André Luís Branco de Barros

Bombesin derivative radiolabeled with technetium-99m as agent for tumor identification.

A bombesin derivative was successfully radiolabeled in high labeling yield. Biodistribution studies and scintigraphic images in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle and tumor-to-blood ratios. Thus, (99m)Tc-HYNIC-Bombesin((7-14)) could be used as an agent for tumor diagnosis.

Liposomes radiolabeled with 159Gd: In vitro antitumoral activity, biodistribution study and scintigraphic image in Ehrlich tumor bearing mice

PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the Gd-DTPA-BMA complex were prepared and radiolabeled by neutron activation. The radiolabeled liposomes presented significant in vitro cytotoxic activity against Ehrlich tumor cells when compared with controls. The biodistribution profile of these liposomes and free (159)Gd-DTPA-BMA were studied in mice bearing a previously-developed solid Ehrlich tumor. The results demonstrated an important uptake of the formulations by the tumor tissue, with a tissue/blood partition coefficient (Kp) 3.88 and 14.16 times higher than that of the free complex for pH-sensitive PEG-coated and PEG-folate-coated liposomes containing the (159)Gd-DTPA-BMA complex, respectively. Both formulations accumulated in the liver and spleen, thereby revealing some difficulty in escaping the action of the MPS cells. The formulation without folate presented a lower renal uptake, which is desirable in patients with chronic renal failure due to the potential risk of nephrogenic systemic fibrosis (NFS). The scintigraphic study revealed that the target/non-target ratio is always greater than three for pH-sensitive PEG-coated liposome formulations and above nine for pH-sensitive PEG-folate-coated liposome formulations. The results obtained in this study demonstrated that the formulations employed can be considered to be a potential alternative for the treatment of cancer, including patients with chronic renal failure.

Synthesis and biodistribution studies of carbohydrate derivatives radiolabeled with technetium-99m

Three carbohydrate derivatives, MAG(3)-Gl, MAG(3)-Ga, MAG(3)-NG, were synthesized and radiolabeled in high yields. These substances were injected in health Swiss mice and their biodistribution were evaluated. Among them, (99m)Tc-MAG(3)-Ga displayed higher accumulation in hepatic tissue, due to the presence of specific receptors in the liver for this carbohydrate. Thus, the use of (99m)Tc-MAG(3)-Ga to assess hepatic function can be considered.

A novel d-glucose derivative radiolabeled with technetium-99m: Synthesis, biodistribution studies and scintigraphic images in an experimental model of Ehrlich tumor

A d-glucose-MAG(3) derivative was successfully synthesized and radiolabeled in high labeling yield. Biodistribution studies and scintigraphic images in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Thus, d-glucose-MAG(3) could be considered as agent for tumor diagnosis.

Synthesis, characterization, and biodistribution studies of (99m)Tc-labeled SBA-16 mesoporous silica nanoparticles.

Along with anti-cancer drug delivery researches, many efforts have been done to develop new tracers for diagnostic applications. Based on advances in molecular imaging, nanoparticles can be used to visualize, characterize and measure biological process at molecular and cellular level. Therefore, the purpose of this study was to synthesize, characterize and radiolabeled mesoporous silica nanoparticles (MSNs) for in vivo applications. The nanoparticles were synthesized, functionalized with 3-aminopropyltriethoxysilane (APTES) and then, anchored with diethylenetriaminepentaacetic acid (DTPA). Particles were physicochemical characterized by elemental analysis (CHN), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and zeta potential, and were morphologically characterized by scanning electron microscopy (SEM), low-angle X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. Results indicate that functionalization process was successfully achieved. Next, functionalized silica nanoparticles were radiolabeled with technetium-99m showing high radiochemical yields and high radiolabeled stability. These findings allow the use of the particles for in vivo applications. Biodistribution and scintigraphic images were carried out in healthy mice in order to determine the fate of the particles. Results from in vivo experiments showed high uptake by liver, as expected due to phagocytosis. However, particles also showed a significant uptake in the lungs, indicated by high lung-to-non-target tissue ratio. In summary, taking into account the great potential of these silica mesoporous structures to carry molecules this platform could be a good strategy for theranostic purposes.

Functionalized single-walled carbon nanotubes: cellular uptake, biodistribution and applications in drug delivery

The unique properties of single-walled carbon nanotubes (SWNTs) enable them to play important roles in many fields. One of their functional roles is to transport cargo into cell. SWNTs are able to traverse amphipathic cell membranes due to their large surface area, flexible interactions with cargo, customizable dimensions, and surface chemistry. The cargoes delivered by SWNTs include peptides, proteins, nucleic acids, as well as drug molecules for therapeutic purpose. The drug delivery functions of SWNTs have been explored over the past decade. Many breakthrough studies have shown the high specificity and potency of functionalized SWNT-based drug delivery systems for the treatment of cancers and other diseases. In this review, we discuss different aspects of drug delivery by functionalized SWNT carriers, diving into the cellular uptake mechanisms, biodistribution of the delivery system, and safety concerns on degradation of the carriers. We emphasize the delivery of several common drugs to highlight the recent achievements of SWNT-based drug delivery.

Tumor bombesin analog loaded long-circulating and pH-sensitive liposomes as tool for tumor identification

Long-circulating and pH-sensitive liposomes trapping (99m)Tc-HYNIC-βAla-bombesin((7-14)) (aSpHL-(99m)Tc-BBN((7-14))) were successfully prepared. Biodistribution studies and scintigraphic images were performed in Ehrlich tumor-bearing Swiss mice. This system showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Therefore, aSpHL-(99m)Tc-BBN((7-14)) could be considered as a potential agent for tumor diagnosis.

Synthesis and biological evaluation of technetium-labeled D-glucose-MAG3 derivative as agent for tumor diagnosis.

A d-glucose-MAG(3) derivative was successfully synthesized and radiolabeled in high labeling yield. Biodistribution studies in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle ratio and moderate tumor-to-blood ratio. Thus, d-glucose-MAG(3) is a potential agent for tumor diagnosis.

Aptamers directly radiolabeled with technetium-99m as a potential agent capable of identifying carcinoembryonic antigen (CEA) in tumor cells T84.

Aptamers are small oligonucleotides that are selected to bind with high affinity and specificity to a target molecule. Aptamers are emerging as a new class of molecules for radiopharmaceutical development. In this study a new method to radiolabel aptamers with technetium-99m ((99m)Tc) was developed. Two aptamers (Apt3 and Apt3-amine) selected against the carcinoembryonic antigen (CEA) were used. Labeling was done by the direct method and the developed complex was subjected to quality control tests. Radiochemical purity and stability were monitored by Thin Layer Chromatography. Binding and specificity assays were carried out in the T84 cell line (CEA+) to evaluate tumor affinity and specificity after radiolabeling. Aptamers were successfully labeled with (99m)Tc in high radiochemical yields, showing in vitro stability in presence of plasma and cystein. In binding assays the radiolabeled aptamer Apt3-amine showed the highest affinity to T84 cells. When evaluated with HeLa cells (CEA-), lower uptake was observed, suggesting high specificity for this aptamer. These results suggest that the Apt3-amine aptamer directly labeled with (99m)Tc could be considered a promising agent capable of identifying the carcinoembryonic antigen (CEA) present in tumor cells.

Kit formulation for 99mTc-labeling of HYNIC-βAla-Bombesin((7-14)).

Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors. Several forms of cancer, including lung, prostate, breast, and colon express receptors for bombesin-like peptides. Radiolabeled BBN analogs with a high affinity for these receptors might be used for scintigraphic imaging. Kit formulations for labeling these molecules are important for routine preparation. A freeze-dried kit for labeling HYNIC-βAla-Bombesin((7-14)) with technetium-99m was prepared, and its storage stability was evaluated by in vitro and in vivo assays.