PYTA: a universal chelator for advancing the theranostic palette of nuclear medicine.

To clinically advance the growing arsenal of radiometals available to image and treat cancer, chelators with versatile binding properties are needed. Herein, we evaluated the ability of the py[18]dieneN macrocycle PYTA to interchangeably bind and stabilize Ac, [Lu]Lu, [In]In and [Sc]Sc, a chemically diverse set of radionuclides that can be used complementarily for targeted alpha therapy, beta therapy, single-photon emission computed tomography (SPECT) imaging, and positron emission tomography (PET) imaging, respectively. Through NMR spectroscopy and X-ray diffraction, we show that PYTA possesses an unusual degree of flexibility for a macrocyclic chelator, undergoing dramatic conformational changes that enable it to optimally satisfy the disparate coordination properties of each metal ion.

Engineering a modular Ti/Sc generator: eluate evaluation in preclinical models and estimation of human radiation dosimetry.

Background: Sc/Sc is an attractive theranostic pair for targeted in vivo positron emission tomographic (PET) imaging and beta-particle treatment of cancer. The Ti/Sc generator allows daily onsite production of this diagnostic isotope, which may provide an attractive alternative for PET facilities that lack in-house irradiation capabilities. Early animal and patient studies have demonstrated the utility of Sc.

Improved Radium-223 Therapy with Combination Epithelial Sodium Channel Blockade.

Radium-223 dichloride ([Ra]RaCl2) is the first approved alpha particle-emitting therapy and is indicated for treatment of bone metastatic castrate resistant prostate cancer. Approximately half of the dose is absorbed into the gastrointestinal (GI) tract within minutes of administration, limiting disease-site uptake and contributing to toxicity. Here, we investigate the role of enteric ion channels and their modulation for improved therapeutic efficacy and reduced side effects.