Optimized preparation and preliminary evaluation of [64Cu]–DOTA–trastuzumab for targeting ErbB2/Neu expression

Breast cancer radioimmunoscintigraphy targeting HER2/neu expression is a growing field of work in nuclear medicine research. Trastuzumab is a monoclonal antibody that binds with high affinity to HER2/neu, which is over expressed on breast and other tumors. Developing new tracers for the detection of this cancer is of great interest. In this study, trastuzumab was successively labeled with [⁶⁴Cu]CuCl₂ after conjugation with DOTA-NHS-ester. The conjugate was purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated and total concentration was determined by spectrophotometric method. DOTA–trastuzumab was labeled with ⁶⁴Cu produced by ⁶⁸Zn(p,αn)⁶⁴Cu nuclear reaction (30 MeV protons at 180 μA). Radiochemical purity, integrity of protein after radiolabeling and immunoreactivity of radiolabeled mAb trastuzumab with HER2/neu antigen and SkBr3 cell line were performed by RIA. In vitro stability of radiolabeled mAb in human serum was determined by thin layer chromatography. In vitro internalization studies were performed with the SkBr3 cell line and the tissue biodistribution of the ⁶⁴Cu–DOTA–trastuzumab was evaluated in wild-type rat (90 ± 5.5 μCi, 2, 6, 12, 24 h p.i.). The radioimmunoconjugate was prepared with a radiochemical purity of higher than 96 ± 0.5 % (ITLC) and specific activity as high as 5.3 μCi/μg. The average number of chelators per antibody for the conjugate used in this study was 5.8/1. The sample was showed to have similar patterns of migration in the gel electrophoresis. The ⁶⁴Cu–DOTA–trastuzumab showed high immunoreactivity towards HER2/neu antigen and SkBr3 cell line. In vitro stability of the labeled product was found to be more than 94 % in PBS and 82 ± 0.5 % in human serum over 48 h. In vitro internalization studies of the ⁶⁴Cu–DOTA–trastuzumab showed that up to 11.5 % of the radioimmunoconjugate internalized after 10 h. The accumulation of the radiolabeled mAb in liver, skin, intestine, lung, spleen, kidney and other tissues demonstrates a similar pattern to the other radiolabeled anti-HER2 immunoconjugates. ⁶⁴Cu–DOTA–trastuzumab is a potential compound for molecular imaging of PET for diagnosis and treatment studies and follow-up of HER2 expression in oncology.     

Biodistribution of ultra small superparamagnetic iron oxide nanoparticles in BALB mice

Recently ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs) have been widely used for medical applications. One of their important applications is using these particles as MRI contrast agent. While various research works have been done about MRI application of USPIOs, there is limited research about their uptakes in various organs. The aim of this study was to evaluate the biodistribution of dextran coated iron oxide NPs labelled with ^99mTc in various organs via intravenous injection in Balb/c mice. The magnetite NPs were dispersed in phosphate buffered saline and SnCl₂ which was used as a reduction reagent. Subsequently, the radioisotope ^99mTc was mixed directly into the reaction solution. The labeling efficiency of USPIOs labeled with ^99mTc, was above 99 %. Sixty mice were sacrificed at 12 different time points (From 1 min to 48 h post injections; five mice at each time). The percentage of injected dose per gram of each organ was measured by direct counting for 19 harvested organs of the mice. The biodistribution of ^99mTc-USPIO in Balb/c mice showed dramatic uptake in reticuloendothelial system. Accordingly, about 75 percent of injected dose was found in spleen and liver at 15 min post injection. More than 24 % of the NPs remain in liver after 48 h post-injection and their clearance is so fast in other organs. The results suggest that USPIOs as characterized in our study can be potentially used as contrast agent in MR Imaging, distributing reticuloendothelial system specially spleen and liver.     

Radioactivity in coffee

This research was dedicated to the study of the background levels of ²¹⁰Po and natural gamma emitters as ⁴⁰K, ²¹⁴Pb, ²¹⁴Bi, ²²⁸Ac, ²¹²Pb and ²¹²Bi in coffee powder and in coffee beverage; also the artificial ¹³⁷Cs was determined. In the coffee powder the mean ²¹⁰Po activity resulted 7.25 ± 2.25 × 10^?2 Bq kg^?1. ⁴⁰K showed a mean activity of 907.4 ± 115.6 Bq kg^?1. The mean activity concentration of ²¹⁴Pb and ²¹⁴Bi, indicators of ²²⁶Ra, given as mean value of the two radionuclides, resulted 10.61 ± 4.02 Bq kg^?1. ²²⁸Ac, ²²⁸Ra indicator, showed a mean activity concentration of 13.73 ± 3.20 Bq kg^?1. The mean activity concentration of ²¹²Pb, ²²⁴Ra indicator, was 8.28 ± 2.88 Bq kg^?1. ²⁰⁸Tl, ²²⁴Ra indicator, presented a mean activity concentration of 11.03 ± 4.34 Bq kg^?1. In all samples, the artifical ¹³⁷Cs resulted below the detection limit (2.0 Bq kg^?1). The arithmetical mean value of percentage of ²¹⁰Po extraction in coffee beverage resulted 20.5 ± 6.9. The percentage of transfer of gamma emitters,⁴⁰K, ²¹⁴Pb, ²¹⁴Bi, ²²⁸Ac, ²¹²Pb, ²⁰⁸Tl resulted of 80.0, 33.5, 24.7, 30.0, 35.1 and 53.5 % for ⁴⁰K, ²¹⁴Pb, ²¹⁴Bi, ²²⁸Ac, ²¹²Pb and ²⁰⁸Tl respectively.     

Search of ligands suitable for 212Pb/212Bi in vivo generators

The short half-life of ²¹²Bi and ²¹³Bi limits the application of these radionuclides in α radionuclide therapy. The labeling of biomolecules with ²¹²Pb (mother nuclide of ²¹²Bi) instead of ²¹²Bi or ²¹³Bi has the advantage of obtaining a conjugate with a half-life of 10.6 h, compared with of 60 min for ²¹²Bi or 46 min for ²¹³Bi. Previous attempts to prepare a potential in vivo generator with ²¹²Pb complexed by the DOTA chelator failed, because about 36 % of Bi was reported to escape as a result of the radioactive decay $^{{212}}{\text{Pb}}{\mathop{\longrightarrow}\limits^{\beta ^{ - }}}{^{212}{\text{Bi}}}$ . Herein, we report studies on the stability of the ²¹²Pb complexes with eight selected polydentate ligands, which demonstrate high affinity for 3+ metal cations. From the ligand studied DOTP and BAPTA show a sufficient ²¹²Pb labeling yields but only ²¹²Pb–DOTP complex is stable in isotonic solution of sodium chloride making this way radioactivity level of released ²¹²Bi is below the limit of detection. It should be emphasized that the DOTP complex is stable only in the case when the concentration of free DOTP exceeds 10^?4 M.     

Radionuclides and trace elements in centipede species Scolopendra cingulata from Serbia

The adults of centipede Scolopendra cingulata from Serbia have been analyzed for ²¹⁴Bi, ¹³⁷Cs, ²²⁸Ac, ⁴⁰K, ²¹²Pb and ²¹⁴Pb activity. The top 5 cm of soil from the same locations (Novi Pazar, Izbice and P?inja) is also measured—to estimate upper limit of the soil–S. cingulata radionuclide transfer factors (i.e., S. cingulata/soil concentration ratios), as well as the total dose rate—external and internal exposure. Cesium-137 activity was found to be below (or equal to) minimum detectable activity in all 16 specimens. The highest measured ²¹⁴Bi activity was 0.1 Bq g^?1, while ²²⁸Ac—0.086 Bq g^?1, ⁴⁰K—0.12 Bq g^?1, ²¹²Pb—0.012 Bq g^?1 and ²¹⁴Pb—0.029 Bq g^?1. Bismut-214 transfer factors are found to range from <0.34 to 6, as ²²⁸Ac—from <0.4 to 3, whilst the total dose rate is found to be less than 18 μGy h^?1. The As, Se, Cd, Co, Cr, Cu, Mn, Ni, Pb, but also Zn and Fe concentrations—in three individuals, were also determined. All the elements showed concentrations in the P?inja S. cingulata significantly lower than in S. cingulata from Novi Pazar and Izbice.     

Preparation of 186Re-MIBI complex for myocardial perfusion imaging as potential replacement of analogues 99mTc-MIBI complex

The optimum conditions to label 2-methoxyisobutyl-isonitrile (MIBI) compound with pure ¹⁸⁶Re as a stable contrast agent for myocardial perfusion imaging were investigated. Complexation of MIBI with ¹⁸⁶Re was carried out using anhydrous stannous chloride, gentisic acid and 1 ml of 37 MBq ¹⁸⁶ReO₄ ^? at pH 2 in a boiling water bath for 30 min. The corresponding radiochemical yield was ≈95.5 %. The biodistribution studies in mice indicated that, the complex was cleared from the body by kidneys to urinary bladder and finally into urine. ¹⁸⁶Re-MIBI demonstrated satisfactory heart uptake like to ^99mTc- MIBI (8.94 % dose/organ at 5 min). The obtained data showed that ¹⁸⁶Re-MIBI is a potential replacement of ^99mTc-MIBI for myocardial perfusion imaging.     

Neutron dose estimation for 1H+9Be and 1H+12C reactions at 20 MeV proton energy via LET spectrometry using CR-39 detectors

The neutron dose is estimated by linear energy transfer (LET) spectrometry method for two reactions, viz. ¹H+⁹Be and ¹H+¹²C at 20 MeV proton energy using CR-39 track detectors. The LET spectrum is generated from the major, minor radii of each track and thickness of removed surface from each side of the detector due to chemical etching. Microdosimetric distributions of absorbed dose and dose equivalents are obtained from the LET spectrum. The absorbed dose and dose equivalent per incident proton obtained from the LET spectra are found to be about 12.5 and 8 times higher in ¹H+⁹Be reaction than ¹H+¹²C reaction.     

Pre-concentration of short-lived radionuclides using manganese dioxide precipitation from surface waters

Rapid determination of ²²²Rn and ²²⁰Rn progeny (²¹⁴Pb, ²¹²Pb, ²¹⁴Bi, ²¹²Bi) is achievable using manganese dioxide (MnO₂) precipitation with analysis by γ-spectrometry. This is of interest to environmental monitoring programmes that utilise gross activity methods to screen for anthropogenic radionuclides. The contribution from these naturally occurring radionuclides (NOR) varies, and is difficult to experimentally measure due to short half-lives (t _½ = 19.9 m–10.64 h) and low environmental activity (<0.1 Bq L^?1). The extraction efficiency of the technique is above 90%, and above 80% for other nuclides (²³²Th, ²³⁸U, ²³⁵U, ²²⁸Ac, ²²⁶Ra, ²²⁴Ra, ²¹⁰Pb, ⁵⁴Mn). Short-lived NOR have been measured at two surface water locations, and indicates elevated ²¹⁴Bi activity of 4.0 ± 1.1 Bq L^?1.     

Radiolabeling of EGCG with 125I and its biodistribution in mice

The aim of the present study was to label EGCG with ¹²⁵I and to determine its radiopharmaceutical potential in mice. EGCG was labeled with ¹²⁵I using the iodogen method. The labeling yield and the radiochemical purity of ¹²⁵I–EGCG were determined by radio thin-layer chromatography (RTLC). The Labeling yield was approximately 89.4 %. The radiochemical purity was approximately 96.4 %. The biodistribution studies of the labeled compound (specific activity; 0.47 TBq/μg) were performed in male Kunming mice. The uptakes of ¹²⁵I–EGCG in some organs were determined at different time after injection to the mice. The radioactivity in each organ was counted and the percentage of injected activity per gram of tissue weight (%ID/g) for each organ and blood was calculated. Incorporation of radioactivity in the various tissue/organ was confirmed by microautoradiography. ¹²⁵I–EGCG uptake in the stomach and salivary gland was higher than other organ/tissue. The black silver grains was concentrated in the nucleus, cytoplasm, intercellular substance and capillaries of that various organs, and its unevenly distributed. Thus, ¹²⁵I–EGCG may be radiopharmaceutical for the imaging of the stomach and salivary gland.     

Development of a method for high LET irradiation of liquid systems

A variety of processes, from material sterilization and cancer treatment to used nuclear fuel recycling, benefit from quantifying the sensitivity of the system to radiation. Determining the effects of alpha irradiation on a system may be of complementary interest to the effects of gamma irradiation, as alpha radiation has higher linear energy transfer (LET) and will likely result in different chemical damage effects. This becomes important in advanced nuclear fuel cycle processes where the radioactive materials to be handled in solutions contain significant amounts of alpha emitters. Here we describe a method for studying high LET radiation in a liquid system using a TRIGA^® reactor and the ¹⁰B(n,α)⁷Li reaction. By fitting a model based on neutron diffusion and absorption to experimentally obtained Fricke dosimetry data, the high LET dose to a sample was predictable over the full range of reactor power available and varying ¹⁰B concentration. This method may be applied to study the effects of high LET radiation on any liquid system as long as a suitable molecule containing boron is used and appropriate neutron diffusion coefficients are known. A wide range of high LET dose rates from <10 Gy/h to >1,000 kGy/h may be obtained with this method.     

Effects of pH, concentration and temperature on radionuclides sorption onto polyhydroxyethyl methacrylate-expanded perlite composite

Poly (hydroxyethylmethacrylate-expanded perlite) [P(HEMA-EP)], was synthesized and its adsorptive features were investigated for natural radionuclides (TI⁺, Ra²⁺, Bi³⁺, Ac³⁺ and Pb²⁺) in aqueous media at differing initial pH, initial radionuclides concentration and adsorption thermodynamics. The amounts of natural radionuclides at equilibrium were determined by gamma spectrometry. The Langmuir adsorption capacities (X_L) were found to be in the order of ²¹²Pb (0.4 MBq kg^?1) > ²²⁸Ac and ²⁰⁸Tl (0.3 MBq kg^?1) > ²²⁶Ra and ²¹²Bi (0.2 MBq kg^?1). These findings indicated that P(HEMA-EP) adsorbed natural radionuclides with high affinity. It was also demonstrated that the adsorption mechanism was spontaneous (ΔG < 0), the process was exothermic (ΔH < 0) thus increasing entropy (ΔS > 0). The composite was reused for four more times after regeneration without any detectable changes either in its structure or adsorptive capability.     

Trastuzumab quantification in serum: a new,rapid, robust ELISA assay based on a mimetic peptide that specifically recognizes trastuzumab

Trastuzumab, a humanized monoclonal antibody directed against the epidermal growth factor receptor 2 (HER2), is a milestone in the treatment of HER2-overexpressing breast cancer patients. An enzyme-linked immunosorbent assay (ELISA) for trastuzumab has been developed for routine use in the laboratory to support clinical and pharmacokinetic studies to optimize therapy. The method relies on an antigen peptide linked to a 96-well plate via the streptavidin/biotin system. The peptide sequence mimics the extracellular portion of the HER2 receptor that is recognized by trastuzumab. The calibration range of the assay is 10 to 360 ng/mL per well, corresponding to a trastuzumab serum concentration from 5 to 180 μg/mL with a lower limit of quantification of 10 μg/mL. Validation results demonstrate that trastuzumab can be accurately and precisely quantified in human serum using this assay. The procedure was also tested in sera obtained from breast cancer patients to evaluate trastuzumab serum levels, confirming the applicability of method that could be a valid assay to use in daily laboratory practice.     

Production, quality control and pharmacokinetic studies of 177Lu–zoledronate for bone pain palliation therapy

A new dipeptide derivative, ethyl 2-(3-(4-hydroxyphenyl)-2-(2-(4-phenyl-5-((pyridin-4-ylamino)methyl)-4H-1,2,4-triazol-3-ylthio)acetamido)propanamido)-3-(1H-indol-3-yl)propanoate (EHPTIP) was successfully synthesized and radiolabeled with ¹²⁵I by the direct electrophilic substitution method. The non radiolabeled compound (EHPTIP) was tested as an antimicrobial agent and the radiolabeled derivative was tested as a new imaging agent. The study results showed a good antimicrobial activity of EHPTIP and a good in vitro and in vivo stability of ¹²⁵I-EHPTIP. The biodistribution of the radiolabeled compound showed a high brain uptake of 7.60 ± 0.01 injected activity/g tissue organ at 30 min post-injection and retention in brain remained high up to 1 h, whereas the clearance from the normal mice appeared to proceed via the renal system. Such brain uptake is better than that of currently used radiopharmaceuticals for brain imaging (^99mTc-ECD and ^99mTc-HMPAO). As a conclusion, EHPTIP is a newly synthesized dipeptide with a good antimicrobial activity and the radioiodinated EHPTIP which is labeled with ¹²³I could be used as a novel agent for brain SPECT.     

Preparation and biological evaluation of radiogallium labeled glucagon for SPECT imaging

In this work, recently prepared ⁶⁷Ga-labeled glucagon (⁶⁷Ga-DTPA-GCG) for imaging studies (radiochemical purity >94%; HPLC, S.A. 296–370 GBq/mM) was used in biological studies. The wild-type rat biodistribution results, 2 h post injection, demonstrated high tissue:muscle ratios for target tissues (liver, kidney, heart, spleen, fat intestine stomach and pancreas), 234, 18.45, 7.12, 1.75, 128.7, 4.9, 6.3 and 1.11, respectively. The tracer binding capacity using freshly prepared rat brain homogenate demonstrated significant specific binding of the tracer to neuronal GCG receptors (⁶⁷Ga-DTPA-GCG/⁶⁷Ga:3 and ⁶⁷Ga-DTPA-GCG/⁶⁷GaDTPA:2.2 at 90 min). SPECT images also demonstrated target specific binding of the tracer at 4 h. The data suggests the tracer is accumulated in GCGR rich tissues 2–4 h post injection, suggesting potentials of the tracer for future imaging studies in glocagonoma models.     

Studies of high linear energy transfer dosimetry by 10B(n,α)7Li reactions in aqueous and organic solvents

Advanced chemical treatment processes such as aqueous separation techniques can be used to separate the reusable materials from used nuclear fuel, reducing the radiotoxicity and storage time of the remaining waste. The degradation of chemicals in these processes has been studied utilizing gamma radiation. However, radiolytic degradation by internal alpha emitters has not been as widely investigated due to the difficulty of finding appropriate internal sources. This work presents results using a method to produce alpha particles in situ in aqueous and organic solvents representative of liquid–liquid extraction systems. The method is based on the widely studied ¹⁰B(n,α)⁷Li reaction which has previously been studied in aqueous solutions. Neutrons were supplied from the UCI TRIGA^® nuclear reactor. Comparisons were also made to gamma radiation from a ¹³⁷Cs source. We report that the method is useful for inducing high linear energy transfer (LET) doses in aqueous and organic solutions. We used the classic iron sulfate-based Fricke dosimeter for dosimetry in aqueous solutions and methyl red (2-[(4-dimethylaminophenyl)diazenyl]benzoic acid) dissolved in n-dodecane for organic solvents. High LET doses in both aqueous and organic solvents are well described and a simple linear relationship was found based on the neutron flux and total boron concentration. We have established, using spectroscopic determination, that methyl red degrades in a linear fashion with absorbed dose up to 80 kGy and G-values for the methyl red degradation in n-dodecane were found to be 4.66 × 10^?4 μmol/J for external ¹³⁷Cs gamma radiation and 3.0 × 10^?5 μmol/J for ¹⁰B(n,α)⁷Li induced high LET radiation.     

Synthesis and Feasibility Evaluation of a new Trastuzumab Conjugate Integrated with Paclitaxel and 89Zr for Theranostic Application Against HER2-Expressing Breast Cancers

The preparation and in vitro evaluation of a theranostic conjugate composed of trastuzumab, paclitaxel (PTX), and deferoxamine (DFO)-chelated ⁸⁹Zr have been reported. These comounds have potential applications against HER2 receptor positive breast cancers. We conjugated DFO and PTX to trastuzumab by exploiting simple conjugation chemistry. The conjugate (DFO-trastuzumab-PTX) showed excellent radiolabeling efficiency with ⁸⁹Zr and the labeled conjugate had high in vitro stability in human serum. Furthermore, DFO-trastuzumab-PTX displayed comparable cytotoxicity with PTX and ⁸⁹Zr-DFO-trastuzumab-PTX exhibited HER2 receptor-mediated binding on HER2-positive MDA-MB-231 breast cancer cells. The results of our in vitro study indicate high potential of ⁸⁹Zr-DFO-trastuzumab-PTX to be utilized in the theranostic application against HER2-postive breast cancers.     

Synthesis and evaluation of a series of 99mTc-labelled zoledronic acid derivatives as potential bone seeking agents

Developing novel superior bone-seeking radiopharmaceuticals for the detection of malignant bone lesions could further improve the diagnostic value of routine bone scanning. A series of radiolabeled diphosphonates (^99mTc-EIPrDP, ^99mTc-EIBDP and ^99mTc-EIPeDP) have been designed and synthesized successfully in high chemical yields and radiochemical purity. The in vitro and in vivo biological properties were systematically investigated and compared. The biodistribution in mice shows that ^99mTc-EIPrDP has higher bone uptake (13.3 ± 1.23) than those of ^99mTc-EIBDP and ^99mTc-EIPeDP (11.7 ± 0.28 and 8.69 ± 0.04 %ID/g) at 1–2 h post injection. It also has the highest uptake ratio of bone to muscle, spleen and heart, respectively, and faster blood clearance in early times. The present study indicates that ^99mTc-EIPrDP holds great promise as a bone imaging agent.     

Synthesis and evaluation of a phenylbenzothiazole-based 99mTc(CO)3-radiotracer for possible application in imaging of β-amyloid plaques in Alzheimer’s disease

The 2-phenyl benzothiazole pharmacophore is known to have high affinity for amyloid beta (Aβ) and is therefore derivatized, to [N-(4′-benzothiazol-pyridin-2-yl-methyl-amino)-acetic acid (BTPAA)] for radiolabeling with [^99mTc(CO)₃(H₂O)₃]⁺ precursor. The radiotracer, ^99mTc(CO)₃–BTPAA is evaluated in vitro and in vivo to determine its binding with the Aβ and ability to cross the blood brain barrier. The radiotracer prepared in >95 % radiochemical yield, showed ~25 % inhibition in presence of thioflavin-T, indicating its specificity towards aggregated Aβ protein. The radiotracer also showed brain uptake of 0.25 ± 0.04 % injected dose/g at 2 min post injection, indicating its ability to cross the blood brain barrier.     

Sedimentation and lateral transport of 210Pb over the East China Sea Shelf

²¹⁰Pb is an effective tracer of constraining particle transport and sedimentation in shelf regions. To reveal the spatial pattern of ²¹⁰Pb over the East China Sea (i.e. ECS) Shelf, ²¹⁰Pb in the surface sediments were examined at 11 stations, as well as ²³⁴Th and ²¹⁰Pb in the water column at four stations. Overall, the plume zone of the Yangtze River along the coastline is a source area of ²¹⁰Pb for the outer shelf, exporting 0.46 dpm cm^?2 year^?1 at least, which accounts for about 25 % of ²¹⁰Pb input into this region. In the southern ECS Shelf to the north of the Taiwan Strait, the focusing factor (f) values are higher than unity, indicating a sink area of ²¹⁰Pb. Boundary scavenging of ²¹⁰Pb contributes 0.36 dpm cm^?2 year^?1 to this sink area on the basis of a mass balance model evaluation. Lateral transport of ²¹⁰Pb to this region, quantified by ²³⁴Th and ²¹⁰Pb in the water column, varied from 3.34 to 6.39 dpm cm^?2 year^?1 with an average of 4.83 dpm cm^?2 year^?1, also supporting its sink characteristic. To the southwest of the Cheju Island, the f values were less than unity, revealing a source region of ²¹⁰Pb. The average export flux of ²¹⁰Pb from this region was 1.64 dpm cm^?2 year^?1. Therefore, ²¹⁰Pb sedimentation/settling showed significantly heterogeneous sedimentation of particulate matter over the ECS Shelf.     

Development and evaluation of a 166holmium labelled porphyrin complex as a possible therapeutic agent

Porphyrins are interesting derivatives with low toxicity, tumor avidity and rapid wash-out suggested as potential radiopharmaceuticals in radiolabeled form. In this work, [¹⁶⁶Ho] labeled 5,10,15,20-tetrakis(phenyl) porphyrin ([¹⁶⁶Ho]-TPP) was prepared using [¹⁶⁶Ho]HoCl₃ and 5,10,15,20-tetrakis(phenyl)porphyrin (H₂TPP) for 12 h at 50 °C (radiochemical purity: >95 ± 2 % ITLC, >99 ± 0.5 % HPLC, specific activity: 0.9–1.1 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 48 h. The partition coefficient was calculated for the compound (log P = 2.01). The biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT. A detailed comparative pharmacokinetic study performed for ¹⁶⁶Ho cation and [¹⁶⁶Ho]-TPP performed up to 24 h. The complex is mostly washed out from the circulation through kidneys and in less extends from the liver. The kidney:blood, kidney:liver and kidney:muscle ratios 4 h post injection were 14, 3.6 and 7.38 respectively.