Targeted chain-exchange-mediated reconstitution of a split type-I cytokine for conditional immunotherapy.

Antibody-cytokine fusions targeted against tumor-associated antigens (TAAs) are promising cancer immunotherapy agents, with many such molecules currently undergoing clinical trials. However, due to the limited number of tumor-specific targets, on-target off-tumor effects can lead to systemic toxicity. Additionally, targeted cytokines can be scavenged by cytokine receptors on peripheral cells, decreasing tumor penetration.

Development of C1q Affinity Chromatography for the Study of C1q-IgG Interactions.

The classical complement system represents a central effector mechanism of Abs initiated by the binding of C1q to target bound IgG. Human C1q contains six heterotrimeric globular head groups that mediate IgG interaction, resulting in an avidity-driven binding event involving multiple IgG molecules binding a single C1q. Accordingly, surface bound IgG molecules are thought to assemble into noncovalent hexameric rings for optimal binding to the six-headed C1q.

CD3 Target Affinity Chromatography Mass Spectrometry as a New Tool for Function-Structure Characterization of T-Cell Engaging Bispecific Antibody Proteoforms and Product-Related Variants.

T-cell engaging bispecific antibodies (TCBs) targeting CD3 and tumor-specific antigens are very promising therapeutic modalities. Since CD3 binding is crucial for the potency of TCBs, understanding the functional impact of CD3 antigen-binding fragment modifications is of utmost importance for defining critical quality attributes (CQA). The current CQA assessment strategy requires the integration of structure-based physicochemical separation and functional cell-based potency assays.

Back-to-Germline (B2G) Procedure for Antibody Devolution.

Bispecific antibodies (bsAbs) with avidity-enhanced specificity can be used to address target cells with increased specificity, ideally binding efficiently to cells that express two cognate antigens, yet not to cells that express only one of those. Building blocks required to generate such bsAbs are binders that recognize the two antigens with high specificity yet with various (including very low monovalent) affinities. The herein described 'back-to-germline' (B2G) procedure defines such derivatives.

Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing.

A novel bispecific antibody format was applied to generate T cell-engaging antibodies. The TriFab format is a trivalent IgG-shaped entity composed of two Fab arms that bind to antigens on the surface of tumor cells, which are linked via flexible peptides to a CD3 binding moiety that replaces the CH2 domains of conventional IgGs. The distinctive feature of these T cell recruiting bispecifics is that their CD3 variable regions are incorporated between domains, rather than N- or C-terminally fused to an Fc or antibody fragments.

The Binding of Human IgG to Minipig FcγRs - Implications for Preclinical Assessment of Therapeutic Antibodies.

Purpose: The Göttingen minipig is a relevant non-rodent species for regulatory toxicological studies. Yet, its use with therapeutic antibodies has been limited by the unknown binding properties of human immunoglobulins (huIgG) to porcine Fc gamma receptors (poFcγR) influencing safety and efficacy readouts. Therefore, knowing IgG-FcγR interactions in the animal model is a prerequisite for the use of minipigs in preclinical safety and efficacy studies with therapeutic antibodies.

Quantitative Apparent Diffusion Coefficient Derived From Diffusion-Weighted Imaging Has the Potential to Avoid Unnecessary MRI-Guided Biopsies of mpMRI-Detected PI-RADS 4 and 5 Lesions.

Objective: The aim of this study was to evaluate the potential of diffusion-weighted imaging-derived apparent diffusion coefficient (ADC) measurements to obviate unnecessary biopsies in multiparametric MRI-detected PI-RADS 4 and 5 lesions.

Materials And Methods: This retrospective, institutional review board-approved study investigated 101 PI-RADS 4 and 5 prostate lesions (52 malignant, 49 benign) verified by in-bore MRI-guided biopsy in 101 men (mean age, 62.8 years).

3 Tesla breast MR imaging as a problem-solving tool: Diagnostic performance and incidental lesions.

Purpose: To investigate the diagnostic performance and incidental lesion yield of 3T breast MRI if used as a problem-solving tool.

Methods: This retrospective, IRB-approved, cross-sectional, single-center study comprised 302 consecutive women (mean: 50±12 years; range: 20-79 years) who were undergoing 3T breast MRI between 03/2013-12/2014 for further workup of conventional and clinical breast findings. Images were read by experienced, board-certified radiologists.

Potential of Noncontrast Magnetic Resonance Imaging With Diffusion-Weighted Imaging in Characterization of Breast Lesions: Intraindividual Comparison With Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

Objectives: The aim of this study was to assess the potential of noncontrast magnetic resonance imaging (NC-MRI) with diffusion-weighted imaging (DWI) in characterization of breast lesions in comparison to dynamic contrast-enhanced MRI (DCE-MRI) at 3 T.

Materials And Methods: Consecutive patients with conventional imaging (mammography, ultrasound) BI-RADS 4/5 findings were included in this institutional review board-approved single-center study. All underwent 3 T breast MRI including readout-segmented DWI, DCE, and T2-weighted sequences.

Breast lesions classified as probably benign (BI-RADS 3) on magnetic resonance imaging: a systematic review and meta-analysis.

Purpose: To investigate prevalence, malignancy rates, imaging features, and follow-up intervals for probably benign (BI-RADS 3) lesions on breast magnetic resonance imaging (MRI).

Methods: A systematic database-review of articles published through 22/06/2016 was performed. Eligible studies reported BI-RADS 3 lesions on breast MRI.

3D T2-weighted imaging to shorten multiparametric prostate MRI protocols.

Objectives: To determine whether 3D acquisitions provide equivalent image quality, lesion delineation quality and PI-RADS v2 performance compared to 2D acquisitions in T2-weighted imaging of the prostate at 3 T.

Methods: This IRB-approved, prospective study included 150 consecutive patients (mean age 63.7 years, 35-84 years; mean PSA 7.

A simple classification system (the Tree flowchart) for breast MRI can reduce the number of unnecessary biopsies in MRI-only lesions.

Objectives: To assess whether using the Tree flowchart obviates unnecessary magnetic resonance imaging (MRI)-guided biopsies in breast lesions only visible on MRI.

Methods: This retrospective IRB-approved study evaluated consecutive suspicious (BI-RADS 4) breast lesions only visible on MRI that were referred to our institution for MRI-guided biopsy. All lesions were evaluated according to the Tree flowchart for breast MRI by experienced readers.

Human Biodistribution and Radiation Dosimetry of F-Clofarabine, a PET Probe Targeting the Deoxyribonucleoside Salvage Pathway.

F-clofarabine, a nucleotide purine analog, is a substrate for deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. F-clofarabine might be used to measure dCK expression and thus serve as a predictive biomarker for tumor responses to dCK-dependent prodrugs or small-molecule dCK inhibitors, respectively. As a prerequisite for clinical translation, we determined the human whole-body and organ dosimetry of F-clofarabine.

Malignancy rates and diagnostic performance of the Bosniak classification for the diagnosis of cystic renal lesions in computed tomography - a systematic review and meta-analysis.

Objective: To systematically review the literature on the Bosniak classification system in CT to determine its diagnostic performance to diagnose malignant cystic lesions and the prevalence of malignancy in Bosniak categories.

Methods: A predefined database search was performed from 1 January 1986 to 18 January 2016. Two independent reviewers extracted data on malignancy rates in Bosniak categories and several covariates using predefined criteria.

Evaluation of Prostate Cancer with 11C-Acetate PET/CT.

In this article, we will first describe the metabolic fate of C-acetate; then discuss its biodistribution in health and disease; and subsequently focus on its key clinical applications, the detection and localization of prostate cancer tissue in patients with primary or recurrent disease. Finally, we will discuss the potential role of C-acetate in the context of other prostate cancer imaging probes and non-radionuclide-based imaging approaches.

Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions.

Recombinant human IgG antibodies (hIgGs) completely devoid of binding to Fcγ receptors (FcγRs) and complement protein C1q, and thus with abolished immune effector functions, are of use for various therapeutic applications in order to reduce FcγR activation and Fc-mediated toxicity. Fc engineering approaches described to date only partially achieve this goal or employ a large number of mutations, which may increase the risk of anti-drug antibody generation. We describe here two new, engineered hIgG Fc domains, hIgG1-P329G LALA and hIgG4-P329G SPLE, with completely abolished FcγR and C1q interactions, containing a limited number of mutations and with unaffected FcRn interactions and Fc stability.

Diffusion-weighted imaging of breast lesions: Region-of-interest placement and different ADC parameters influence apparent diffusion coefficient values.

Objectives: To investigate the influence of region-of-interest (ROI) placement and different apparent diffusion coefficient (ADC) parameters on ADC values, diagnostic performance, reproducibility and measurement time in breast tumours.

Methods: In this IRB-approved, retrospective study, 149 histopathologically proven breast tumours (109 malignant, 40 benign) in 147 women (mean age 53.2) were investigated.

Diffusion-weighted MRI of breast lesions: a prospective clinical investigation of the quantitative imaging biomarker characteristics of reproducibility, repeatability, and diagnostic accuracy.

Diffusion-weighted MRI (DWI) provides insights into tissue microstructure by visualization and quantification of water diffusivity. Quantitative evaluation of the apparent diffusion coefficient (ADC) obtained from DWI has been proven helpful for differentiating between malignant and benign breast lesions, for cancer subtyping in breast cancer patients, and for prediction of response to neoadjuvant chemotherapy. However, to further establish DWI of breast lesions it is important to evaluate the quantitative imaging biomarker (QIB) characteristics of reproducibility, repeatability, and diagnostic accuracy.

68Ga-DOTATATE PET/CT Interobserver Agreement for Neuroendocrine Tumor Assessment: Results of a Prospective Study on 50 Patients.

Unlabelled: We evaluated observer agreement for Ga-DOTATATE PET/CT interpretations in patients with neuroendocrine tumor (NET).

Methods: Ga-DOTATATE PET/CT was performed on 50 patients with known or suspected NET of the small bowel (n = 19), pancreas (n = 14), lung (n = 4), or other location (n = 13). The images were reviewed by 7 observers, who used a standardized interpretation approach.

Automatic quantification of multi-modal rigid registration accuracy using feature detectors.

In radiotherapy, the use of multi-modal images can improve tumor and target volume delineation. Images acquired at different times by different modalities need to be aligned into a single coordinate system by 3D/3D registration. State of the art methods for validation of registration are visual inspection by experts and fiducial-based evaluation.

Synthesis and preclinical evaluation of an AlF radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand.

Purpose: The aim of this study was to synthesize and preclinically evaluate an F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined.

Methods: Several conditions for the labeling of F-PSMA-11 via F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time.

Clinical application of Acoustic Radiation Force Impulse Imaging with Virtual Touch IQ in breast ultrasound: diagnostic performance and reproducibility of a new technique.

Background Virtual Touch IQ (VTIQ) is a novel technique of quantitative sonoelastography that applies acoustic radiation force impulse (ARFI). Purpose To evaluate breast ARFI imaging with VTIQ in the clinical setting, with regard to reproducibility and diagnostic performance, and to specify cutoff limits for the differentiation of benign and malignant lesions. Material and Methods This retrospective study included 83 patients with 85 breast lesions (51 benign, 34 malignant) who received ARFI imaging with VTIQ.

MR-guided vacuum-assisted breast biopsy of MRI-only lesions: a single center experience.

Purpose: The purpose of this study was to compare three different biopsy devices on false-negative and underestimation rates in MR-guided, vacuum-assisted breast biopsy (VABB) of MRI-only lesions.

Methods: This retrospective, single-center study was IRB-approved. Informed consent was waived.

18F-FDG PET/CT and PET/MRI Perform Equally Well in Cancer: Evidence from Studies on More Than 2,300 Patients.

(18)F-FDG PET/CT has become the reference standard in oncologic imaging against which the performance of other imaging modalities is measured. The promise of PET/MRI includes multiparametric imaging to further improve diagnosis and phenotyping of cancer. Rather than focusing on these capabilities, many investigators have examined whether (18)F-FDG PET combined with mostly anatomic MRI improves cancer staging and restaging.