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1.
J Med Chem ; 66(15): 10604-10616, 2023 08 10.
Article in English | MEDLINE | ID: mdl-37462154

ABSTRACT

Antibodies conjugated with diagnostic/therapeutic radionuclides are attractive options for inoperable cancers lacking accurate imaging methods and effective therapeutics, such as pancreatic cancer. Hence, we have produced an antibody radionuclide conjugate termed TE-1132 comprising a α-CA19-9 scFv-Fc that is site-specifically conjugated at each C-terminus to 3 DOTA chelators via a cysteine-containing peptide linker. The smaller scFv-Fc size facilitates diffusivity within solid tumors, whereas the chelator-to-antibody ratio of six enabled 177Lu-radiolabeled TE-1132 to exhibit high radioactivity up to 520 MBq/nmol. In mice bearing BxPC3 tumors, immuno-SPECT/CT imaging of [111In]In-TE-1132 and the biodistribution of [177Lu]Lu-TE-1132 showed selective tumor accumulation. Single and multiple doses of [177Lu]Lu-TE-1132 effectively inhibited the BxPC3 tumor growth and prolonged the survival of mice with no irreversible body weight loss or hematopoietic damage. The adequate pharmacokinetic parameters, prominent tumor accumulation, and efficacy with good safety in mice encourage the further investigation of theranostic TE-1132 for treating pancreatic cancer.


Subject(s)
Immunoconjugates , Pancreatic Neoplasms , Mice , Animals , Chelating Agents , CA-19-9 Antigen , Tissue Distribution , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/drug therapy , Radiopharmaceuticals/pharmacokinetics , Cell Line, Tumor , Lutetium , Pancreatic Neoplasms
2.
Medicine (Baltimore) ; 99(44): e23027, 2020 Oct 30.
Article in English | MEDLINE | ID: mdl-33126390

ABSTRACT

RATIONALE: Gout and gouty arthritis typically involve peripheral and monoarticular joints, especially the first metatarsophalangeal joint and knees. Hip involvement in patients with gout is rare, and its diagnosis is very difficult, especially in the late stages of the disease. Total hip arthroplasty could be a surgical treatment for atypical gouty arthritis of the hip; however, few cases have been reported. PATIENT CONCERNS: We reported an uncommon case of a 74-year-old man without typical symptoms of hip gout arthritis whom was misdiagnosed as having avascular necrosis of the femoral head. DIAGNOSES: Clinical examination and imaging revealed bilateral avascular necrosis of the femoral head. However, the final pathology report revealed left hip gout arthritis. INTERVENTIONS: The patient underwent left total hip arthroplasty and was followed up for 3years. OUTCOMES: The outcome was favorable. The function of the left hip was almost normal. LESSONS: Our case indicated the difficulty of the diagnosis of hip gout arthritis. Due to the lower rates of hip gout arthritis and lack of typical clinical examination, it is easy to misdiagnose. Furthermore, surgical treatment for the late stage of hip gout arthritis has not previously been reported. In our case, total hip arthroplasty proved to be a good option.


Subject(s)
Arthritis, Gouty/surgery , Hip Joint , Aged , Arthritis, Gouty/diagnostic imaging , Arthroplasty, Replacement, Hip , Diagnosis, Differential , Humans , Magnetic Resonance Imaging , Male
3.
Curr Pharm Des ; 26(3): 386-394, 2020.
Article in English | MEDLINE | ID: mdl-31880243

ABSTRACT

BACKGROUND: Postoperative delirium (POD), a neurobehavioral syndrome induced by dysfunction of neural activity, is a common and serious complication. This current study aimed to investigate independent predictors for POD in elderly subjects after total joint arthroplasty (TJA). METHODS: Eligible elderly patients (≥65 years) who underwent elective unilateral primary hip or knee arthroplasty under epidural anesthesia from October 2016 to January 2019 were consecutively enrolled. POD was diagnosed following the guidance of the 5th edition of Diagnostic and Statistical Manual of Mental Disorders, (DSM V, 2013). The relative change in serum Alb (ΔAlb) was defined as the absolute value of (preoperative Alb value- nadir value within postoperative day 2)/preoperative Alb ×100%. The predictive value of ΔAlb for POD was evaluated by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate logistic regression analyses were used for evaluating risk factors for POD. RESULTS: A total of 328 patients were enrolled in the analysis, of which 68 (20.7%, 68/328) patients developed POD within postoperative 7 days. ΔAlb was an effective predictor for POD with an area under the curve (AUC) of 0.821, a sensitivity of 76.15% and a specificity of 70.59%, respectively (P<0.001). Univariate and multivariate logistic regression analyses indicated that ΔAlb was the only independent risk factor for POD (OR: 2.43, 95%CI: 1.17-4.86, P=0.015). CONCLUSION: ΔAlb was an independent risk factor for POD in elderly subjects after TJA.


Subject(s)
Arthroplasty/adverse effects , Delirium , Postoperative Complications/diagnosis , Serum Albumin, Human/analysis , Aged , Delirium/blood , Delirium/diagnosis , Humans , Postoperative Complications/blood , Risk Factors
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