Organometalloid compositions of silicon and boron permit rapid, high-yielding, one-step radiolabeling of a covalently linked protein ligand (biotin) under aqueous conditions to give the corresponding alkyltetrafluorosilicates and aryltrifluoroborate salts. Biotin was chosen as a test ligand for protein targeting because of its quantitative interaction with avidin, which in turn allowed us to calculate fluoridation yields that approach 80-100%. The silicate was found to be moderately stable to hydrolysis, whereas the borate appears to be so stable that its hydrolytic decomposition was not readily measured. With the stability of both compounds ascertained, this work describes a novel and robust radiolabeling method that may find use in the development of positron emission tomography radiopharmaceuticals.

Whereas electron withdrawing substituents retard the rate of aryltrifluoroborate solvolysis, electron-donating groups enhance it. Herein is presented a Hammett analysis of the solvolytic lability of aryltrifluoroborates where log(k(solv)) values correlate to sigma values with a rho value of approximately -1. This work provides a predictable rubric for tuning the reactivity of boron for several uses including (18)F-labeled PET reagents and has mechanistic implications for ArBF(3)-enhanced ligandless metal-mediated cross coupling reactions with aryltrifluoroborates.

The use of a boronic ester as a captor of aqueous [(18)F]-fluoride has been previously suggested as a means of labeling biomolecules in one step for positron emission tomography (PET) imaging. For this approach to be seriously considered, the [(18)F]-labeled trifluoroborate should be humorally stable such that it neither leaches free [(18)F]-fluoride to the bone nor accumulates therein. Herein, we have synthesized a biotinylated boronic ester that is converted to the corresponding trifluoroborate salt in the presence of aqueous [(18)F]-fluoride. In keeping with its in vitro aqueous kinetic stability at pH 7.5, the trifluoroborate appears to clear in vivo quite rapidly to the bladder as the stable trifluoroborate salt with no detectable leaching of free [(18)F]-fluoride to the bone. When this labeled biotin is preincubated with avidin, the pharmacokinetic clearance of the resulting complex is visibly altered. This work validates initial claims that boronic esters are potentially useful as readily labeled precursors to [(18)F]-PET reagents.

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We combine a novel boronate trap for F− with a near-infrared fluorophore into a single molecule. Attachment to targeting ligands enables localization by positron emission tomography (PET) and near-infrared fluorescence (NIRF). Our first application of this generic tag is to label Lymphoseek (tilmanocept), an agent designed for receptor-specific sentinel lymph node (SLN) mapping. The new conjugate incorporates 18F− in a single, aqueous step, targets mouse SLN rapidly (1 h) with reduced distal lymph node accumulation, permits PET or scintigraphic imaging of SLN, and enables NIRF-guided excision and histological verification even after 18F decay. This embodiment is superior to current SLN mapping agents such as nontargeted [99mTc]sulfur colloids and Isosulfan Blue, as well as the phase III targeted ligand [99mTc]SPECT Lymphoseek counterpart, species that are visible by SPECT or visible absorbance separately. Facile incorporation of 18F into a NIRF probe should promote many synergistic PET and NIRF combinations.

Light provides an effective means of willfully inducing reactivity to study kinetically complex biological processes and to localize drug action for photodynamic therapy. In most cases, photoactivation is a consequence of irreversible photodeprotection to cleanly unleash the biologically active molecule of interest. Examples include substrates such as ATP, 1a GABA, 1b estradiol, 1c N-ras-peptides, 1d and an mRNA target for ribozymes, 1e,f allosteric ligands such as cAMP 1g and inositol triphosphate, 1h toxins such as ricin, 1i antibodies to protein-A, 1j and enzymes such as thrombin 1k,l and RNaseA. 1m

Site-specific RNA cleavage has received considerable attention over the years. Directed synthesis to append imidazoles or amines or both to oligonucleotides to target specific RNA cleavage represents an exciting avenue of research. However, to date catalysis by such synthetic constructs, particularly in terms of turnover, has been difficult to observe. This is the first report of a truly catalytic M2+-independent DNAzyme synthetically modified with imidazoles and cationic amines that would seem to mimic RNaseA. This work now demonstrates how synthetic organic chemistry, when merged with combinatorial selection, can result in a new class of DNAzymes that meets the ongoing synthetic challenges for developing relatively small biomimetic catalysts.

OBJECTIVE The purpose of this article is to summarize advances in PET fluorescence resolution, agent design, and preclinical imaging that make a growing case for clinical PET fluorescence imaging. CONCLUSION Existing SPECT, PET, fluorescence, and MRI contrast imaging techniques are already deeply integrated into the management of cancer, from initial diagnosis to the observation and management of metastases. Combined positron-emitting fluorescent contrast agents can convey new or substantial benefits that improve on these proven clinical contrast agents.