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 Table of Contents    
Year : 2015  |  Volume : 40  |  Issue : 3  |  Page : 156-164

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

1 Faculty of Nuclear Engineering and Physics, Amirkabir University of Technology, Tehran, Iran
2 Radiopharmaceutical Research and Development Lab (RRDL), Nuclear Science and Technology Research Institute (NSTRI), Postal Code: 14155-1339, Tehran, Iran

Date of Submission12-Aug-2015
Date of Decision27-Apr-2015
Date of Acceptance28-Apr-2015
Date of Web Publication11-Sep-2015

Correspondence Address:
Leila Moghaddam-Banaem
Radiopharmaceutical Research and Development Lab, Nuclear Science and Technology Research Institute, 14155-1339 Tehran
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Source of Support: Nil., Conflict of Interest: There are no conflicts of interest.

DOI: 10.4103/0971-6203.165078

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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 47Sc-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 47Sc we performed some preliminary studies using 46Sc. 46Sc was produced with a specific activity of 116.58 MBq/mg (3.15 mCi/mg) and radionuclide purity of 98%. 46Sc-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 47Sc-DOTMP. 46Sc-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, 47Sc-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.

Keywords: 47/46Sc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid, biodistribution, dosimetry, radiopharmaceuticals

How to cite this article:
Fathi F, Moghaddam-Banaem L, Shamsaei M, Samani A, Maragheh MG. Production, biodistribution, and dosimetry of 47Sc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid as a bone-seeking radiopharmaceutical. J Med Phys 2015;40:156-64

How to cite this URL:
Fathi F, Moghaddam-Banaem L, Shamsaei M, Samani A, Maragheh MG. Production, biodistribution, and dosimetry of 47Sc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid as a bone-seeking radiopharmaceutical. J Med Phys [serial online] 2015 [cited 2019 Apr 25];40:156-64. Available from:

   Introduction Top

A large percentage of cancer patients suffer from bone pain caused by bone metastases in the advanced stage of their diseases.[1],[2],[3],[4] One of the methods for therapy in these patients is systematic palliative therapy that uses suitable radionuclides linked to bone seeking ligands. This method has emerged the most effective treatment modality compared with other conventional methods such as the use of pain relieving drugs or radiotherapy with external sources for these patients, because this model has the most noticeable effect and minimal side-effects.[3],[4],[5],[6] The important factor in designing effective radiopharmaceuticals for palliative treatment of bone pain is to deliver sufficient radiation dose to bone lesions at skeletal surface and meanwhile minimize the radiation dose to the red bone marrow and normal tissues. Hence, an ideal radiopharmaceutical for palliative treatment should be selectively absorbed by the bone and concentrate in skeletal lesions, thereby delivering adequate dose at these lesion sites while minimizing radiation dose to the red bone marrow.[1],[3],[5] Researchers' results indicate that the radionuclides emit moderate or low energy β or conversion electron, are suitable candidates for attachment to bone seeking ligands and delivering effective absorbed dose to bones.[1],[3],[6]

47Sc is one of these suitable radioisotopes which has ability to link to bone-seeking ligands with short half-life of 3.47 days and has attracted attention for using in nuclear medicine in recent years.[2],[7],[8],[9],[10],[11],[12] 47Sc is a low β emitter (Eβ1Max = 0.600 MeV [32%], E β2 Max = 0.439 MeV [68%]) which emits a γ-ray at 0.159 MeV, therefore images could be obtained to assess bone target, document disease status, and predict therapeutic efficacy at the time of administering the therapeutic agent.[13] There are different nuclear reactions such as 47Ti(n, p) 47Sc and 46Ca (n, γ) 47Ca→ 47Sc for production of 47Sc in a reactor. The first reaction requires E n > 1 MeV and an enriched target, but the second reaction uses thermal neutrons. The disadvantage of the latter reaction is the requirement of an enriched target while presently 46Ca is available with only 30% enrichment and at a very high price. [10],[14],[15]Due to limited access to 47Sc, in this study and preliminary experiments, 46Sc radionuclide, which has similar chemical properties, was used. [2],[7],[8],[9],[11],[12] 46Sc with a long half-life (83.8 days) and one medium energy β and two γ-rays (EβMax = 0.3 MeV, Eγ = 1.12 MeV (100%), Eγ = 0.88)MeV (100%) can be produced simply by direct thermal neutron irradiation of natural 45 Sc and it is an ideal radionuclide for assessing the chemistry, stability, and biodistribution of scandium-labeled compounds. However, its long half-life and emission characteristics are unsuitable for clinical studies.[9],[13] Similar chemical properties have also resulted in similar activity bio-distribution and hence for dose calculations replacing the nuclear physical characteristics of 47Sc with those of 46Sc can be considered equivalent to 47Sc dosimetry.

In designing suitable radiolabeled agents for palliative bone pain, multidentate- polyamino-phosphonic acids such as 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetramethylene phosphonic acid (DOTMP) are found to be the most promising candidates as carrier ligands owing to their high bone affinity, selective localization in skeletal lesions and ability to form metal chelates with high in vivo stability [Figure 1].[3],[5] Based on the well-documented phenomenon DOTMP is a macrocyclic chelator that form thermo-dynamically more stable and kinetically more inert complexes with lanthanides and metals, compared to its acyclic analogs such as EDTMP.[1],[3],[6]
Figure 1: Structure of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid

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In the present paper, preparation of 46 Sc-DOTMP complex and its preliminary biological studies in animal models were studied. Then we evaluated the potential of 47 Sc-DOTMP to deliver 47 Sc to the skeletal surfaces of human by using MIRD formalism and considering to 46 Sc-DOTMP biodistribution data from mice. In nuclear medicine, MIRD formalism is the most commonly used method for the calculation and estimation of internal dose.[16]

   Experimental Top

Materials and methods

46Sc was produced with a specific activity of approximately 116.58 MBq/mg (3.15 mCi/mg) and radionuclide purity of >98% by irradiation of natural Sc2O3 target (0.73 mg) at a thermal neutron flux of approximately for 3 days at Tehran Research Reactor (TRR). DOTMP was purchased from Fluka Co. (Switzerland). Whatman No.1 paper was obtained from Whatman (Maidstone, UK) for instant thin layer chromatography (ITLC). All other chemical reagents were purchased from Merck (Darmstadt, Germany). Animal studies were performed in accordance with the United Kingdom Biological Council's Guidelines on the Use of Living Animals in Scientific Investigations, 2nd ed.[17] This study was performed using five groups of healthy male mice, each group containing 3 mice, with nominal weight of between 25 and 35 g which were purchased from Pasteur Institute, Tehran, Iran.

The radiopharmaceutical was injected into the tail vein of the mice. Following administration and at certain times, animals were sacrificed. The heart, lungs, liver, spleen, kidneys, intestine, urinary bladder, femur and the muscles surrounding the femur were dissected, weighed, and counted. A high purity germanium (HPGe) detector coupled with a Canberra™ (model GC1020-7500 SL) multichannel analyzer and a dose calibrator ISOMED 1010 (Dresden, Germany) were used for counting distributed activity in mice organs.

Production and radiochemical processing of 46Sc

46 Sc was produced by irradiation of natural Sc2O3 target at a thermal neutron flux of for a period of 48 h at the TRR. Following irradiation, the target was cooled for 8 days and subsequently dissolved in 3M HCl by gentle warming to prepare 46 ScCl3. The resultant solution was diluted to the appropriate volume with ultra-pure water, to produce a stock solution of final volume of 10 ml. The radionuclide purity of the solution and assay of the total activity produced was carried out by using HPGe spectroscopy. The total activity was obtained ~85.1 MBq (~2.3 mCi). The radiochemical purity of 46ScCl3 was evaluated by employing ITLC using (a) %10 ammonium acetate:methanol (1:1) mixture and (b) 10 mM/l diethylenetriaminepenta-acetic acid (DTPA).

Preparation and characterization of 46 Sc-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetramethylene phosphonic acid

2.2 ml of 46ScCl3 solution (18.5 MBq of 46Sc activity) was evaporated to near-dryness by slight warming 2 times. The 46Sc-DOTMP complex was prepared by adding 2.2 ml of 46ScCl3 solution to 80 mg of DOTMP and then dissolved in 1 ml of 0.5M NaOH buffer (metal to ligand ratio of 1:60). The pH of solution was adjusted to ~8 by adding another 2.2 ml of 0.5 M NaOH buffer. The mixture was gently heated for 10 min and then stirred in water bath with a temperature of 90° for 1 h. The radiochemical purity of 46Sc-DOTMP complex formed was determined by employing TLC using %10 ammonium acetate:methanol (1:1) mixture as the eluting solvents to discriminate free scandium from radiolabeled compound. For optimization of the labeling yield, experiments were carried out to determine the complexation yields of 46Sc-DOTMP at different ligand to metal ratios ranging between 20:1 and 60:1 by varying the ligand amount, while keeping the amount of 46Sc fixed at 0.35 mg.

In vitro stability studies

The in vitro stability of the 46Sc-DOTMP was studied by incubating the complex (prepared using 80 mg of DOTMP and 0.35 mg of 46 Sc) in pH ~8 at room temperature for a period of 48 h after preparation. The radiochemical purity of the complex was determined at regular time intervals by employing paper chromatography using %10 ammonium acetate:methanol (1:1) mixture and 10 mM/L DTPA as the eluting solvents and using standard quality control techniques.

Biodistribution studies in mice

Biodistribution study of 46 Sc-DOTMP complex was carried out in five groups of mice weighing between 25 and 35 g. Three ml (with 6.29 MBq/ml activity) of the complex solution were injected through the tail veins and the animals were sacrificed by suffocating in CO2 room at different intervals (4, 24, 48, 96 and 192 h) postinjection. From each group, one mouse was sacrificed at each time point. The tissues and the organs were excised and the activity associated with each organ/tissue was measured in gamma spectrometer with an HPGe detector. Distribution of the activity in different organs was calculated as decay corrected percentage of injected activity per gram (%ID/g). The skeletal and blood uptakes were calculated by assuming skeletal and blood weights to be 10% and 8% of the total body weight, respectively.[5],[18]

Estimated human dosimetry

The dose calculation and estimation was done for a certain group of organs of human following the MIRD technique, in which the absorbed dose, D, to a target organ (rk) is given in equation (1). In this equation, Ãh is the cumulated activity in the source region rk, S (rkrh) is the so-called S-value, which gives the dose in region rk per unit cumulated activity in source region rh, k is some proportionality constant which in MIRD formalism is 2.13, ϕi(rkrh) is fraction of energy emitted from source region rh that is absorbed in the target region rk, yi is number of radiation with energy Ei emitted per nuclear transition, Ei is energy per radiation and mrk is mass of target region.[19],[20]

As shown in equation (1), the S-values depend only on physical factor such as decay data of radioisotope and masses of the target regions, while Ãh depends only on biodistribution and retention of radiopharmaceutical in the body (f: Uptake fraction and Te: Effective half-life of radiopharmaceutical) and can be calculated in each organ according to equation (2) where Ãh is activity in source organ at time t and A0 is the activity administered to the body at time t = 0, and fs(t) is the fraction of administered activity present within the source region at time t and (τ) is residence time.[20],[21],[22]

Since the chemical behavior of an element is dictated by its atomic number and all isotopes of the same element have identical behavior, biological systems fail to recognize the difference between atomic weights and treat all isotopes in the same fashion.[23] Therefore, in calculating the cumulated activities for 47 Sc the biodistribution data of 46 Sc were used while considering the physical half-time of 47 Sc.

Before calculating the cumulated activity in source organs, a mass correction method (kg/g method) was used to extrapolate biokinetic data from the animal model to human. In this method, the %ID/g in a certain human organ is equal to the %ID/g in the same mouse organ multiplied by the ratio of the body mass of human and mouse as equation (3).[20] The required mass data for the standard adult male of 73 kg were taken from ICRP89.[24]

Then the activity versus time curves for the source organs including: lung, stomach, intestine, liver, spleen, kidney, bone, muscle, skin, and remainder of the body in human were plotted. The residence times in the source organs are calculated by fitting a multi-component exponential function to these activity-time curves using Matlab software (The Mathworks Inc. R2013.) The program returned the values of fi and λi for the equation (4).

Where fi is the amount of activity associated with the component i of source region, and λi is the biologic elimination constants for the component i=0.693/Ti(hr−1), where Ti is the biological half-time for component i(hr) and λp represents the physical decay constant for the radionuclide of interest.[16],[22] The residence times τ in the source organs were obtained by integration of respective fit functions, from t = 0 to t = infinity, after accounting for the physical decay of the 47 Sc.[25] These values were calculated using the same method as described in the MIRDOSE3 code.[16] Then the cumulated activities in the source organs for a 3.7 MBq (100 μCi) injected activity, in MBq-s, were calculated as equation (2).

One of the parameters for dose calculation is S-factor. The S-factor for each radiation type can be written by equation (5):

In equation (5), D is a measure of the total energy associated with the particular radiation type and is a physical entity known from the radioisotope's decay scheme, f (t, s) is the absorbed fraction for the particular radiation emitted in the source organ, s, and absorbed by the target organ, t, and m is the mass of the target organ.

The absorbed fraction represents the fraction of the total energy emitted by radiation of a particular type that is absorbed in the target organ. For beta particles, which have a short range in tissue, it can be assumed that all the energy will be deposited in the source organ and other target organs will not be irradiated. That is:

Unless t = s, in which case:

So as the S-factor is relevant to the particle energy that is emitted by radionuclide and the particle energies of 46 Sc is different from 47 Sc, for dose calculation the S-factor of 47 Sc is used.

Tables of S for many target and source organs and for many radioisotopes were published in MIRD pamphlet No. 11. In this study, the S-factors for 47 Sc were used from this pamphlet.[26] The S-factor for the remainder of the body, RB, were calculated by equation (8) according to MIRDOSE III computer software recommendation.[16],[25],[27] In equation (5), S(rk ⟵ RB) is the S-factor for remainder of body irradiating target region rk, S(rk ⟵ TB) is the S-factor for total body irradiating target region rk, S(rkrh) is the S-factor for source region rh irradiating target region rk, mTB is the mass of the total body, mRB is the mass of the remainder of the body, and mh is the mass of source region rh .

The radiation absorbed dose to red marrow was also estimated according to MIRD recommendation [25],[28] and calculated by equation (9).

The dynamic bladder model and the gastrointestinal tract model were not used.

The equivalent dose calculated as equation (10) where D T, R is the dose delivered by radiation type R averaged over a tissue or organ T, and wR is the radiation weighting factor for radiation type R. The current values recommended by the ICRP60 in which for photons and electrons, numerical values of the absorbed dose in gray and equivalent dose in sievert are equal. Then effective dose calculated as the product of the individual tissue equivalent doses (HT) and the tissue-weighting factors (wT) according to ICRP 103 and equation (11).[20],[25]

   Results and Discussion Top

Production of 46Sc

Irradiation of natural Sc2O3 target at a thermal neutron flux of for a period of 48h and 8 days after the end of bombardment yielded 46 Sc with a specific activity of ~116.58 MBq/mg (~3.15 mCi/mg). Scandium is mono-isotopic with the atomic mass of 45 and usually, besides 46 Sc, formation of any other scandium radionuclide such as 47 Sc is not expected. However,45 Ca may be formed via the (n, p) reaction.45 Ca is a pure beta emitter and thus difficult to detect. On the other hand considering the cross-sections of (n, γ) and (n, p) reactions on 45 Sc as well as the half-lives of 46 Sc and 45 Ca, it is estimated that the 45 Ca impurity, if at all, was <0.1%.[9] Therefore the radionuclide purity of 46 Sc produced was >98%. The radiochemical purity of 46 Sc was evaluated employing ITLC using two solvent system: (a) In %10 ammonium acetate:methanol (1:1), free Sc 3+ cation was remained at the point of spotting, (b) in 10 mM/L DTPA, free Sc 3+ cation was complexed into more Sc-DTPA form and moved from solvent front while almost no radioactive fraction was remained at the point of spotting. In both chromatographic systems no other radiochemical species was detected [[Figure 2] and [Figure 3]].
Figure 2: 46ScCl3 paper radiochromatogram eluted with 10% ammonium acetate:methanol (1:1)

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Figure 3: 46ScCl3 paper radiochromatogram eluted with diethylenetriaminepenta-acetic acid 10 mM/L

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Preparation and characterization of 46 Sc-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetramethylene phosphonic acid

Radiochemical purity of 46 Sc-DOTMP complex was ascertained by using ITLC. For ITLC %10 ammonium acetate:methanol (1:1) used as the eluting solvent, and it was observed that 46 Sc-DOTMP moved toward the solvent front while 46 ScCl3 under identical conditions remained at the point of spotting.46 Sc-DOTMP complex was obtained with a radiochemical purity of ~93% using 80 mg of DOTMP and 0.35 mg of 46 Sc in 3 ml reaction volume (corresponding to a ligand-to-metal ratio of 60:1) within a pH range of 7–8 at room temperature.

Experiments carried out by keeping the amount of 46 Sc fixed at 0.35 mg and gradually increasing the amount of DOTMP. The excellent complexation yields (~93%) were achieved at ligand to metal ratio of 60:1. [Table 1] shows the complexation yields of 46 Sc-DOTMP obtained at various ligands to metal ratios.
Table 1: Complexation yields of 46Sc-DOTMP complex at different ligand: Metal ratios

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In vitro stability studies

46 Sc-DOTMP complex exhibited excellent in vitro stability at pH ~8 when stored at room temperature. The radiochemical purity of above-mentioned conditions was found to be retained to extend of ~93% after 48 h postpreparation [[Figure 4] and [Figure 5]].
Figure 4: Paper radiochromatogram of "46 Sc-DOTMP" complex eluted with 10% ammonium acetate: methanol (1:1)

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Figure 5: Stability of the 46 Sc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid complex up to 48 h (pH 7–8)

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Biodistribution studies in mice

The uptake of 46 Sc-DOTMP complex in the different organs/tissue of mice expressed as percentage of injected activities (%ID) per organ/tissue at different postinjection times is shown in [Table 2] and [Figure 6]. The results of the biodistribution studies revealed significant bone uptake within 4 h postinjection. The observed uptake in femur at this time point was 3.7 %ID/g corresponding to a skeletal uptake of 33.11 %ID/g for 46 Sc-DOTMP that is similar to the 3.94 %ID/g and 3.72 %ID/g measured by Banerjee et al.[1] for 153 Sm-DOTMP and 153 Sm-EDTMP respectively and reasonably close to the 4.37 %ID/g by Banerjee et al. for 175 Yb-EDTMP. The measured uptake for bone in this study is also close to the 4.23 %ID/g measured by Das et al.[5] for 177 Lu-DOTMP. A comparison between biodistribution results (%ID) in this study for 46/47 Sc-DOTMP, 4 h postinjection and in Neves et al.[11] for 46/47 Sc-IDZBP and 46/47 Sc-Me-IDZBP, 3 h postinjection showed that the former provided significantly better biodistribution profile in animal model because of higher uptake in bone and lower uptake in other major organs [Figure 7].
Figure 6: Percentage of injected dose per gram of 46 Sc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid in mice tissues at 4, 24, 48, 96 and 192 h postinjection

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Figure 7: Comparison between biodistribution results (percentage of injected activities) in this study for 46/47 Sc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid and in Neves et al. for 46/47 Sc-IDZBP and 46/47 Sc-Me-IDZBP

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Table 2: Biodistribution pattern of 46Sc-DOTMP complex in mice

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The estimated %ID for human using a mass correction method are shown in [Figure 8]. The results showed the most of activity was accumulated in the bone, blood and muscle. The activity versus time curves for the source organs were plotted [Figure 9]. The residence times in the source organs are calculated by nonlinear regression analysis that was performed by the activity-time curves [Table 3]. Then cumulated activities in the source organs for a 3.7 MBq injected dose, in MBq-s, were calculated.
Figure 8: Extrapolation of percentage of injected activity of 46 Sc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid in mice to human

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Figure 9: Estimated time-activity curves for organs of human as percentage of injected dose per gram

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Table 3: The residence times in the source organs

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[Table 4] gives the human target organ doses that are estimated by applying MIRD scheme. The human dose estimates indicate that the bone would receive a radiation absorbed dose from 47 Sc-DOTMP is more than 2 times that any other target organ. This estimate was 3.27 mSv/MBq that is >0.920 mSv/MBq measured by Breitz et al.[29] for 166 Ho-DOTMP in patients with multiple myeloma and is almost close to the 3.93 mSv/MBq measured by Simón et al.[30] for 153 Sm-DOTMP. Because of similar nuclear physical characteristic between 153 Sm and 47 Sc, it was assumed that the absorbed dose should have been more closer than these values, but the difference between 153 Sm and 47 Sc could be the result of following factors: 1:different S-values, 2:different formalism for calculating the red marrow accumulated activity that Stabin and et al. indicated [28] and, 3:different experimental conditions. The dose to the red marrow estimated here, 0.836 mSv/MBq, is almost close to the 0.517 mSv/MBq measured by Breitz et al. and near to the 0.755 mSv/MBq measured by Simón et al. The results that obtained in this study are compared with the Breitz et al.'s and Simón et al.'s results in [Figure 10].
Figure 10: Comparison of data that obtained in this study with the Breitz et al.'s and Simón et al.'s results for 153 Sm-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) and 166 Ho-DOTMP

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Table 4: The human absorbed dose estimation

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   Conclusion Top

46 Sc-DOTMP complex was prepared in high yield and excellent radiochemical purity (~93%) using 46 Sc produced by thermal neutron irradiation of natural Sc2O3 target and DOTMP. The complex exhibited excellent in vitro stability (~90% radiochemical purity) at room temperature up to 48 h postpreparation. Radiochemical studies showed that the complex could be prepared in high yield at a ligand-to-metal ratio of 60:1. Biodistribution studies in mice showed rapid selective skeletal uptake of injected activity (3.7 %ID/g in femur at 4 h postinjection) with fast clearance from blood and small uptake in any of the major organs/tissue [Table 2].

Although the principles of inter-species dose extrapolation are poorly understood and applied [31] earlier studies have shown the usefulness of using animal biodistribution as a model for absorbed dose estimations in humans.[32],[33] Therefore, the amount of radiation absorbed doses to human were estimated using MIRD scheme by multiplying the cumulated activities in the source organs that were calculated by estimating %ID for human (using a mass correction method from mice biodistribution data) and using Matlab software, to S-values of 47 Sc from MIRD pamphlet No. 11 and are shown in [Table 4]. The highest absorbed doses were estimated for the bone (3.27 mSv/MBq), red marrow (0.836 mSv/MBq) and large intestine (0.273 mSv/MBq). The absorbed dose for the bone that was estimated in this study is similar to the Simón et al.'s result for 153 Sm-DOTMP [30] [Figure 10]. This result was expected due to almost identical range of beta rays in bone (0.32 mm for 153 Sm and 0.20 mm for 47 Sc [11]). The preclinical results reported here indicated that 47 Sc-DOTMP showed promising features in animal models that warrant further investigation in higher animals to become useful in treating patients with skeletal metastasis.

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Conflicts of interest

There are no conflicts of interest.

   References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]

  [Table 1], [Table 2], [Table 3], [Table 4]


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