In Vivo PET Detection of Lung Micrometastasis in Mice by Targeting Endothelial VCAM-1 Using a Dual-Contrast PET/MRI Probe.

Current clinical diagnostic imaging methods for lung metastases are sensitive only to large tumours (1-2 mm cross-sectional diameter), and early detection can dramatically improve treatment. We have previously demonstrated that an antibody-targeted MRI contrast agent based on microparticles of iron oxide (MPIO; 1 µm diameter) enables the imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Using a mouse model of lung metastasis, upregulation of endothelial VCAM-1 expression was demonstrated in micrometastasis-associated vessels but not in normal lung tissue, and binding of VCAM-MPIO to these vessels was evident histologically. Owing to the lack of proton MRI signals in the lungs, we modified the VCAM-MPIO to include zirconium-89 (89Zr, t1/2 = 78.4 h) in order to allow the in vivo detection of lung metastases by positron emission tomography (PET). Using this new agent (89Zr-DFO-VCAM-MPIO), it was possible to detect the presence of micrometastases within the lung in vivo from ca. 140 µm in diameter. Histological analysis combined with autoradiography confirmed the specific binding of the agent to the VCAM-1 expressing vasculature at the sites of pulmonary micrometastases. By retaining the original VCAM-MPIO as the basis for this new molecular contrast agent, we have created a dual-modality (PET/MRI) agent for the concurrent detection of lung and brain micrometastases.

Enhancing [177Lu]Lu-DOTA-TATE therapeutic efficacy in vitro by combining it with metronomic chemotherapeutics.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) uses [177Lu]Lu-[DOTA0-Tyr3]octreotate ([177Lu]Lu-DOTA-TATE) to treat patients with neuroendocrine tumours (NETs) overexpressing the somatostatin receptor 2A (SSTR2A). It has shown significant short-term improvements in survival and symptom alleviation, but there remains room for improvement. Here, we investigated whether combining [177Lu]Lu-DOTA-TATE with chemotherapeutics enhanced the in vitro therapeutic efficacy of [177Lu]Lu-DOTA-TATE. RESULTS: Transfected human osteosarcoma (U2OS + SSTR2A, high SSTR2A expression) and pancreatic NET (BON1 + STTR2A, medium SSTR2A expression) cells were subjected to hydroxyurea, gemcitabine or triapine for 24 h at 37oC and 5% CO2. Cells were then recovered for 4 h prior to a 24-hour incubation with 0.7-1.03 MBq [177Lu]Lu-DOTA-TATE (25 nM) for uptake and metabolic viability studies. Incubation of U2OS + SSTR2A cells with hydroxyurea, gemcitabine, and triapine enhanced uptake of [177Lu]Lu-DOTA-TATE from 0.2 ± 0.1 in untreated cells to 0.4 ± 0.1, 1.1 ± 0.2, and 0.9 ± 0.2 Bq/cell in U2OS + SSTR2A cells, respectively. Cell viability post treatment with [177Lu]Lu-DOTA-TATE in cells pre-treated with chemotherapeutics was decreased compared to cells treated with [177Lu]Lu-DOTA-TATE monotherapy. For example, the viability of U2OS + SSTR2A cells incubated with [177Lu]Lu-DOTA-TATE decreased from 59.5 ± 22.3% to 18.8 ± 5.2% when pre-treated with hydroxyurea. Control conditions showed no reduced metabolic viability. Cells were also harvested to assess cell cycle progression, SSTR2A expression, and cell size by flow cytometry. Chemotherapeutics increased SSTR2A expression and cell size in U2OS + SSTR2A and BON1 + STTR2A cells. The S-phase sub-population of asynchronous U2OS + SSTR2A cell cultures was increased from 45.5 ± 3.3% to 84.8 ± 2.5%, 85.9 ± 1.9%, and 86.6 ± 2.2% when treated with hydroxyurea, gemcitabine, and triapine, respectively. CONCLUSIONS: Hydroxyurea, gemcitabine and triapine all increased cell size, SSTR2A expression, and [177Lu]Lu-DOTA-TATE uptake, whilst reducing cell metabolic viability in U2OS + SSTR2A cells when compared to [177Lu]Lu-DOTA-TATE monotherapy. Further investigations could transform patient care and positively increase outcomes for patients treated with [177Lu]Lu-DOTA-TATE.

Intraoperative application of three-dimensional printed guides in total hip arthroplasty: A systematic review.

BACKGROUND: Acetabular component positioning in total hip arthroplasty (THA) is of key importance to ensure satisfactory post-operative outcomes and to minimize the risk of complications. The majority of acetabular components are aligned freehand, without the use of navigation methods. Patient specific instruments (PSI) and three-dimensional (3D) printing of THA placement guides are increasingly used in primary THA to ensure optimal positioning. AIM: To summarize the literature on 3D printing in THA and how they improve acetabular component alignment. METHODS: PubMed was used to identify and access scientific studies reporting on different 3D printing methods used in THA. Eight studies with 236 hips in 228 patients were included. The studies could be divided into two main categories; 3D printed models and 3D printed guides. RESULTS: 3D printing in THA helped improve preoperative cup size planning and post-operative Harris hip scores between intervention and control groups (P = 0.019, P = 0.009). Otherwise, outcome measures were heterogeneous and thus difficult to compare. The overarching consensus between the studies is that the use of 3D guidance tools can assist in improving THA cup positioning and reduce the need for revision THA and the associated costs. CONCLUSION: The implementation of 3D printing and PSI for primary THA can significantly improve the positioning accuracy of the acetabular cup component and reduce the number of complications caused by malpositioning.

A novel method to perform morphological measurements on three-dimensional (3D) models of the calcaneus based on computed tomography (CT)-imaging.

Background: While current preoperative and postoperative assessment of the fractured and surgically reconstructed calcaneus relies on computed tomography (CT)-imaging, there are no established methods to quantify calcaneus morphology on CT-images. This study aims to develop a semi-automated method for morphological measurements of the calcaneus on three-dimensional (3D) models derived from CT-imaging. Methods: Using CT data, 3D models were created from healthy, fractured, and surgically reconstructed calcanei. Böhler's angle (BA) and Critical angle of Gissane (CAG) were measured on conventional lateral radiographs and corresponding 3D CT reconstructions using a novel point-based method with semi-automatic landmark placement by three observers. Intraobserver and interobserver reliability scores were calculated using intra-class correlation coefficient (ICC). In addition, consensus among observers was calculated for a maximal allowable discrepancy of 5 and 10 degrees for both methods. Results: Imaging data from 119 feet were obtained (40 healthy, 39 fractured, 40 reconstructed). Semi-automated measurements on 3D models of BA and CAG showed excellent reliability (ICC: 0.87-1.00). The manual measurements on conventional radiographs had a poor-to-excellent reliability (ICC: 0.22-0.96). In addition, the percentage of consensus among observers was much higher for the 3D method when compared to conventional two-dimensional (2D) measurements. Conclusions: The proposed method enables reliable and reproducible quantification of calcaneus morphology in 3D models of healthy, fractured and reconstructed calcanei.