Towards Imaging Pt Chemoresistance Using Gd(III)-Pt(II) Theranostic MR Contrast Agents.

Cisplatin and related Pt(II) chemotherapeutics are indispensable tools for the treatment of various solid tumors. Despite their widespread clinical use in approximately 50 % of chemotherapy regimens, they are hindered by issues with off-target toxicity and chemoresistance, both innate and acquired. To date, there is no effective way to predict the outcome of Pt(II) chemotherapy because the genes associated with resistance are not completely known or understood.

Gd(iii)-Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy.

Pt(iv) prodrugs have emerged as versatile therapeutics for addressing issues regarding off-target toxicity and the chemoresistance of classic Pt(ii) drugs such as cisplatin and carboplatin. There is significant potential for Pt(iv) complexes to be used as theranostic agents, yet there are currently no reported examples of Gd(iii)-Pt(iv) agents for simultaneous MR imaging and chemotherapy. Here we report the synthesis, characterization, and efficacy of two Gd(iii)-Pt(iv) agents, and .

A Multimodal Ca(II) Responsive Near IR-MR Contrast Agent Exhibiting High Cellular Uptake.

Ca(II) ions are critical for the proper function of neurons by contributing to synaptic signaling and regulating neuronal plasticity. Dysregulation of Ca(II) is associated with a number of pathologies that cause neurodegeneration; therefore the ability to monitor Ca(II) intracellularly is an important target for molecular imaging. Contrast-enhanced MR imaging is a promising modality for imaging changes in Ca(II) concentrations.

Synthesis, Characterization, and Nanomaterials Generated from 6,6'-(((2-Hydroxyethyl)azanediyl)bis(methylene))bis(2,4-di- tert-butylphenol) Modified Group 4 Metal Alkoxides.

The impact on the morphology nanoceramic materials generated from group 4 metal alkoxides ([M(OR)]) and the same precursors modified by 6,6'-(((2-hydroxyethyl)azanediyl)bis(methylene))bis(2,4-di- tert-butylphenol) (referred to as H-AM-DBP (1)) was explored. The products isolated from the 1:1 stoichiometric reaction of a series of [M(OR)] where M = Ti, Zr, or Hf; OR = OCH(CH)(OPr ); OC(CH)(OBu ); OCHC(CH)(ONep) with H-AM-DBP proved, by single crystal X-ray diffraction, to be [(ONep)Ti( k( O,O',O'',N)-AM-DBP)] (2), [(OR)M(μ( O)- k( O',O'',N)-AM-DBP)] [M = Zr: OR = OPr , 3·tol; OBu , 4·tol; ONep, 5·tol; M = Hf: OR = OBu , 6·tol; ONep, 7·tol]. The product from each system led to a tetradentate AM-DBP ligand and retention of a parent alkoxide ligand.

Multifunctional Desferrichrome Analogues as Versatile Zr(IV) Chelators for ImmunoPET Probe Development.

New bifunctional hexa- and octadentate analogues of the hydroxamate-containing siderophore desferrichrome (DFC) have been synthesized and evaluated as Zr-chelating agents for immunoPET applications. The in vitro and in vivo inertness of these new ligands, Orn3-hx (hexadentate) and Orn-4hx derivatives (octadentate), was compared to the gold standard hexadentate, hydroxamate-containing chelator for Zr desferrioxamine (DFO). Density functional theory was employed to model the geometries of the resulting Zr(IV) complexes and to predict their relative stabilities as follows: Zr(Orn4-hx) > Zr(DFC) > Zr(Orn3-hx).