The Preparation, Biodistribution, and Dosimetry of Encapsulated Radio-Scandium in a Dendrimer for Radio-nano-pharmaceutical Application.

This study aimed to investigate the synthesis, characterization, and biodistribution of scandium nanoparticles encapsulated within poly (amidoamine) (PAMAM) dendrimers, as well as to estimate the human absorbed dose. It also aimed to examine, in particular, the amine-terminated PAMAM dendrimers in generation 5. Irradiation of the compound in the nuclear reactor resulted in the formation of Sc-radioactive complex nanoparticles. The compound of the dendrimer-Sc3+ was confirmed by the UV-vis spectrometer. The size of the particles was less than 10 nm, and it was assessed using high-resolution transmission electron microscopy (HRTEM) and dynamic light scattering (DLS). The synthesized complex was irradiated by the 3 × 1011 n.cm-2s-1 flux of neutron for 2 h. Mice bearing a breast tumor were employed to assess the therapeutic dose that was delivered by the poly scandium-46-nanoparticles. As opposed to the untreated groups, a single injection of poly phosphate-buffered saline to intratumoral in other groups to deliver a dose of 100 µCi resulted in a statistically significant 39.24% reduction in tumor volume 14 days after injection. After applying the biokinetics data in mice, the human's absorbed dose from scandium-47 encapsulated PAMAM was extrapolated based on animal data. The absorbed doses in critical organs, including the liver, lung, spleen, kidney, and bone, were 0.879, 0.0472, 0.191, 0.107, and 0.155 mGy/MBq, respectively.

DEVELOPMENT AND ESTIMATION OF HUMAN DOSIMETRY OF A NEW 47SC-RISEDRONATE FOR RADIOPHARMACEUTICAL APPLICATION.

Bisphosphonate risedronate (2-(3-pyridinyl)-1-hydroxyethane diphosphonic acid) was radiolabeled with scandium-47 (47Sc) as potential therapeutic radiopharmaceutical for skeletal metastases. Its time-dependent biodistribution in mice was measured and its human dosimetry was derived. The labelling process was performed at 95 °C for 30 min. The stability of the radio-conjugate was tested in human serum at 37 °C and its biodistribution was studied in balb/c mice. The radiochemical yield of ≥90% was obtained corresponding to a specific activity of 277 MBq/mg. The radio-conjugate showed good stability in human serum up to 48 h. A high bone uptake by 48 h post-injection was achieved, which suggests that 47Sc-risedronate may be therapeutically beneficial for the palliation of painful bone metastasis. The estimated absorbed dose coefficient and the time-integrated activity coefficient (ã (rs, TD)) in the bone were 1.35 mGy/MBq and 31.04 (Bq-h/Bq), respectively. The absorbed doses to non-osseous normal organs were much lower than that to the bone.

The preparation, biodistribution, and human's absorbed dose evaluation of Radio-Scandium-HYNIC-TOC for somatostatin-receptor-positive neuroendocrine tumors therapy by animal study.

BACKGROUND: Most of the neuroendocrine tumors (NETs) express Somatostatin receptors (SSTr), which are the main bases for the development of several radiopharmaceuticals for therapy and imaging of these types of tumors. In this study, 46 Scandium nuclide was used to label a peptide compound via hydrazinonicotinyl-Tyr3-Octreotide (HYNIC-TOC) and researched further for somatostatin-receptor NETs treatment. METHODS AND MATERIALS: The labeling procedure was conducted at 95°C for 10 min. The compound stability was tested in the environment of human serum at 37°C. The biodistribution of compound was investigated in balb/c normal mice and mice bearing AR4-2J tumor. Absorbed Doses of Human Organs were estimated by extrapolation of the biokinetics data of compound in mice to human's organs and then the absorbed doses were estimated by application of MATLAB and MIRDOSE software. RESULTS: Labeling yield was more than 90% with 555 MBq/mg specific activity. The radio-labeled compound expressed well consistency in human serum. The tumor uptake reached 3.831 ID/g% until 4 h post-injection and increased to 5.564%ID/g until 24 h post-injection. CONCLUSION: The main achievement of this study was high tumor uptake of 46 Sc-HYNIC-TOC which may be therapeutically valuable for the therapy of NETs. The estimation of the absorbed dose of human from 47 Scandium-HYNIC-TOC showed low absorbed doses in critical organs and the elimination of the radiopharmaceutical was through the gastrointestinal tract.

Dosimetry of 175Ytterbium-poly (amidoamine) Therapy for Humans' Organs.

PURPOSE: This investigation focuses on biodistribution of irradiated dendrimer encapsulated ytterbium-175 (175Yb) and to estimate the absorbed dose from intravenous injection of PAMAM encapsulated 175Yb to human organs. METHODS: A dendrimer compound containing an average of 55 Yb+3 ions per dendrimer was prepared and irradiated with neutrons for 2h at 3×1011 n.cm-2s-1 neutron flux. The resulting mixture was injected into a group of tumor bearing mice and the mice were excised, weighed and counted at certain times to study the biodistribution. The human organs absorbed dose was assessed by MIRD schema and MCNP simulation. RESULTS: The specific activity and radiochemical purity of the irradiated nano-composite were 7MBq/mg and >99% respectively. The rapid up take of dendrimer was in liver, lung, and, spleen. MIRD and MCNPX were applied for dose estimation. The human absorbed dose in liver, lung, spleen, kidney and bone that simulated by MCNP are 1.266, 0.8081, 0.8347, 0.03979 and 0.01706 mGy/MBq respectively and these values for MIRD schema are 1.351, 0.73, 1.03, 0.039, and 0.0097 mGy/MBq respectively. CONCLUSION: The results showed that 175Yb-PAMAM nano-radiopharmaceutical has potential of application for liver and lung tumors.

Development of bone seeker radiopharmaceuticals by Scandium-47 and estimation of human absorbed dose.

In this study labeling EDTMP (ethylenediamine tetra(methylene phosphonic acid)) and HEDP (Hydroxyethylidene-1, 1-Diphosphonic Acid) as the carrier ligands with Scandium-47 were investigated. The biokinetics of the bone seeking of labeled ligands with Scandium-47 were assessed by measuring the skeletal absorbed dose and then the mice data extrapolated to human absorbed dose and compared with the 186/188Rhenium-HEDP, 153Samarium-EDTMP dosimetry data estimated by other researchers. Because the availability of 47Sc was limited we performed some preliminary studies using 46Sc.

Development of Dendrimer Encapsulated Radio-Ytterbium and Biodistributionin Tumor Bearing Mice.

The aim of this study is preparation of dendrimer encapsulated ytterbium-175 radio-nanoparticles and investigation of the compound chemical characteristic before and after the neutron irradiation and also study the in vivo biodistribution for targeted radiopharmaceutical dose delivery to solid tumors. For preparation of dendrimer-metal nanocomposite, a dendrimer compound containing an average of 55 Yb+3 ions per dendrimer was prepared. The synthesized encapsulated ytterbium irradiated by neutron for 2 h at 3×1011 n.cm [Formula: see text] neutron flux. The resulting mixture was injected into 2 separate groups of tumor bearing mice. One group were injected intravenously and the other group were injected directly in tumor and were excised, weighed and counted at certain times to study the biodistribution and to compare the tumor treatment and the leakage of the radiopharmaceutical to non-target organs. The formation of dendrimer-Yb3+complex was confirmed by UV-vis spectrometer. High-resolution transmission electron microscopy (HRTEM) and Dynamic Light Scattering (DLS) results showed a particle size of less than 10 nm. The specific activity and radio-ytterbium purity of the irradiated nano-composite were as follows: 7 MBq/mg and >95%. The measured radiochemical purity by Instant Thin Layer Chromatography (ITLC) was more than 99%. In intravenous injection the complex showed rapid up take in liver, spleen, and lung, while accumulation in other organs was insignificant. In tumor direct injection the average size of the tumor mass in mice was reduced by 30%.

Production and purification of Scandium-47: A potential radioisotope for cancer theranostics.

In this study, production of 47Sc radionuclide by irradiating the natural titanium dioxide powder (TiO2) in the fast neutron flux (~3*1013ncm-2s-1) for 4 days in Tehran Research Reactor (TRR, Iran) and separation from titanium target was investigated. The study showed the feasibility of production 47Sc by TRR. The separation efficiency and radiochemical purity (ScCl3) of radio-scandium, 47Sc radionuclide purity were obtained 98%, 99% and 88% respectively.

Production, biodistribution, and dosimetry of (47)Sc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid as a bone-seeking radiopharmaceutical.

In this study 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) was used as the polyaminophosphonic acid carrier ligand and the therapeutic potential of the bone seeking radiopharmaceutical (47)Sc-DOTMP was assessed by measuring its dosage-dependent skeletal uptake and then the absorbed radiation dose of human organs was estimated. Because of limited availability of (47)Sc we performed some preliminary studies using (46)Sc. (46)Sc was produced with a specific activity of 116.58 MBq/mg (3.15 mCi/mg) and radionuclide purity of 98%. (46)Sc-DOTMP was prepared and an activity of 1.258 MBq (34 µCi) at a chelant-to-metal ratio of 60:1 was administered to five groups of mice with each group containing 3 mice that were euthanized at 4, 24, 48, 96 and 192 h post administration. The heart, lungs, liver, spleen, kidneys, intestine, skin, muscle, and a femur were excised, weighed, and counted. The data were analyzed to determine skeletal uptake and source organ residence times and cumulated activities for (47)Sc-DOTMP. (46)Sc-DOTMP complex was prepared in radiochemical purity about 93%. In vitro stability of complex was evaluated at room temperature for 48 h. Biodistribution studies of complex in mice were studied for 7 days. The data were analyzed to estimate skeletal uptake and absorbed radiation dose of human organs using biodistribution data from mice. By considering the results, (47)Sc-DOTMP is a possible therapeutic agent for using in palliation of bone pain due to metastatic skeletal lesions from several types of primary cancers in prostate, breast, etc.