Development of a CCR2 targeted 18F-labeled radiotracer for atherosclerosis imaging with PET.

Atherosclerosis is a chronic inflammatory disease and the leading cause of morbidity and mortality worldwide. CC motif chemokine ligand 2 and its corresponding cognate receptor 2 (CCL2/CCR2) signaling has been implicated in regulating monocyte recruitment and macrophage polarization during inflammatory responses that plays a pivotal role in atherosclerosis initiation and progression. In this study, we report the design and synthesis of a novel 18F radiolabeled small molecule radiotracer for CCR2-targeted positron emission tomography (PET) imaging in atherosclerosis. The binding affinity of this radiotracer to CCR2 was evaluated via in vitro binding assay using CCR2+ membrane and cells. Ex vivo biodistribution was carried out in wild type mice to assess radiotracer pharmacokinetics. CCR2 targeted PET imaging of plaques was performed in two murine atherosclerotic models. The sensitive detection of atherosclerotic lesions highlighted the potential of this radiotracer for CCR2 targeted PET and warranted further optimization.

Prevalence of Women in Medicine Programs at University-Based Internal Medicine Residency Programs.

OBJECTIVE: Women physicians face various forms of inequities during their training process that inhibit them from reaching their full potential. As a response, several academic institutions have established women in medicine (WIM) programs as a support system. Our objective was to investigate the prevalence of WIM programs at university-based Internal Medicine residency programs as of December 2021. METHODS: Using the Fellowship and Residency Electronic Interactive Database, we identified 145 university-based Internal Medicine residency programs. Four independent reviewers reviewed the programs' Web sites, looking for evidence of a WIM program using a standardized checklist of search terms to evaluate and categorize their programs. Categories included whether the program was specific to graduate medical trainees, departments of medicine, or institution-wide. The proportions of programs that had a WIM program, a trainee-specific WIM program, and a Department of Medicine-specific WIM program were then analyzed. RESULTS: Of the 145 programs searched, 58 (40%) had a WIM program. Only 16 (11%) were specific to trainees (11 for only medicine trainees and 5 included trainees graduate medical education-wide). The remaining 42 programs targeted faculty and trainees (5 included only the Department of Medicine and 37 included departments university-wide). CONCLUSIONS: Few university-affiliated Internal Medicine residency programs have a WIM program specific to trainees. Given the gender inequity and evidence that supports early development of leadership skills and support networks, our findings highlight a possible gap in the residency training program infrastructure.

Chemokine Receptor 2 Targeted PET/CT Imaging Distant Metastases in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and treatment-refractory malignancies. The lack of an effective screening tool results in the majority of patients being diagnosed at late stages, which underscores the urgent need to develop more sensitive and specific imaging modalities, particularly in detecting occult metastases, to aid clinical decision-making. The tumor microenvironment of PDAC is heavily infiltrated with myeloid-derived suppressor cells (MDSCs) that express C-C chemokine receptor type 2 (CCR2). These CCR2-expressing MDSCs accumulate at a very early stage of metastasis and greatly outnumber PDAC cells, making CCR2 a promising target for detecting early, small metastatic lesions that have scant PDAC cells. Herein, we evaluated a CCR2 targeting PET tracer (68Ga-DOTA-ECL1i) for PET imaging on PDAC metastasis in two mouse models. Positron emission tomography/computed tomography (PET/CT) imaging of 68Ga-DOTA-ECL1i was performed in a hemisplenic injection metastasis model (KI) and a genetically engineered orthotopic PDAC model (KPC), which were compared with 18F-FDG PET concurrently. Autoradiography, hematoxylin and eosin (H&E), and CCR2 immunohistochemical staining were performed to characterize the metastatic lesions. PET/CT images visualized the PDAC metastases in the liver/lung of KI mice and in the liver of KPC mice. Quantitative uptake analysis revealed increased metastasis uptake during disease progression in both models. In comparison, 18F-FDG PET failed to detect any metastases during the time course studies. H&E staining showed metastases in the liver and lung of KI mice, within which immunostaining clearly demonstrated the overexpression of CCR2 as well as CCR2+ cell infiltration into the normal liver. H&E staining, CCR2 staining, and autoradiography also confirmed the expression of CCR2 and the uptake of 68Ga-DOTA-ECL1i in the metastatic foci in KPC mice. Using our novel CCR2 targeted radiotracer 68Ga-DOTA-ECL1i and PET/CT, we demonstrated the sensitive and specific detection of CCR2 in the early PDAC metastases in two mouse models, indicating its potential in future clinical translation.

Pancreatic tail cancer in the setting of pancreatitis with a review of the literature: A case report.

Environmental risk factors for pancreatic cancer include acute and chronic pancreatitis, obesity, and tobacco use. Differentiating a pancreatic neoplasm in a patient with pancreatitis can be challenging due to their similar presentations. A 57-year-old African American man with a history of congestive heart failure, pancreatitis, and incomplete pancreas divisum presented with an epigastric abdominal pain that radiated to his back. Imaging showed necrotizing pancreatitis, a developing splenic infarct, and a mass at the pancreas tail. The patient was discharged with pain medications and was recommended follow-up imaging after resolution of his pancreatitis. He was readmitted to the emergency department 2 weeks later with recurrent acute abdominal pain. Computed tomography scan of abdomen and pelvis followed by magnetic resonance imaging and endoscopic ultrasound revealed an infiltrative pancreatic tail mass. Biopsy of the mass confirmed a locally advanced pancreatic tail adenocarcinoma. Chronic pancreatitis is associated with pancreatic cancer. Practitioners should be aware of the co-existence of chronic pancreatitis and pancreatic cancer, and the initial steps to evaluate a malignancy in chronic pancreatitis.

Bleeding and thrombotic events in bevacizumab-treated patients with colorectal cancer on novel oral anticoagulants and antiplatelet medications.

Background: Bevacizumab is a humanized monoclonal anti-VEGF antibody often given in combination with fluorouracil-based chemotherapy as therapy for metastatic colorectal cancer (mCRC). The bleeding and thrombotic event rates in the setting of concurrent novel oral anticoagulants with and without aspirin and bevacizumab treatment in patients with mCRC remain unclear. Methods: 462 patients with mCRC at Barnes-Jewish Hospital were identified between December 1, 2016 and December 1, 2021 and screened for concurrent treatment with bevacizumab and anticoagulant or antiplatelet therapy. Demographic and clinical information was extracted by electronic chart review. Results: 21 patients were identified who received bevacizumab and either apixaban or rivaroxaban for mCRC treatment. Aspirin was prescribed in some of these patients within three years of starting apixaban or rivaroxaban. Of the 13 patients without aspirin prescription, nine were given apixaban, and four were given rivaroxaban while on bevacizumab. Four out of nine of the patients who received apixaban had epistaxis, and only one case resulted in any treatment discontinuation. Three out of four of the patients who received rivaroxaban experienced bleeding, and one of these three patients discontinued bevacizumab. We also looked at eight patients who had received aspirin. Two out of seven patients who received apixaban/bevacizumab/aspirin experienced bleeding and discontinued a medication. The patient who received rivaroxaban/bevacizumab/aspirin experienced bleeding and discontinued bevacizumab. No patient experienced adverse thrombotic events. Conclusions: Patients with mCRC treated with bevacizumab and apixaban with no history of aspirin use within three years have a relatively low risk of bleeding that warrants treatment discontinuation.