Measuring Extracellular pH Within Tumors Using CEST MRI

pH is one of the key microenvironmental factors in the development of tumors. Tumor cells are often viewed as high lactate and H+ producers.1 Extracellular acidosis represents a threat to cell survival by modifying the intracellular pH (pHi), wherein a 0.1 pHi variation can disrupt multiple biological functions.2 Measurements of tumor extracellular pH (pHe) may be useful for diagnosis of clinical tumors as well as for preclinical studies of cancer biology. Efficacy of a weak-base or weak-acid drug may be affected by tumor pHe, and it may also effect normal organs. Therefore, measuring pHe of tumor and normal organs may offer insight in predicting/evaluating treatment effect and facilitate treatment optimization. Chemical Exchange Saturation Transfer (CEST) MRI has been proven by multiple studies to be a practical, non-invasive method to track tumor acidosis.

Strategic Alliance with Global Specimen Solutions: Introducing SpecimINSIGHTs

The complexity of clinical trials continues to rise. New biomarkers for safety and efficacy continue to emerge, and new types of information – such as genomic profiles – have become critical to submissions for drug approval. Against this dynamic backdrop the central challenge facing trial sponsors remains the same: the need to bring together diverse data sets, draw meaningful insights from them and act quickly to maximize return on investment.

TQT Waivers: One Year Later

It has been one year since the International Conference on Harmonisation (ICH) updated its 2005 cardiac safety guidelines. The 2015 update allows for specific QT interval analysis based upon concentration effect modeling up to supratherapeutic during Phase I as a reasonable substitute for a Thorough-QT (TQT) dedicated trial.

Important Early Considerations For Assessing Drug Abuse Liability

Assessment of abuse potential of compounds in development is one of the most complex regulatory requirements and constitutes a critical exercise for sponsors and regulators. The strategy for the assessment of abuse potential cannot be customized and requires individual evaluation of the compound, its target indication and the entirety of the nonclinical and clinical safety database. In July 2016, the United States Congress passed the Comprehensive Addiction and Recovery Act (CARA) bill to address prescription opioid abuse and overdoses that have killed more than 165,000 people between 1999 and 20141.

The Need for Anatomical MRI Staging in Orthotopic Brain Models Monitored by Bioluminescence

The use of MRI to monitor the progression of brain tumors has been an accepted method both in the clinic and preclinically as well. Glioblastoma multiforme (glioblastoma; GBM) is a fast-growing glioma that develops from star-shaped glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. These tumors are usually highly malignant because the cells reproduce quickly and they are supported by a large network of blood vessels. GBM is the most common and most aggressive form of malignant primary brain tumors, affecting nearly 23,000 people in the United States annually. Most preclinical studies in glioma utilize survival as the primary endpoint, which provides limited information about disease progression or primary tumor response to treatment.

Understanding Regulatory and Market Access Considerations With Drug Abuse Potential

Each assessment for abuse liability is as unique as the molecule in question, reiterating the importance of early awareness, understanding the current regulatory landscape, and being able to plan your development and post-marketing accordingly.

Use of Luminex® Technology to Quantify Biomarkers and Provide Agent Efficacy

In recent years many researchers have focused on the analysis of circulating soluble cancer biomarkers as an indicator of the host immune response to oncogenesis.1,2,3 Multiple biomarkers can be quantified in order to fully characterize changes in homeostasis brought on by tumor growth and metastasis. The ability to multiplex tumor-type specific antigens and general immune response biomarkers in a small plasma or serum sample can provide the researcher a broad picture of test agent efficacy.

Clinical & Research Excellence Awards Shortlist Xcellerate Medical Review

We are excited to announce that Xcellerate® Medical Review has been named a finalist in the Clinical & Research Excellence (CARE) Awards. As a finalist in the Best Sponsor-Focused Technological Development category, Xcellerate Medical Review is being recognized for its modern approach to improving the clinical trial process. The CARE Awards recognize excellence across the global clinical research enterprise.

Phase I cGMP Drug Manufacture at the CRU: 3 BIG Benefits

The regulatory environment continues to move toward requiring drug manufacturing at current good manufacturing practice (cGMP)-compliant pharmacies. This trend and other factors make it increasingly attractive to use cGMP compounding on-site at your CRU for early development. Let’s look at Three Big Benefits for Phase I drug manufacturing:

Preclinical Success to Clinical Failure: Do We Have a Model Problem or an Endpoint Problem?

As the AACR (American Association for Cancer Research) Annual Meeting is fast approaching, many industry and academic scientists are busy preparing talks and posters for what they hope will be the next new wave in cancer therapy or the next “new and improved” preclinical model. However, while these may be long shots, it’s the scientific drive for improvement that keeps us moving forward. As, patients and clinicians, we are desperately looking for new therapies, even if the odds are against us. The desire to fulfill that unmet medical need is exactly how the one new drug is discovered. New oncology drugs only have a 5% success rate once making it from Phase I clinical trials to FDA approval. This is the lowest success rate among the 21 major disease indications.1