions of these compounds with various chiral acids are studied. Compounds (S)-/(R)-5 exhibit highly enantioselective fluorescent responses and high fluorescent sensitivity toward alpha-hydroxycarboxylic acids and N-protected amino acids.

Chiral macrocycle-catalyzed highly enantioselective phenylacetylene addition to aliphatic and vinyl aldehydes.

The 1,1'-binaphthyl macrocycle (S)-2 is found to be an excellent catalyst for the alkyne addition to aldehydes. In the presence of (S)-2 (20 mol %) and Me2Zn (2 equiv) in THF at room temperature, the addition of phenylacetylene to linear or branched aliphatic aldehydes and vinyl aldehydes gave various propargylic alcohols with 89-96% ee.

18F-labeled mini-PEG spacered RGD dimer (18F-FPRGD2): synthesis and microPET imaging of alphavbeta3 integrin expression.

Purpose: We have previously reported that (18)F-FB-E[c(RGDyK)](2) ((18)F-FRGD2) allows quantitative PET imaging of integrin alpha(v)beta(3) expression. However, the potential clinical translation was hampered by the relatively low radiochemical yield. The goal of this study was to improve the radiolabeling yield, without compromising the tumor targeting efficiency and in vivo kinetics, by incorporating a hydrophilic bifunctional mini-PEG spacer.

Recombinant AAV-mediated HSVtk gene transfer with direct intratumoral injections and Tet-On regulation for implanted human breast cancer.

Background: HSVtk/ganciclovir (GCV) gene therapy has been extensively studied in tumors and relies largely on the gene expression of HSVtk. Most studies, however, have failed to demonstrate any significant benefit of a controlled gene expression strategy in cancer treatment. The Tet-On system is commonly used to regulate gene expression following Dox induction.

[The construction of recombinant AAV vector expressing HSVtk gene controlled by Tet-On and the detection of its activity].

In order to investigate the application of recombinant adeno-associated virus (rAAV) vector containing Tet regulation system and HSVtk gene in cancer gene therapy, pAAV/TRE/HSVtk/Tet-On was constructed and identified with PCR and restriction enzyme digestion. Packaging cells HEK293 were cotransfected with plasmids pAAV/TRE/HSVtk/Tet-On, pAAV-RC and pAAV-helper to produce infectious rAAV, and CsCl2 densitygradient centrifugation method was performed for purification and concentration of rAAV. The viruses were then transduced into MCF-7 cells.

Enantioselective fluorescent recognition of a soluble "supported" chiral acid: toward a new method for chiral catalyst screening.

The long-chain aliphatic-group-substituted mandelic acid 3c, which is soluble only in THF and insoluble in water and many polar/nonpolar organic solvents, has been synthesized. This unique solubility allows 3c to be easily isolated from reaction mixtures and makes it potentially useful for catalyst screening. The fluorescent sensors (R)- and (S)-1 can be used to determine the ees of various samples of 3c generated from a series of catalyst screening experiments.

Macrocyclic bisbinaphthyl fluorophores and their acyclic analogues: signal amplification and chiral recognition.

A series of optically active macrocyclic and acyclic bisbinaphthyls have been synthesized and characterized. The structure of one of the bisbinaphthyl macrocycles has been established by a single-crystal X-ray analysis. The UV and fluorescence spectra of these chiral compounds in various solvents and at different concentrations are studied.

BINOL-Salen-catalyzed highly enantioselective alkyne additions to aromatic aldehydes.

[structure: see text] The BINOL-Salen compound (-)-1 can catalyze the addition of both aryl- and alkylalkynes to aromatic aldehydes at room temperature with high enantioselectivity (86-97% ee). The conditions for this catalytic process are both mild and simple. Unlike most other BINOL-based catalysts, using ligand (-)-1 not only avoids heating or cooling but also does not require the addition of Ti(O(i)Pr)(4).