99mTc Stearyl 6-(benzylidenehydrazinyl) nicotinamide Liposomes as Tumor Permeability Evaluation Tracer.

Nanomedicine is a highly demanded discipline. Liposomes have seen an increased attention due to their physicochemical properties that allow them to act as nanocarriers of drugs and also of radioisotopes that can be used to diagnose and treat cancer. In order to obtain a novel permeability cancer imaging agent based on 99mTc-labeled liposomes, we describe microwave-assisted synthesis of stearyl 6-(benzylidenehydrazinyl) nicotinamide lipid, which was included in two formulations: nanometric hydrazinonicotinic acid (HYNIC) liposome and its PEGylated coated analogue, HYNIC-PEG liposome. Radiolabeling with 99mTc via stearyl 6-(benzylidenehydrazinyl) nicotinamide was found to be easy, reproducible, and stable, revealing high radiochemical purity (94 ± 1.7%) for both liposomal formulations. Biodistribution at 4 h and 24 h and scintigraphic images at 4 h were performed in normal and melanoma-bearing C57BL/6 mice. Biodistribution studies at 4 h showed tumor uptake of 99mTc-HYNIC liposome and 99mTc-HYNIC-PEG liposome (1.1 ± 0.6 and 2.5 ± 0.4, respectively) and also at 24 h p.i. (1.8 ± 0.5 and 3.0 ± 1.1, respectively). Scintigraphic images showed appreciable tumor uptake in melanoma tumor-bearing mice with both liposomal formulations. Our results show that 99mTc stearyl 6-(benzylidenehydrazinyl) nicotinamide liposomes can be used as diagnostic noninvasive in vivo tumor-targeting agents capable of evaluating tumor permeability and development who can be used in personalized chemotherapy planning.

(99m)Tc glucarate as a potential radiopharmaceutical agent for assessment of tumor viability: from bench to the bed side.

Several radiotracers have been used for assessing cell death, whether by necrosis or apoptosis. (99m)Tc glucarate, which has initially been reported to be concentrating/accumulating in myocardial infarction or zones of cerebral injury, has also shown some tumor-seeking properties in a few preliminary studies. Under International Atomic Energy Agency (IAEA)'s coordinated research program, we report here the standardization, quality control, and clinical evaluation (detection, evaluation of response, and comparison with (18)F Fluorodeoxyglucose) of this tracer in well-characterized lung cancer and head neck malignancies in a single-arm prospective observational study. Forty-seven patients (29 inoperable lung carcinoma and 18 head and neck malignancies) were prospectively enrolled and underwent (99m)Tc glucarate imaging [whole body planar and single-photon emission computed tomography of the region of interest] 4-5 hours after injection of 20 mCi of the radiopharmaceutical. Excellent (99m)Tc glucarate concentration was noted in the target lesion in lung cancer and head and neck malignancies. The sensitivity was found to be better in lung cancer. Avid concentration of tracer was seen in the metastatic sites. During response evaluation, the glucarate concentration correlated well with the clinical and other radiological findings. (99m)Tc glucarate showed avid concentration of tracer in the tumor, suggesting it to be a potential tumor imaging agent which can be used for detection and assessment of therapeutic response in malignancy.

Membrane and circuit properties of lateral septum neurons: relationships with hippocampal rhythms.

The lateral septum receives the most important afferents from the hippocampus, has been proposed to contribute to theta (theta) rhythm generation. Our aim was to study the membrane and circuital properties of lateral septum neurons and their relationship with hippocampal rhythms. Extra- and intracellular recordings (n=81) were obtained in urethane-anesthetized rats. Two neuronal populations were found, one of them with hippocampal theta; rhythm dependence (theta-D, 68%), and the other group independent of hippocampal theta; rhythm (theta-I, 32%). Other differences were spontaneous firing rate (theta-D=13.20+/-2.09, theta-I=6.99+/-1.18; p<0.005) with a bursting pattern in the theta-D group and single discharges in the theta-I group. Intracellular recordings showed higher synaptic activity in theta-D than in theta-I neurons. Both groups showed fast spikes while only theta-D neurons had high-threshold and low-threshold slow spikes. theta-D neurons had theta-oscillations in their membrane potential. Stimulation of the contralateral lateral septum resets the hippocampal theta rhythm and the theta rhythm recorded intracellularly in the lateral septum neurons. Some neurons (10.6%) showed rhythmic oscillations lasting a few seconds, at a higher frequency than those of the simultaneously recorded hippocampal EEG. This high frequency appeared spontaneously or could be evoked by stimulations of the fornix and reticularis pontis oralis nucleus (RPO). Homologous high frequency oscillations appeared in the simultaneously recorded hippocampal EEG, synchronized with the neuronal activity, during fornix stimulation. RPO stimulation evoked increments (57%) or decrements (43%) in the firing rate of lateral septum neurons. Thus, they could participate in different septal networks to modulate the theta rhythm. The marked functional relationship between lateral septum neurons and hippocampal theta rhythm supports the proposal that lateral septum represents a feedback system for the improvement of medial septum theta rhythm. The hypothalamic projections could be a way to introduce theta and higher rhythms into this structure that control many biological rhythms.