¹⁸F-fluoride PET as a noninvasive imaging biomarker for determining treatment efficacy of bone active agents at the hip: a prospective, randomized, controlled clinical study.

The functional imaging technique of ¹⁸F-fluoride positron emission tomography (¹⁸F-PET) allows the noninvasive quantitative assessment of regional bone formation at any skeletal site, including the spine and hip. The aim of this study was to determine if ¹⁸F-PET can be used as an early biomarker of treatment efficacy at the hip. Twenty-seven treatment-naive postmenopausal women with osteopenia were randomized to receive teriparatide and calcium and vitamin D (TPT group, n = 13) or calcium and vitamin D only (control group, n = 14).

Downregulation of 18F-FDG uptake in PET as an early pharmacodynamic effect in treatment of non-small cell lung cancer with the mTOR inhibitor everolimus.

Unlabelled: Everolimus downregulates glucose metabolism-associated genes in preclinical models. Inhibition of glucose metabolism measured by (18)F-FDG PET was postulated to serve as a pharmacodynamic marker in everolimus-treated non-small cell lung cancer (NSCLC) patients.

Methods: In 8 NSCLC patients treated with everolimus, the percentage change in (18)F-FDG PET uptake (days 8 and 28 relative to baseline) was determined using a variety of summed standardized uptake value (SUV) measures.

Discovery of potent, selective, and orally active carboxylic acid based inhibitors of matrix metalloproteinase-13.

The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would therefore be a novel disease modifying therapy for the treatment of arthritis. Our efforts have resulted in the discovery of a series of carboxylic acid inhibitors of MMP-13 that do not significantly inhibit the related MMP-1 (collagenase-1) or tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE).

Colorectal liver metastases: contrast agent diffusion coefficient for quantification of contrast enhancement heterogeneity at MR imaging.

Purpose: To describe and determine the reproducibility of a simplified model to quantitatively measure heterogeneous intralesion contrast agent diffusion in colorectal liver metastases.

Materials And Methods: This HIPAA-compliant retrospective study received institutional review board approval, and written informed consent was obtained from 14 patients (mean age, 61 years +/- 9 [standard deviation]; range, 41-78 years), including 10 men (mean age, 65 years +/- 8; range, 47-78 years) and four women (mean age, 54 years +/- 9; range, 41-59 years), with colorectal liver metastases. Magnetic resonance (MR) imaging was performed twice (first baseline MR image [B(1)] and second baseline MR image [B(2)]) in a single target lesion prior to therapy.

In vivo MRI of cartilage pathogenesis in surgical models of osteoarthritis.

Objective: To examine in vivo time-course changes in macromolecular composition of articular cartilage in two surgical models of osteoarthritis (goat: meniscal transection and cartilage incision; rabbit: medial meniscectomy).

Design: Collagen integrity and proteoglycan (PG) content were evaluated in both models by magnetization transfer (MT) and contrast-enhanced MRI, respectively. The MT rate k(m) for the exchange process between the bulk water and water bound to collagen was determined as a marker of the collagen network.

Pain related behaviour in two models of osteoarthritis in the rat knee.

Osteoarthritis (OA) is a major healthcare burden, with increasing incidence. Pain is the predominant clinical feature, yet therapy is ineffective for many patients. While there are considerable insights into the mechanisms underlying tissue remodelling, there is poor understanding of the link between disease pathology and pain.

In vivo assessment of macromolecular content in articular cartilage of the goat knee.

Loss of proteoglycans (PGs) from the extracellular matrix of cartilage is an early event of osteoarthritis. The capability of Gd(DTPA)(2-)-enhanced MRI to quantitatively assess PG content was explored in a goat model of cartilage degeneration. Partial to total PG depletion was induced by an intraarticular injection of papain 1 day prior to the MRI session.

Qualitative and quantitative in vivo assessment of articular cartilage using magnetic resonance imaging.

The molecular organization and biochemical composition that give cartilage the viscoelasticity necessary for load distribution also convey unique magnetic resonance (MR) properties. In that context, MR imaging has the potential to detect cartilage degeneration and regeneration. Magnetization transfer (MT) imaging probes the exchange of magnetization between the bulk water pool and the water pool bound to macromolecules such as collagen and hence MT may be applied for evaluation of collagen integrity.

Fluorescently labeled mesenchymal stem cells (MSCs) maintain multilineage potential and can be detected following implantation into articular cartilage defects.

Several studies have reported enhanced repair of damaged cartilage following implantation of mesenchymal stem cells (MSCs) into full-thickness cartilage defects suggesting that the cells in the repair tissue were derived from the implant. However, it cannot be excluded that the enhanced tissue repair is derived from host cells recruited to the defect in response to the implant, rather than the re-population of the tissue by the implanted MSCs. Our objective was to study the short-term fate of fluorescently labeled MSCs after implantation into full-thickness cartilage defects in vivo.