Exploring the Interplay Between Radioimmunoconjugates and Fcγ Receptors in Genetically Engineered Mouse Models of Cancer.

Fcγ receptors (FcγR) are responsible for many of the interactions between immunoglobulins (IgG) and immune cells. In biomedicine, this interplay is critical to the activity of several types of immunotherapeutics; however, relatively little is known about how FcγRs affect the in vivo performance of radiolabeled antibodies. A handful of recent preclinical studies suggest that binding by FcγR-and particularly FcγRI-can affect the pharmacokinetic profiles of Zr-labeled radioimmunoconjugates, but there are no extant studies in immunocompetent or genetically engineered mouse models of cancer.

Molecular Imaging in Gynecology: Beyond Cancer.

Gynecological pathologies account for approximately 4.5% of the overall global disease burden. Although cancers of the female reproductive system have understandably been the focus of a great deal of research, benign gynecological conditions-such as endometriosis, polycystic ovary syndrome, and uterine fibroids-have remained stubbornly understudied despite their astonishing ubiquity and grave morbidity.

Site-specific bioconjugation and nuclear imaging.

Monoclonal antibodies and antibody fragments have proven to be highly effective vectors for the delivery of radionuclides to target tissues for positron emission tomography (PET) and single-photon emission computed tomography (SPECT). However, the stochastic methods that have traditionally been used to attach radioisotopes to these biomolecules inevitably produce poorly defined and heterogeneous probes and can impair the ability of the immunoglobulins to bind their molecular targets. In response to this challenge, an array of innovative site-specific and site-selective bioconjugation strategies have been developed, and these approaches have repeatedly been shown to yield better-defined and more homogeneous radioimmunoconjugates with superior in vivo performance than their randomly modified progenitors.

Evaluating CD133 as a Radiotheranostic Target in Small-Cell Lung Cancer.

Despite decades of work, small-cell lung cancer (SCLC) remains a frustratingly recalcitrant disease. Both diagnosis and treatment are challenges: low-dose computed tomography (the approved method used for lung cancer screening) is unable to reliably detect early SCLC, and the malignancy's 5 year survival rate stands at a paltry 7%. Clearly, the development of novel diagnostic and therapeutic tools for SCLC is an urgent, unmet need.

Molecular Imaging, Radiochemistry, and Environmental Pollutants.

The worldwide proliferation of persistent environmental pollutants is accelerating at an alarming rate. Not surprisingly, many of these pollutants pose a risk to human health. In this review, we examine recent literature in which molecular imaging and radiochemistry have been harnessed to study environmental pollutants.

Site-selective radiolabeling using mushroom tyrosinase and the strain-promoted oxidation-controlled 1,2-quinone cycloaddition.

We report the characterization and evaluation of a novel Zr-labeled radioimmunoconjugate synthesized using a site-selective bioconjugation strategy based on the oxidation of tyrosinase residues exposed by the deglycosylation of the IgG and the subsequent strain-promoted oxidation-controlled 1,2-quinone cycloaddition between these amino acids and -cyclooctene-bearing cargoes. More specifically, we site-selectively modified a variant of the A33 antigen-targeting antibody huA33 with the chelator desferrioxamine (DFO), thereby producing an immunoconjugate (DFO-huA33) with equivalent antigen binding affinity to its parent immunoglobulin but attenuated affinity for the FcγRI receptor. This construct was subsequently radiolabeled with [Zr]Zr to create a radioimmunoconjugate - [Zr]Zr-DFO-huA33 - in high yield and specific activity that exhibited excellent behavior in two murine models of human colorectal carcinoma.