Decorated Superparamagnetic Iron Oxide Nanoparticles with Monoclonal Antibody and Diethylene-Triamine-Pentaacetic Acid Labeled with Thechnetium-99m and Galium-68 for Breast Cancer Imaging.

PURPOSE: In this study we developed and tested an iron oxide nanoparticle conjugated with DTPA and Trastuzumab, which can efficiently be radiolabeled with 99m-Tc and Ga-68, generating a nanoradiopharmaceutical agent to be used for SPECT and PET imaging. METHODS: The production of iron oxide nanoparticle conjugated with DTPA and Trastuzumab was made using phosphorylethanolamine (PEA) surface modification. Both radiolabeling process was made by the direct radiolabeling of the nanoparticles. The in vivo assay was done in female Balb/c nude mice xenografted with breast cancer. Also a planar imaging using the radiolabeled nanoparticle was performed. RESULTS: No thrombus and immune response leading to unwanted interaction and incorporation of nanoparticles by endothelium and organs, except filtration by the kidneys, was observed. In fact, more than 80% of 99mTc-DTPA-TZMB@Fe3O4 nanoparticles seems to be cleared by the renal pathway but the implanted tumor whose seems to increase the expression of HER2 receptors enhancing the uptake by all other organs. CONCLUSION: However, even in this unfavorable situation the tumor bioconcentrated much larger amounts of the nano-agent than normal tissues giving clear enough contrast for breast cancer imaging for diagnostics purpose by both SPECT and PET technique. Graphical Abstract ᅟ.

New chalcone compound as a promising antileishmanial drug for an old neglected disease: Biological evaluation using radiolabelled biodistribution.

OBJECTIVES: Treatment of leishmaniasis remains a challenge, especially due to the need for multiple painful injections, the toxicity of current drugs against the disease, their lack of efficacy and, lately, drug resistance. The aim of this study was to demonstrate the biological behaviour of 3-nitro-2'-hydroxy-4',6'-dimethoxychalcone (CH8) in a murine model of cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). METHODS: To evaluate its biological behaviour, compound CH8 was radiolabelled with technetium-99m (99mTc) using the direct reaction. Groups of animals infected with ether Leishmania infantum (as a model for VL) or Leishmania amazonensis (as a model for CL) were administered CH8-99mTc orally or subcutaneously, respectively, and its biodistribution was evaluated. RESULTS: Oral administration of CH8-99mTc resulted in poor absorption. However, the absorbed drug was expressively taken up in the blood and liver, the main organ infected in VL. CH8-99mTc administered by the subcutaneous route showed a poor distribution and significant uptake in the left ear, suggesting a local effect in the skin. In addition, the VL and CL infection models did not considerably alter the biodistribution profile by the oral and subcutaneous routes, respectively. CONCLUSION: These results suggest that CH8 is a promising candidate for oral treatment of VL and for intralesional treatment of CL, showing a prominent local effect.

Nano-Hydroxyapatite Doped with Ho-166 as Drug Delivery System for Bone Cancer Therapy and Diagnosis: Developing a Theragnostic Radiopharmaceuticals.

BACKGROUND: The use of nanobiomaterials is increasing each day. Among the immense variety of nanomaterials developed and studied the hydroxyapatite is one of the most ones. OBJECTIVE: In this study we developed and tested nano-hydroxyapatite dopped with Ho-166 for bone cancer. RESULTS: The results showed that the nano-hydroxyapatite dopped with Ho-166 has a great affinity for the bone. CONCLUSION: The pre-clinical studies support the use as a nano-radiopharmaceuticals for bone cancer treatment and diagnosis.

Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.

Drug delivery systems are under intense investigation all around the world, especially in oncology research. Indeed, in some cases, like bone metastasis, nanodrugs may represent the last and best choice for both treatment and imaging of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as radiopharmaceuticals for many years; however, their use as nanoradiopharmaceuticals is very innovative and creates a new way to establish radiopharmacy in this new scenario offered by nanotechnology. In this study we developed and tested nano-MDP-labelled with 99mTc in rats induced with bone cancer metastasis and the results showed that it may work in patients. However, some further experiments are required in order to initiate protocols in humans.

In vivo studies: comparing the administration via and the impact on the biodistribution of radiopharmaceuticals.

The use of in vivo assay to determine the biodistribution and subsequent inter-comparison with human parameters has been used since the dawn of science. The use of this type of test admits the metabolic equity among animals for inter-comparison. Thus, the use of Wistar rats in particular is quite frequent. Regarding routes of administration, there are three ways to test priority: jugular vein, intraocular (eye plexus) and caudal; there is a consensus that these three pathways behave in the same way, or at least very similar. Biodistribution studies of drugs, especially radiopharmaceuticals, have been using randomly any of these pathways believed to be effective in their likeness without worrying about your real analytic equity. In this study, we performed in vivo assay in 8 Wistar rats using 99mTc -labeled Herceptin to review the route of administration on the biodistribution result. Thus, four mice were injected via the intraocular (eye plexus), and four were injected via tail (caudal plexus). The results were quite disparate and call the attention of the scientific community to reassess the protocols for animal experiments, in order to have uniformity and fairness between the data and may represent a test for human inter-comparison of more reliable and trustworthy way.

Monoclonal antibodies: application in radiopharmacy.

In this study was carried on a systematic review of the data was carried out in the topic of monoclonal antibodies in the last 40 years. All the data collected and summarized revealed that this new class of medicine may bring great advance in the field of radiopharmacy, oncology and imaging.

Polymeric nanoparticles of FMISO: are nano-radiopharmaceuticals better than conventional ones?

Nanotechnology has been the last frontier in the diagnoses and treatment of many diseases, especially in oncology. The use of nanoparticles of radiopharmaceuticals may represent the future of Nuclear Medicine. In this study we developed, characterized and tested polymeric nanoparticles of FMISO (fluoromisonidazole) in a dynamic study of biodistribution. The results of the development as characterization showed that nanoparticles were well obtained with a size range of 300- 500 nm and a spherical shape.

Radiolabeling of cramoll 1,4: evaluation of the biodistribution.

The cramoll 1,4 is a well-studied lectin. However, few studies about its biodistribution have been done before. In this study, we radiolabeled the cramol 1,4 with Tc-99m and analyzed the biodistribution. The results showed that the cramol has an abnormal uptake by the bowel with reflections on its clearance mechanism.