Monitoring molecular-specific pharmacodynamics of rapamycin in vivo with inducible Gal4->Fluc transgenic reporter mice.

Rapamycin (Rap), a small-molecule inhibitor of mTOR, is an immunosuppressant, and several Rap analogues are cancer chemotherapeutics. Further pharmacologic development will be significantly facilitated if in vivo reporter models are available to enable monitoring of molecular-specific pharmacodynamic actions of Rap and its analogues. Herein we present the use of a Gal4→Fluc reporter mouse for the study of Rap-induced mTOR/FKBP12 protein-protein interactions in vivo with the use of a mouse two-hybrid transactivation strategy, a derivative of the yeast two-hybrid system applied to live mice.

Advances in bioluminescence imaging of live animal models.

Many of the obligate steps of physiology and disease are dynamic in time and space, and thus, end-point assays do not always provide a full understanding of these processes. Comprehensive understanding of the functional complexity of protein interactions and cell trafficking requires mapping of cellular and molecular function within complex systems over biologically relevant time scales. New approaches to bioluminescence imaging of cell migration, signaling pathways, drug action, and interacting protein partners in vivo allow the study of biology and disease within the context of living animals.

Development of an optimized activatable MMP-14 targeted SPECT imaging probe.

Matrix metalloproteinase-14 (MT1-MMP or MMP-14) is a membrane-associated protease implicated in a variety of tissue remodeling processes and a molecular hallmark of select metastatic cancers. The ability to detect MMP-14 in vivo would be useful in studying its role in pathologic processes and may potentially serve as a guide for the development of targeted molecular therapies. Four MMP-14 specific probes containing a positively charged cell penetrating peptide (CPP) d-arginine octamer (r(8)) linked with a MMP-14 peptide substrate and attenuating sequences with glutamate (8e, 4e) or glutamate-glycine (4eg and 4egg) repeating units were modeled using an AMBER force field method.

Biodistributions of 177Lu- and 111In-labeled 7E11 antibodies to prostate-specific membrane antigen in xenograft model of prostate cancer and potential use of 111In-7E11 as a pre-therapeutic agent for 177Lu-7E11 radioimmunotherapy.

Introduction: Prostate-specific membrane antigen is a transmembrane glycoprotein highly expressed in many prostate cancers and can be targeted with radiolabeled antibodies for diagnosis and treatment of this disease. To serve as a radioimmunotherapeutic agent, a kinetically inert conjugate is desired to maximize tumor uptake and tumor radiation dose with minimal nonspecific exposure to bone marrow and other major organs.

Materials And Methods: In this study, we assessed the pharmacokinetics and biodistribution of the 7E11 monoclonal antibody (MAb) radiolabeled with the lutetium-177 ((177)Lu)-tetraazacyclododecanetetraacetic acid conjugate system ((177)Lu-7E11) versus those of the 7E11 MAb radiolabeled with the indium-111 ((111)In)/glycyl-tyrosyl-(N,-diethylenetriaminepentaacetic acid)/lysine hydrochloride conjugate system ((111)In-7E11, also known as ProstaScint) to determine the feasibility of using (111)In-7E11 as a pre-therapeutic agent for (177)Lu-7E11 radioimmunotherapy.

Early detection of splenic metastasis of lung cancer by 18F-2-fluoro-2-deoxyglucose positron emission tomography.

Diagnosis of splenic involvement by lung cancer in the early stage is helpful for introducing proper treatment. We report a case of pulmonary adenocarcinoma with splenic metastasis which was first detected by 18F-2-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET). This 56-year-old male underwent left pneumonectomy, extensive lymph node dissection and postoperative adjuvant chemotherapy and radiotherapy.

Early restaging whole-body (18)F-FDG PET during induction chemotherapy predicts clinical outcome in patients with locoregionally advanced nasopharyngeal carcinoma.

Purpose: This study was undertaken to evaluate the utility of whole-body (18)F-FDG PET in monitoring therapeutic effect during induction chemotherapy (IC) and in predicting prognosis in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

Methods: Fifty patients who had histologically proven, locoregionally advanced NPC without distant metastasis and had received IC were recruited in this study. The study cohort consisted of 19 females and 31 males (age 17-72 years, mean 45.

Biliary hamartomas with delayed 99mTc-diisopropyl iminodiacetic acid clearance.

We report a 61-year-old asymptomatic man who had a hepatic lesion whose nature was undetermined, based on biochemistry, serology, ultrasonography, computed tomography, and magnetic resonance imaging studies. Biliary hamartomas were diagnosed by echo-guided needle biopsy. Functional studies of bile excretion, using 99mTc-diisopropyl iminodiacetic acid (99mTc-DISIDA) scintigraphy liver single-photon emission computed tomography (SPECT) showed the delayed transit of tracers from hepatocytes to the biliary hamartomas and the delayed emptying of tracers to the neighboring bile ducts.

Whole-body 18F-FDG PET in recurrent or metastatic nasopharyngeal carcinoma.

Unlabelled: The aim of this retrospective study was to evaluate the sensitivity and prognostic significance of whole-body (18)F-FDG PET for nasopharyngeal carcinoma (NPC) patients for whom there was a suspicion of recurrence or metastasis by conventional radiologic or clinical findings during their follow-up examinations.

Methods: Whole-body (18)F-FDG PET examinations were performed on 64 Taiwanese NPC patients (14 female, 50 male; mean age +/- SD, 45.8 +/- 13.

Using 18-fluoro-2-deoxyglucose positron emission tomography in detecting infectious endocarditis/endoarteritis: a preliminary report.

Rationale And Objectives: We evaluated the effectiveness of positron emission tomography (PET) with 18-fluoro-2-deoxyglucose (FDG) in the detection of infectious endocarditis/endoarteritis.

Materials And Methods: For this study, we recruited 6 patients (4 women, 2 men; age range, 35 - 78 years; mean age, 55.8 +/- 16.

18-fluoro-2-deoxyglucose positron emission tomography in detecting residual/recurrent nasopharyngeal carcinomas and comparison with magnetic resonance imaging.

Background: It is known that 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is effective in the early detection of residual/recurrent nasopharyngeal carcinomas (NPC). To compare FDG-PET with the conventional magnetic resonance imaging (MRI) for the detection of residual/recurrent NPC, the authors studied 67 follow-up cases of patients with NPC using both FDG-PET and MRI.

Methods: From February 1997 to February 2001, 67 NPC patients (14 women, 53 men; age range, 16-67 years; mean age, 46.