جستجوی مقالات مرتبط با کلیدواژه "biodistribution" در نشریات گروه "پزشکی"

Amiloride is a pyrazine compound that inhibits the reabsorption of sodium by blocking sodium channels in the cells of the renal cortex. It has demonstrated promising efficacy in the treatment of cancer in recent times. This study assessed the in vivo biodistribution of amiloride conjugated to dendrimer as a targeted agent utilizing SPECT imaging.

The dendrimer was synthesised using polyethylene glycol and citric acid as precursors, and dicyclohexyl carbodiimide as a zero-order crosslinker. Amiloride was then conjugated to the dendrimer through the terminal amine group, forming an amide bond with the acidic group of the dendrimer. The synthetic particles were assessed by characterization techniques including FTIR, TEM, LC-Mass, and MAP. The response surface optimization method based on the core chemical was employed to achieve maximum labelling efficiency.  The ideal circumstances and biodistribution in the in vivo environment were assessed. 

TThe characterization findings demonstrated the effective formation and linkage of the nanoconjugate. The Radiochemical purity (RCP) of the dendrimer-amiloride complexes with Technetium-99m, achieved under ideal conditions (28 minutes of incubation, 1.4 units of reduced agent, and 17.5 mg of dendrimer-amiloride), exceeds 90%. This demonstrates the considerable potential of dendrimer-amiloride in forming complexes with Technetium-99m. The results from imaging and biodistribution tests showed that 99mTc-dendrimer–amiloride had a high level of activity (7.8 %ID/g) at the tumor site. This was due to the increased expression of sodium channel. 

The favorable characteristics and conduct of the produced nanoprobe indicate its potential as an innovative tool for the advancement of radiopharmaceutical-based medication. Furthermore, it has the capacity to envision a broad spectrum of malignancies.

 The early diagnosis of melanoma is crucial for treatment and management of this aggressive malignancy.   The present study describes the preparation and preclinical evaluation of 68Ga-radiolabeled DOTA-4amino-(I-carboxymethyl) piperidine (Pip)-Nle-cysMSHhex peptide ([68Ga]Ga-CCZ01048) as a potential aide for PET imaging and early diagnosis of malignant melanoma.

 Various parameters were assessed to optimize the final preparation processes. The radiochemical purity of the final complex was checked using RTLC and HPLC methods. The stability of the radiolabeled complex was studied at 15, 30, 60 and 120-min post-injection. The partition coefficient was also studied. Cellular studies of the labeled peptide were measured using B16F10 cells at different post-treatment intervals. The biodistribution of the labeled compound was evaluated using normal and tumor-bearing mice.

 [68Ga] Ga-(Pip)-Nle-cysMSHhex radiolabeled complex was prepared with a specific activity of 118.4 TBq/mmol and radiochemical purity > 99% at optimized conditions. The results of stability studies show that the radiolabeled compound is stable in PBS buffer and human serum after 120 min. The cellular studies demonstrated that a binding affinity of [68Ga] Ga-(Pip)-Nle-cysMSHhex on B16F10 cells and the internalization of the complex increased from about 31% in 30 min to 62% in 240 min post-treatment. The biodistribution studies showed excretion of major portion of the tracer through the kidneys. The remainder of the tracer mostly accumulated at the tumor site. No significant uptake in non-target organs was observed at any interval following injection.

 The [68Ga] Ga-(Pip)-Nle-cysMSHhex radiolabeled complex has the potential as a PET imaging agent for evaluation of metastatic malignant melanoma.

Calculating the organs' radiation dosage in cardiac nuclear medicine procedures is essential in order to identify critical organs, radiation risk assessment and optimization dose value in the injection of radiopharmaceutical drugs. In this study, the biological distribution of 99mTc-2-Methoxyisobutylisonitrile) 99mTc-MIBI as the most common radiopharmaceutical in a cardiac study in human organs based on animal samples was investigated.

After 99mTc-MIBI preparation, radiopharmaceutical was injected into 15 rats. After sacrificing rats, the uptake of radiopharmaceuticals in critical organs at 15, 30, and 45 minutes was measured using an High Purity Germanium (HPGE) detector and the percentage of injected dose per gram of organs was calculated. The cumulative activity was calculated from the radiopharmaceutical transformation diagram with time. The absorption of a radioactive complex in human organs based on animal data was calculated by applying a correction factor. The organs dose was calculated using S factor and the effective dose was calculated using tissue weighting factors.

The mean effective dose per unit of activity was 0.0062 mSv/MBq. The mean effective dose of 27.5 mCi radiopharmaceutical injection was 6.3 mSv. In this study, the absorbed dose in blood, heart, lung, thyroid, liver, spleen, stomach wall, muscle, and bone was calculated as 0.28, 2.92, 1.85, 24.82, 11.13, 7.03, 20.95, 1.11, 4.97, and 22.22 mGy, respectively.

The effective dose of human organs based on the animal model in the study of cardiac nuclear medicine was evaluated by injection of 99mTc-MIBI radiopharmaceutical. The kidneys, salivary glands, thyroid, and spleen were the most critical organs that should be considered in dose optimization studies. The effective dose limit was 28% lower than the values reported in international references.

Brain cancer treatments have mainly failed due to their inability to cross the blood-brain barrier. Several studies have confirmed the presence of glutathione (GSH) receptors on BBB’s surface, as a result, products like 2B3-101, which contain over 5% pre-inserted GSH PEGylated liposomal Doxorubicin, are being tested in clinical trials. Here we conducted the PEGylated nanoliposomal Doxorubicin particles that are covalently attached to the glutathione using the post-insertion technique. Compared with the pre-insertion approach, the post-insertion method is notably simpler, faster, and more cost-effective, making it ideal for large-scale pharmaceutical manufacturing. 

The ligands of the DSPE PEG(2000) Maleimide-GSH were introduced in the amounts of 25, 50, 100, 200, and 400 on the available Caelyx. Following physicochemical evaluations, animal experiments such as biodistribution, fluorescence microscopy, and pharmacokinetics were done. 

In comparison with Caelyx, the 200L and 400L treatment arms were the most promising formulations. We showed that nanocarriers containing 40 times fewer GSH micelles than 2B3-101 significantly increased blood-brain barrier penetrance. Due to the expressed GSH receptors on tissues as an endogenous antioxidant, Doxorubicin will likely concentrate in the liver, spleen, heart, and lung in comparison with Caelyx, according to other tissue analyses. 

The post-insertion technique was found a successful approach with more pharmaceutical aspects for large-scale production. Moreover, further investigations are highly recommended to determine the efficacy of 5% post-inserted GSH targeted nanoliposomes versus 2B3-101 as a similar formulation with a different preparation method.

The use of more potent medicine for local chemotherapy of retinoblastoma in order to minimize local and systemic adverse effects is essential. The main goal of this investigation was to assess the biodistribution of thiolated and methylated chitosancarboxymethyl dextran nanoparticles (CMD-TCs-NPs and CMD-TMC-NPs) following intravitreal (IVT) injection into rat eyes with retinoblastoma.

An ionic gelation method was used to fabricate Cy5-labelled CMD-TCs-NPs and CMD-TMC-NPs. The NPs were characterized. Cellular internalization of Cy5-labelled NPs was investigated using confocal microscopy and the absorption of labeled NPs was quantified by flow cytometry in human retinoblastoma (Y79) cells. In addition, the Cy5-labeled distribution of nanoparticles in the posterior segment of the eye was histologically imaged by confocal microscopy after IVT injection of NPs into the eyes of rats with retinoblastoma.

CMD-TCs-NPs and CMD-TMC-NPs showed a mean diameter of 34 ± 3.78 nm and 42 ± 4.23 nm and zeta potential of +11 ± 2.27 mV and +29 ± 4.31mV, respectively. The in vivo study of intraocular biodistribution of Cy5-labeled CMD-TCs-NPs and CMD-TMCNPs revealed that there is more affinity of CMD-TCs-NPs to the retina and retinoblastoma tumor after IVT administration while methylated chitosan nanoparticles are immobilized in the vitreous and are not able to reach the retina even after 24 hr.

The ionic gelation technique was efficient in synthesizing a biocompatible polymeric nanosystem for drug delivery into the posterior segment of the eye. The current study demonstrated increased ocular bioavailability of CMD-TCs-NPs relative to CMD-TMC-NPs in retinoblastoma induced rat eyes.

Ursolic acid (UA) exhibits anti-hepatocarcinoma and hepatoprotective activities, thus promising as an effective oral cancer therapy. However, its poor solubility and permeability lead to low oral bioavailability. In this study, we evaluated the effect of different ratios of Span® 60-cholesterol-UA and also chitosan addition on physical characteristics and stability of niosomes to improve oral biodistribution.

UA niosomes (Nio-UA) were composed of Span® 60-cholesterol-UA at different molar ratios and prepared by using thin layer hydration method, and then chitosan solution was added into the Nio-UA to prepare Nio-CS-UA.

The results showed that increasing the UA amount increased the particle size of Nio-UA. However, the higher the UA amount added to niosomes, the lower the encapsulation efficiency. The highest physical stability was achieved by preparing niosomes at a molar ratio of 3:2:10 for Span® 60, cholesterol, and UA, respectively, with a zeta-potential value of -41.99 mV. The addition of chitosan increased the particle size from 255 nm to 439 nm, as well as the zeta-potential value which increased from -46 mV to -21 mV. Moreover, Nio-UA-CS had relatively higher drug release in PBS pH 6.8 and 7.4 than Nio-UA. In the in vivo study, the addition of chitosan produced higher intensities of coumarin-6-labeled Nio-UA-CS in the liver than Nio-UA.

It can be concluded that the ratio of Span® 60-cholesterol-UA highly affected niosomes physical properties. Moreover, the addition of chitosan improved the stability and drug release as well as oral biodistribution of Nio-UA.

The main aim of this study is to radiolabel dextran coated iron oxide nanoparticles (NPs) (with 80 nm hydrodynamic size) with the Indium-111 and evaluation their biodistribution after intravenous injection normal mice.

The chelator Diethylenetriamine Pentaacetic Acid (DTPA) dianhydride was conjugated to SPION using a small modification of the well-known cyclic anhydride method at a ratio of 1:5 (NPs:DTPA) molar ratio. The reaction was purified with magnetic assorting columns (MACs) using high gradient magnetic field following incubation. Then the radiochemical purity of the radiolabeled NPs were determined using RTLC method. The magnetic properties of nanoparticles were measured by a 1.5 tesla clinical human MRI.

The NPs showed high super paramagnetic properties whereas their r2/r1 was 17.6. The RTLC showed that the purity of compound was above 99% after purification and the compound has shown a good in-vitro stability until 6 hours in the presence of human serum. The biodistribution of 111In-DTPA-NPs in mice demonstrated high uptake in the reticuloendothelial system (RES) and the blood clearance was so fast.

Due to magnificent uptakes of this radiotracer in the liver and spleen, its stability and their fast clearance from other tissues, especially in blood, it is suggested that this radiotracer would be suitable for RES theranostics purposes.

The efficacy of methotrexate (MTX) as an antimetabolite chemotherapeutic agent highly depends on its blood circulation half-life. In our previous study, different conjugates of MTX (MTX-PEG) were synthesized, their physicochemical properties were investigated and MTX-PEG5000 was finally selected as optimum drug-conjugate for further investigations. In the current work, first the stability of MTX-PEG5000 was studied at 37 °C and the results indicated its high stability in plasma (T1/2 = 144 h) and a relatively rapid degradation in tissue homogenate (T1/2 = 24 h). The study of protein binding pointed out that the conjugate is highly protein-bound (95%). The results of pharmacokinetic studies in mice indicated that MTX-PEG5000 had longer plasma distribution and elimination half-lives compared to free MTX (T1/2 α 9.16 min for MTX-PEG5000 versus 2.45 min for MTX and T1/2 β 88.44 for MTX-PEG5000 versus 24.33 min for MTX). Pharmacokinetic parameters also showed higher area under the curve (AUC) of conjugate compared to parent drug (12.33 mg.mL-1.min for MTX-PEG5000 versus 2.64 mg.mL-1.min for MTX). The biodistribution studies demonstrated that MTX-PEG5000 did not highly accumulate in liver and intestine and had a mild and balanced distribution to other organs. Also, the conjugate was measurable in tissues up to 48 h after injection and was detected in the brain, suggesting the possibility of delivering drug to brain tumors.

In this study Isoniazid (INH) as one of the first line drugs in treatment of Tuberculosis was investigated to be loaded in Solid Lipid Nanoparticles (SLNs) for reducing hepatotoxicity as well as prolonging drug release. High shear homogenization method was performed to prepare INH SLNs. To compare biodistribution of INH before and after loading in SLNs, INH was labeled by Technetium 99 (Tc99) after derivatization. The particle size of the prepared SLNs was 167 and 200 nm before and after lyophilization, respectively. Loading efficiency was calculated using the reverse method and release study was performed by using the dialysis sack method. Loading efficiency was 98%, and more than 85% of the loaded drug released in 3 h. Differential Scanning calorimeter (DSC) studieswere performed for evaluating of the probability of happening hydrogen bonds or other chemical interactions between cholesterol as carrier and isoniazid as active pharmaceutical ingredient. The results could support the probability of hydrogen bond formation between cholesterol and INH. Gamma Scintigraphy studies showed that after administering INH SLNs, longer drug retention in the body was obtained compared to free INH. Quantitative gamma counting showed that the concentration of INH in the liver and intestines could be decreased by using nanotechnology.

The purpose of the present work was to introduce 141Ce-EDTMP as a novel potential future pain palliative agent to patients suffering from disseminated skeletal metastases and diagnostic imaging radioisotope as well. Cerium-141 [T1/2 = 32.501 days, Eβ (max) = 0.580 (29.8%) and 0.435(70.2%) MeV, Eγ = 145.44 (48.2%) keV] possesses radionuclidic properties suitable for use in palliative therapy of bone metastases. 141Ce also has gamma energy of 145.44 keV, which resembles that of 99mTc. Therefore, the energy window is adjustable on the Tc-99m energy because of imaging studies. 141Ce can be produced through a relatively easy route that involves thermal neutron bombardment on natural CeO2 in medium flux research reactors (4–5×1013 neutrons/cm2·s). The requirement for an enriched target does not arise. Ethylenediamine (tetramethylene phosphonic acid) (EDTMP) was synthesized and radiolabeled with 141Ce. The experimental parameters were optimized to achieve maximum yields (>99%). The radiochemical purity of 141Ce-EDTMP was evaluated by radio-thin layer chromatography. The stability of the prepared formulation was monitored for one week at room temperature, and results showed that the preparation was stable during this period (>99%). Biodistribution studies of the complexes carried out in wild-type rats exhibited significant bone uptake with rapid clearance from blood. The images showed high uptake of complex in bone after 72h and 2 weeks clearly. The percentage injected dose per gram of tissue (%ID/g) for each organ or tissue was calculated. The results show significant bone uptake with rapid clearance from blood. The properties of produced 141Ce-EDTMP suggest applying a new efficient bone pain palliative therapeutic agent to overcome metastatic bone pains.

99mTc-Macroaggregated Albumin (99mTc-MAA) has been used as a perfusion agent. This study described development of the 68Ga-MAA via commercially available kits from Pars-Isotopes Company as a 99mTc-MAA kit. 68Ge/68Ga generator was eluted with suprapure HCl (0.6 M, 6 mL) in 0.5 mL fractions. The two fractions with the highest 68GaCl3 activity were generally used for labeling purposes. After labeling, the final product was centrifuged 2 times to purify the solution. Five rats were sacrificed at each exact time interval (from 15 minutes to 2 hours post injection) and the percentage of injected dose per gram (%ID/g) of each organ was measured by direct counting from 11 harvested organs of rats. The RTLC showed that labeling yields before centrifuges were 90% and 95% for Pars-Isotopes and GE kits, respectively and after centrifuges, they became 100%. The microscopic size examination showed a shift in the particle sizes post centrifuges and the biodistribution data revealed the efficiency and benefits of centrifuges in terms of preventing the of liver and bone marrow uptakes especially for Pars-Isotopes kits. Our results showed that after centrifuges of the final product, the lung uptakes increased from 89% to more than 97% of %ID/g after 5 min post injections. The whole procedure took less than 25 min from elution to the final product. Since 99mTc-MAA remained longer than 68Ga-MAA in the lung and 68Ga-MAA showed better image qualities, using 68Ga-MAA is recommended.

The major challenge to treat Parkinson’s disease (PD) is penetration of target molecule into the brain to improve the efficacy of drugs. To achieve better brain penetration and targeted delivery, 1,9-Pyrazoloanthrone (1,9-P) loaded liposomes were developed by solvent injection technique using ultrasonication and evaluated for particle size, morphology, entrapment efficiency, FT-IR, and in-vitro drug release studies. The potential of 1,9-Pyrazoloanthrone (1,9-P), a c-Jun-N-terminal Kinase (JNK-3) inhibitor which could stop or retard the rate of apoptosis of neuronal cells was also evaluated. In-vivo pharmacokinetic and brain uptake studies of liposomes were performed to investigate the bioavailability and brain distribution of 1,9-P. Cytotoxicity and neuroprotection were done on SH-SY5Y cell line using MTT and AO/EB apoptosis assay. The optimized batch of liposomes showed an average size of 112.33 ± 0.84 nm with a zeta potential value of -19.40 mV and 78.96 ± 0.28% drug entrapment efficiency. The in-vitro release studies demonstrated the sustained release profile of liposome up to 24 h. The pharmacokinetic data in Wistar rats over the period of 12 h demonstrated 4.82-folds greater AUC (0-12 h) for liposome in brain compared with 1,9-P suspension. Cytotoxicity assay showed no sign of toxicity, whereas apoptosis assay revealed a neuroprotective action of liposomes. The results demonstrated successful targeting of the 1,9-P, to brain as a novel strategy having significant therapeutic potential to treat PD.

In this work, 153Sm-zoledronate (153Sm-ZLD) was studied using computational chemistry methods and prepared for possible use in bone pain palliation therapy.
The Sm(ZLD)2.7H2O complex was synthesized and characterized in solid state using computational chemistry methods followed by 153Sm-ZLD complex production, stablity, hydroxyapatite (HA) tests and also biodictribution studies in animals were studied and used for absorbed dose determination in critical organs.
The Sm(ZLD)2.7H2O complex was synthesized and characterized in solid state and computational chemistry methods showed that 1:1, 1:2 and 1:3 complex formation are possible in aqueous solution. 153Sm-ZLD complex was prepared with >99% radiochemical purity (ITLC, HPLC) and specific activity of 4.4 GBq/mmol. It was stable for 24h with >95% binding to HA with accumulation in rat bones and kidneys. Absorbed dose showed kidney and osteogenic tissue as critical organs.
The 153Sm-ZLD complex data were compared to 153Sm-EDTMP and 153Sm-BPAMD.

Targeted radionuclide therapy (TRT) has been demonstrated to be an effective therapeutic tool in patients with disseminated bone metastasis. TRT is generally performed with a single radionuclide. In this study we investigated the feasibility of combined TRT with a high-energy beta emitter (153Sm) and a low energy beta emitter (177Lu) in wistar rats.
The cocktail complex of 153Sm/177Lu-EDTMP was prepared. To determine the effect of metal-to-ligand (Me:EDTMP) molar ratio on labeling yield, several complex were analyzed after changing Me:EDTMP molar ratio from 1:1 to 1:50. 153Sm/177Lu-EDTMP was administered intravenously through the tail vein of wistar rats. Biodistribution data were collected at 2 hours to 7 day post injection and scintigraphic images were taken at 24 hours and 1, 2 week after administration of radiopharmaceutical.
The results revealed high skeletal uptake (3.5% and 3.4% ID/g at 24 hours post injection for 153Sm and 177Lu, respectively) with rapid blood clearance and minimal uptake in any of the major organs. Scintigraphic images verified high skeletal uptake.
Our results indicate that the combination of 153Sm and 177Lu is feasible and safe. This study suggests that the combination of different radionuclides with different radiation energies and half-life, such as 153Sm and 177Lu, could be advantageous in patients with tumoral lesions of different sizes.

This study describes the preparation, biodistribution of 153Sm-DTPA-SPION after intravenous injection in rats.
The chelator DTPA dianhydride was conjugated to SPION using a small modification of the well-known cyclic anhydride method. Conjugation was done at a 1: 4 (SPION: ccDTPA) molar ratio. Conjugation reaction was purified with magnetic assorting column (MACs) using high gradient magnetic field following incubation, the radio labeled conjugate was checked using RTLC method for labeling and purity checked.
The RTLC showed that labeling yield was above 99% after purification and the compound have good in vitro stabilities until 48 hr post injection in the presence of human serum. The biodistribution of 153Sm-DTPA-SPION in rats showed dramatic uptake in the reticuloendothelial system (RES) and their clearance is so fast in other organs especially in the blood. Biodistribution results show that after 30 min post injection more than 84% of injected activities were taken up by the liver and spleen (about 64% and 20%, respectively).
Due to magnificent uptakes of this radiotracer in the liver and spleen and their fast clearance from other tissues, especially in blood, it is suggested that this radiotracer would be a potential candidate for RES theranostic purposes.

PR81 is a monoclonal antibody that binds with high affinity to MUC1 that over expressed on breast tumors. PR81 is considered a suitable targeting molecule that was radiolabeled using Cu-64 for positron imaging studies. The monoclonal antibody was conjugated with DOTA moiety and after purification was evaluated for radiochemical purity, immunoreactivity, cell toxicity and structure integrity as well as biodistribution study in normal rats. The radiolabeled antibody prepared with acceptable radiochemical purity (> 93.2 ± 0.6 %, ITLC; specific activity; 4.6 µCi/µg), protein structure integration, significant cytotoxicity and significant immunoreactivity retention was assessed by radioimmunoassay (RIA). Animal biodistribution of the 64Cu-DOTA-PR81 was consistent with other radiolabeled antibodies. The results showed that 64Cu-DOTA-PR81 may be considered for tumor imaging for ultimate diagnosis and follow-up of MUC1 expression in oncology.

Somatostatin receptors expressed on a wide range of human tumors, are potential targets for the peptide receptor radionuclide therapy (PRRT). In this study, 177Lu-[DOTA-DPhe1, Tyr3]octreotide (177Lu-DOTATOC) as an agent for PRRT was prepared and its biodistribution was studied in rats.
The best condition for the preparation of the 177Lu-DOTATOC radiolabeled complex was determined by various experiments. Radiochemical purity of the radiolabeled complex was checked using ITLC method. The stability of the complex in room temperature and in human serum was studied up to 48 h. The biodistribution of 177Lu-DOTATOC solution was investigated in male rats at each selected interval time (2, 4, 24, 48, 72 and 168 h) after injection and compared with the biodistribution of 177LuCl3 solution in the same-type rats.
177Lu-DOTATOC was prepared successfully with radiochemical purity of higher than 99% in 30 min at the optimized conditions. The stability of the radiolabeled complex at room temperature and in human serum at 37 °C showed no decrease in the radiochemical purity even after for 48 h. The biological behavior of the complex showed a major difference uptake with 177LuCl3 solution especially in the liver and spleen and also in somatostatin receptor-positive tissues such as pancreas and adrenal.
The results showed that 177Lu-DOTATOC has the comparable pharmacokinetic with the other DOTATOC complexes, while has completely different pattern compared with 177Lu cation.

In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA conjugated alendronate (DOTA-ALN) was synthesized and evaluated after labeling with gallium-68 (68Ga).
DOTA-ALN was synthesized and characterized, followed by 68Ga-DOTA-ALN preparation, using DOTA-ALN and 68GaCl3 (pH: 4-5) at 92-95°C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation,
biodistribution studies, and imaging were performed on the developed agent in normal rats.
The complex was prepared with high radiochemical purity (>99% as depicted by radio thin-layer chromatography; specific activity: 310-320GBq/mmol) after solid phase purification and was stabilized for up to 90 min with a logP value of -2.91. Maximum ligand binding (65%) was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low ( The high solubility and anionic properties of the complex led to major renal excretion and low hydroxyapatite uptake; therefore, the complex failed to demonstrate bone imaging behaviors.

In this study, production, quality control and biodistribution studies of 166Ho-zoledronate have been presented as a possible bone marrow ablative agent. Ho-166 chloride was produced by thermal neutron irradiation of natural 165Ho(NO3)3 samples. 166Ho-zoledronate complex was prepared by adding the desired amount of zoledronate solution (0.2 mL, 150 mg/ml in 1 M NaOH) to appropriate amount of the 166HoCl3 solution. Radiochemical purity of the complex was monitored by instant thin layer chromatography (ITLC). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. The biodistribution of 166Ho-zoledronate and 166HoCl3 in wild-type mice was checked up to 72 h. 166Ho-zoledronate complex was prepared in high radiochemical purity (> 99%, ITLC) and specific activity of 4.4 GBq/mmol. The major accumulation of radiolabelled complex was observed in the bone tissue. These findings suggest 166Ho-zoledronatehas can be a possible candidate for bone marrow ablation in patients with multiple myeloma.

Compartmental analysis allows the mathematical separation of tissues and organs to determine activity concentration in each point of interest. Biodistribution studies on humans are costly and complicated, whereas such assessments can be easily performed on rodents.
In this study, we aimed to develop a pharmacokinetic model of 153Sm-maltolate complex as a novel therapeutic agent and free 153Sm cation in normal rats using compartmental analysis to evaluate the behavior of this complex.
We developed a physiologically-based pharmacokinetic model for scaling up the activity concentration in each organ with respect to time. In the mathematical model, physiological parameters including organ volume, blood flow rate, and vascular permeability were used. The compartments (organs) were connected anatomically, which allowed the use of scale-up techniques to predict new complex distribution in each body organ.
The concentration of 153Sm-maltolate complex and free 153Sm cation in various organs was measured at different time intervals. The time-dependent behavior of the biodistribution of these two radiotracers was modeled, using compartmental analysis; the detected behaviors were drawn as a function of time.
The variation in radiopharmaceutical concentration in organs of interest could be described by summing seven to nine exponential terms, which approximated the experimental data with a precision of > 1% in comparison with the original data from animal studies.