Human transferrin receptor gene as a marker gene for MR imaging.

PURPOSE: To quantitate and characterize the expression of an engineered human transferrin receptor (ETR) as a marker gene by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: Rat gliosarcoma 9L cells stably expressing ETR (ETR+) were used, with nontransfected (ETR-) cells serving as controls. A conjugate of transferrin and monocrystalline iron oxide (Tf-MION) nanoparticles was synthesized to probe for the activity of ETR. Accumulation of Tf-MION was examined by using cell internalization in culture and MR (n = 6) and nuclear (n = 4) imaging in a mouse model with ETR+ and ETR- tumors implanted in the opposite flanks. Autoradiographic and histopathologic results were correlated with MR findings. RESULTS: Tf-MION was internalized by ETR+ cells at 37 degrees C but not at 4 degrees C. Rhodamine-labeled Tf-MION and fluorescein-labeled antibody to ETR colocalized in small vesicle-like structures in the cytoplasm. Both findings were consistent with accumulation by the receptor-mediated endocytosis mechanism of ETR. Compared with ETR- tumors, ETR+ tumors accumulated more Tf-MION and had higher signal intensity on T1-weighted MR images and lower signal intensity on T2-weighted images. Autoradiographic findings showed a spatial correlation between MR signal intensity and TF-MION accumulation. CONCLUSION: ETR+ tumors internalize the MR imaging probe through the action of transferrin receptor in amounts that can be detected with MR imaging.

Macrocyclic chelators with paramagnetic cations are internalized into mammalian cells via a HIV-tat derived membrane translocation peptide.

A major obstacle to using paramagnetic MR contrast agents for in vivo cell tracking or molecular sensing is their generally low cellular uptake. In this study, we show that a paramagnetically labeled DOTA chelator derivatized with a 13-mer HIV-tat peptide is efficiently internalized into mammalian cells. Intracellular concentrations were attained that were readily detectable by MR imaging using both gadolinium and dysprosium chelates. Using this paradigm, it should be feasible to internalize a variety of chemically different agents into mammalian cells.

Screening admission CT scans in patients with AIDS--a randomized trial.

OBJECTIVE: To determine if the length of hospital stay could be reduced for patients with AIDS by performing screening head and abdominal-pelvic computed tomography (CT) scans within 24 hours of admission, regardless of presenting signs and symptoms. DESIGN: Randomized, prospective trial. SETTING: Tertiary, academic medical center. PATIENTS: On presentation to the emergency department, 42 patients with AIDS were identified as being eligible to participate in our study. Twenty-two patients consented to participate and were assigned to screening CT or control group. INTERVENTION: Patients assigned to the screening CT group had head and abdominal-pelvic CT scans within 24 hours of admission, regardless of presenting signs or symptoms. The findings of the screening CT scans were immediately communicated to the patient's referring physician. Patients assigned to the control group had CT studies done solely at the discretion of their physician. MAIN OUTCOME MEASURE: Length of stay for patients in the screening CT and control groups. RESULTS: The average length of stay for patients in the screening CT group was 1.3 days longer than the average length of stay for patients in the control group (95% CI, 1.4 days shorter to 4 days longer). The study was terminated after 22 patients were enrolled. CONCLUSION: Screening CT scans of the head and abdomen and pelvis at the time of hospital admission do not reduce the length of stay for patients with AIDS.