Synthesis and evaluation of novel PD-L1-targeted small molecules for 18F-labeling and PET imaging
Conclusions: To develop small molecule-based PD-L1 PET imaging probes, we designed and synthesized a library of fluorinated PD-L1 ligands based on the biphenyl pharmacophore. In vitro binding assay showed that several of the compounds possess nano-molar affinities to human PD-L1, and are potential PD-L1 PET imaging probe candidates. The radiolabeling and in vitro and in vivo pharmacology and pharmacokinetics studies of these PET tracers are under the way. Figure 1. The structure of the lead compound and the regions for SAR
Conclusions The recent, first randomized clinical trial demonstrated overall and progression free survival benefits after SBRT to oligometastatic disease which supports prior retrospective case series (6). The spine is a common site of metastatic bone disease, and as high quality data continue to mature, along with completion of additional randomized clinical trials, it is expected that utility of SBRT to the spine will increase in the future. Spine SBRT is unique due to the requirement of sharp dose falloff to prevent serious neurologic morbidity. With recent advances in radiotherapy planning, robotic patient positionin...
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
CONCLUSIONSThis expanded and updated analysis confirms that single-fraction preoperative SRS confers excellent cavity local control with very low risk of RN or LMD. Preoperative SRS has several potential advantages compared to postoperative SRS, including reduced risk of RN due to smaller irradiated volume without need for cavity margin expansion and reduced risk of LMD due to sterilization of tumor cells prior to spillage at the time of surgery. Subtotal resection, though infrequent, is associated with significantly worse cavity LR and OS. Based on these results, a randomized trial of preoperative versus postoperative SRS...
Brain metastases (BM) are the most common intracranial neoplastic disease in adults, with an incidence of 9 –17% among all brain tumors (Nayak et al., 2012). They are usually caused by lung cancer (either non-small cell (NSCLC) and small cell (SCLC) histologies), breast cancer, melanoma and renal cell carcinoma, with a raising incidence related to the improvements in diagnostic and treatment approaches (Berghoff et al., 2014). However, prognosis remains poor, with a median overall survival (OS) ranging from 3 to 27 months (Brastianos et al., 2013), rendering BM still an unmet medical need.
Brain metastases (BM) are the most common intracranial neoplastic disease in adults, with an incidence of 9-17% among all brain tumors (Nayak et al., 2012). They are usually caused by lung cancer (either non-small cell (NSCLC) and small cell (SCLC) histologies), breast cancer, melanoma and renal cell carcinoma, with a raising incidence related to the improvements in diagnostic and treatment approaches (Berghoff et al., 2014). However, prognosis remains poor, with a median overall survival (OS) ranging from 3 to 27 months (Brastianos et al., 2013), rendering BM still an unmet medical need.
Radiation is hypothesized to augment the immunogenicity of tumor cells. We retrospectively evaluated survival outcomes, incidence of new brain metastases, and treatment-related adverse events in patients who received stereotactic radiosurgery for brain metastases with concurrent immune checkpoint inhibition, with non-concurrent immune checkpoint inhibition, and with stereotactic radiosurgery alone. Delivering SRS with concurrent ICI may be associated with decreased incidence of new BM and favorable survival outcomes without increased rates of adverse events.
Patients with metastatic melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) are increasingly treated with immune checkpoint blockade targeting the programed death (PD)-1 receptor, often with palliative radiation therapy. Outcome data are limited in this population.
CONCLUSIONS: Incorporation of palliative radiation does not preclude favorable outcomes in patients treated with PD-1 inhibitors; patients irradiated after the start of PD-1 inhibition can remain on therapy and demonstrate prolonged survival. Of note, patients irradiated for brain metastases demonstrate favorable outcomes compared with historical controls. PMID: 28662869 [PubMed - as supplied by publisher]
Abstract OBJECTIVE The impact of the stereotactic radiosurgery (SRS) prescription dose (PD) on local progression and radiation necrosis for small (≤ 2 cm) brain metastases was evaluated. METHODS An institutional review board-approved retrospective review was performed on 896 patients with brain metastases ≤ 2 cm (3034 tumors) who were treated with 1229 SRS procedures between 2000 and 2012. Local progression and/or radiation necrosis were the primary end points. Each tumor was followed from the date of radiosurgery until one of the end points was reached or the last MRI follow-up. Various criteria were used t...
Nivolumab has been approved by the Food and Drug Administration to treat advanced non-small cell lung cancer, renal cell carcinoma, and melanoma; however, the impact of nivolumab on brain metastases is unclear.01/28/2016
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