MASAHIRO NATSUHORI
@kitasato-u.ac.jp
Veterinary medicine
Kitasato University
1992/04/01-1993/03/31 Oda College of NutritionAnatomical physiologyadjunct instructor lecturer
1993/04/01-1996/03/31 JSPS FellowshipResearch fellow
1996/04/01-1999/04/30 Kitasato University School of Veterinary Medicine and Animal SciencesVeterinary RadiologyResearch assistant
1999/04/01-Present Iwate UniversityFaculty of Agricultureadjunct instructor lecturer
1999/05/01-2006/06/30 Kitasato University School of Veterinary Medicine and Animal SciencesVeterinary RadiologyAssistant Professor
2006/07/01-2007/06/30University of TennesseeFaculty of Veterinary MedicineResident (Veterinary radiology)
2007/04/01-2019/03/31Tokyo University of Agriculture and TechnologyFaculty of Agricultureadjunct instructor lecturer
2007/07/01-2008/03/31JARMeC; Japan Animal Referral Medical CenterRadiologyDean
2008/04/01-2013/03/31JARMeC; Japan Animal Referral Medical CenterDirector and Dean of Radiology
2013/04/01-PresentKitasato UniversitySchool of Veterinary MedicineProfessor
EDUCATION
1991/06/30 Utrecht UniversityFaculty of Veterinary Medicine as a Research fellow
1992/03/31 Graduated Tokyo University of Agriculture and TechnologyFaculty of AgricultureDepartment of Veterinary Medicine
1995/06/30 Utrecht UniversityFaculty of Veterinary MedicinePost as a doctoral trainee
1996/03/31 CompletedGifu UniversityUnited Graduate School, Division of Veterinary Medicine PhD course
RESEARCH INTERESTS
Radiology, Diagnostic imaging, Radiation therapy, Environmental radiology, Pharmacokinetics
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Daiki Horikami, Naoya Sayama, Jun Sasaki, Haruka Kusuno, Hiroyuki Matsuzaki, Akane Hayashi, Tatsuro Nakamura, Hiroshi Satoh, Masahiro Natsuhori, Keiji Okada,et al.
Springer Science and Business Media LLC
AbstractNuclear plant accidents can be a risk for thyroid cancer due to iodine radioisotopes. Near the Fukushima Daiichi nuclear power plant, cattle were exposed to radiation after the accident occurred in May 2011. Here we estimated the total radiation exposure to cattle thyroid and its effects on thyroid function. Until October 2016, the estimated external exposure dose in Farm A was 1416 mGy, while internal exposure dose of 131I, 134Cs, and 137Cs were 85, 8.8, and 9.7 mGy in Farm A and 34, 0.2, and 0.3 mGy in Farm B, respectively. The exposed cattle had thyroid with relatively lower weight and lower level of stable iodine, which did not exhibit any pathological findings. Compared with the control, the plasma level of thyroid-stimulating hormone (TSH) was higher in Farm A cattle born before the accident, while the plasma thyroxine (T4) was higher in Farm A cattle born after the accident, suggesting that exposed cattle showed slight hyperactivation of the thyroid gland. In addition, Farm A cattle have higher level of cortisol, one of the anterior pituitary gland-derived hormones. However, we did not observe a causal relationship between the radiation exposure and cattle thyroid.
Sumi Yokoyama, Norio Tsujimura, Makoto Hashimoto, Hiroshi Yoshitomi, Masahiro Kato, Tadahiro Kurosawa, Hideo Tatsuzaki, Hiroshi Sekiguchi, Yasuhiro Koguchi, Koji Ono,et al.
Korean Association for Radiation Protection
Background: In Japan, new regulations that revise the dose limit for the lens of the eye (hereafter the lens), operational quantities, and measurement positions for the lens dose were enforced in April 2021. Based on the international safety standards, national guidelines, the results of the Radiation Safety Research Promotion Fund of the Nuclear Regulation Authority, and other studies, the Working Group of Radiation Protection Standardization Committee, the Japan Health Physics Society (JHPS) developed a guideline for radiation dose monitoring for the lens.Materials and Methods: The Working Group of the JHPS discussed the criteria of non-uniform exposure and the management criteria set not to exceed the dose limit for the lens.Results and Discussion: In July 2020, the JHPS guideline was published. The guideline consists of three parts: main text, explanations, and 26 examples. In the questions, the corresponding answers were prepared, and specific examples were provided to enable similar cases to be addressed.Conclusion: With the development of the guideline on radiation dose monitoring of the lens, radiation managers and workers will be able to smoothly comply with revised regulations and optimize radiation protection.
Ichiro Yamaguchi, Kazuhiko Inoue, Masahiro Natsuhori, Chryzel Angelica B. Gonzales, Hiroshi Yasuda, Yasuhiro Nakai, Minoru Miyake, and Harold M. Swartz
MDPI AG
We applied a non-destructive tooth dosimetry technique using L-band electron paramagnetic resonance (EPR) to assess radiation doses in cattle due to the Fukushima Daiichi Nuclear Power Station (FDNPS) accident, which occurred 10 years ago. The radiation exposure of cattle in the area affected by the FDNPS accident was estimated retrospectively with X-band and L-band EPR devices. Characteristic radiation-induced EPR signals were obtained from the teeth of the cattle in Fukushima, confirming their exposure. The estimated doses to the teeth were found to be consistent with the dose trends estimated for individual cows, while considerable uncertainties were seen in the doses of some tooth samples. This variation might be due to errors in the accuracy of the method but also might reflect the actual exposure because the cattle may have been exposed to higher areas of radioactivity in their quest for food and/or due to irradiation from absorption of the isotopes with localization in or near the teeth. However, at a minimum, these results confirm that L-band EPR can be used for non-destructive qualitative assessment of radiation exposure to animals using their teeth, which could be very valuable. Possible causes of the uncertainties should be investigated to enhance the value of the use of this technique.
R.J. Pentreath, K.E. Applegate, K.A. Higley, K. Peremans, M. Natsuhori, E. Randall, and J. Gambino
SAGE Publications
At the request of the Main Commission of the International Commission on Radiological Protection (ICRP), Task Group 107 (TG107) was set up to consider the issue of radiological protection of the patient in veterinary medicine. TG107, who authored this article, brought together information relating to the use of diagnostic imaging and radiation oncology in veterinary medicine. A number of specific areas were identified that appeared to be appropriate for attention by ICRP. These included the use of dose quantities and units, the need for re-evaluation of stochastic and deterministic risks from ionising radiation in animals, and the growing use of imaging and therapeutic equipment for animals that is little different from that available to humans. TG107 unanimously recommended that it was both appropriate and timely for ICRP to consider and advise on these issues, and the Main Commission agreed. This paper summarises the findings of TG107.
Itaru Sato, Jun Sasaki, Hiroshi Satoh, Masahiro Natsuhori, Takahisa Murata, and Keiji Okada
Springer Science and Business Media LLC
Since the Fukushima nuclear accident in 2011, various abnormalities have been reported in animals living in the contaminated area. In the present study, we examined DNA damage in cattle living in the "difficult-to-return zone" by 8-hydroxy-2′-deoxyguanosine, comet, and micronucleus assays using their peripheral blood. The radiation exposure dose rate at the sampling time was approximately 0.25 or 0.38 mGy/day and the cumulative dose was estimated at approximately 1000 mGy. Significant increase in DNA damage was not detected by any of the three methods. As DNA damage is a stochastic effect of radiation, it might be occurring in animals living in the contaminated area. However, the present results suggest that radiation-induced DNA damage in the cattle did not increase to the level detectable by the assays we used due to the low dose rate in this area.
Azumi Todaka, Shin Toyoda, Masahiro Natsuhori, Keiji Okada, Itaru Sato, Hiroshi Sato, and Jun Sasaki
Elsevier BV
Abstract ESR tooth enamel retrospective doses were obtained for teeth of 16 cattle bred in the two ranches located in the area contaminated by Fukushima Dai-ichi Nuclear Power accidents in 2011. The obtained doses are up to 1.0 Gy for cattle bred in both two ranches. The doses obtained for cattle in Omaru ranch, with higher contamination, are roughly consistent with the cumulative environmental dose. High dose values are also obtained for those in Okuma-Ikeda ranch, with lower contamination, which are not consistent with the cumulative environmental dose, but can be explained by the records that they were once released from the ranch and were captured in highly contaminated area. The ESR tooth enamel dose distribution within jaws were examined for two cattle of 12 years and 7 years old. The older cattle shows rather uniform distribution of the doses with slight increase in frontal teeth while the younger shows larger values in molar teeth, being consistent with the time difference in permanent tooth eruption (enamel formation). These results indicate that the cattle tooth enamel ESR dosimetry works practically and would be useful in estimating the actual environmental doses.
Shin Toyoda, Mika Murahashi, Masahiro Natsuhori, Setsuro Ito, Alexander Ivannikov, and Azumi Todaka
Oxford University Press (OUP)
The method of electron spin resonance (ESR) tooth enamel dosimetry was successfully applied to cattle molar teeth exposed in the accident of Fukushima Dai-ichi atomic power plants. Total of 10 samples from 5 cattle were examined and the doses were retrospectively reconstructed to be up to 1.2 Gy (enamel dose). The dose values are roughly consistent with those estimated from the monitored environmental dose rate and the durations of the exposure. This first successful result on ESR reconstruction of doses in the actual radiation accident indicates that ESR tooth enamel dosimetry with cattle is practically useful in the dose range of ~1 Gy.
Jun Sasaki, Megumi Uehara, Itaru Sato, Hiroshi Satoh, Yoshitaka Deguchi, Hiroyuki Chida, Masahiro Natsuhori, Takahisa Murata, Kenji Ochiai, Kumiko Otani,et al.
Wiley
To study the effect of ionizing radiation on thyroid glands, 66 Japanese Black cattle residing in the restricted area of the Fukushima Daiichi Nuclear Power Plant in 2013-2017 were pathologically examined. There were no clinical symptoms of thyroid disease in these cattle. Three cases of goiter and seven of atrophy were found in two among the four farms examined. Cases of goiter exhibited normal morphological structure without mass or nodule formation in thyroid glands. Cellular atypia or capsular invasion of the follicular epithelium was absent. The estimated integrated dose of external radiation in goiter cases ranged from maximum 797 mSv to minimum 24 mSv. All lobules in the seven atrophic thyroid glands were affected, but pathological findings, such as inflammatory cell infiltration or stromal fibrosis, were not observed. The estimated integrated dose of external radiation in atrophic thyroids ranged from maximum 589 mSv to minimum 8 mSv. Immunohistochemical analysis of anti-nitroguanosine and the TUNEL method in goiter and atrophic thyroid glands did not reveal any positive findings. The present study indicates that there was no significant relationship between a radiation effect and pathological findings in any thyroid glands.
Kazuhiko Inoue, Ichiro Yamaguchi, and Masahiro Natsuhori
Springer Singapore
Itaru Sato, Jun Sasaki, Hiroshi Satoh, Masahiro Natsuhori, Takahisa Murata, and Keiji Okada
Wiley
Blood and urine were compared to clarify which is a better sample for estimating the concentration of radioactive cesium in muscles of live cattle. The most probable concentration of 137 Cs in muscles was 21.0 times that in blood, and the error of this estimation was 28%. The concentration of 137 Cs in blood was estimated accurately using urine samples. The estimation error did not increase so much (33%), even when the concentration of 137 Cs in muscles was estimated using urine samples. On the other hand, the maximum volume of blood that can be collected with one syringe is 50 ml, whereas it is easy to collect 1,000 ml of urine. It took at least 360 min to confirm that a cow meets the legal standard by inspecting 50 ml of blood. However, with 1,000 ml of urine, a 20 min measurement time was sufficient for this purpose. This difference in the required measurement time is critically important for practical use. In addition, urine can be collected by farmers themselves, whereas the blood collection requires a veterinarian. Therefore, urine is a more convenient and practical sample for estimating the contamination level of live cattle with radioactive cesium.
Itaru Sato, Jun Sasaki, Hiroshi Satoh, Yoshitaka Deguchi, Hiroyuki Chida, Masahiro Natsuhori, Kumiko Otani, and Keiji Okada
Wiley
Abstract White blood cells, especially lymphocytes, are susceptible to radiation exposure. In the present study, red blood cell, total white blood cell, and lymphocyte counts were repeatedly measured in cattle living on three farms located in the “difficult‐to‐return zone” of the Fukushima nuclear accident, and compared with two control groups from unaffected areas. Blood cell counts differed significantly between the two control groups, although almost all the values fell within the normal range. The blood cell counts of the cattle in the “difficult‐to‐return zone” varied across sampling times even on the same farms, being sometimes higher or lower than either of the two control groups. However, neither a statistically significant decrease in blood cell counts nor an increase in the rate of cattle with extremely low blood cell counts was observed overall. The estimated cumulative exposure dose for the cattle on the most contaminated farm was within a range of 500–1000 mSv, exceeding the threshold for the lymphopenia. Because of the low dose rate on these farms, potential radiation damages would have been repaired and have not accumulated enough to cause deterministic effects.
Jun Sasaki, Kayoko Hiratani, Itaru Sato, Hiroshi Satoh, Yoshitaka Deguchi, Hiroyuki Chida, Masahiro Natsuhori, Takahisa Murata, Kenji Ochiai, Kumiko Otani,et al.
Wiley
Fifty-one Japanese black cattle from four farms in the evacuation zone of the Fukushima nuclear accident were examined pathologically during the period, 2013-2016. We found no evidence of a radiation effect on pathological findings in any of these autopsy cases, although nine cases (3.7%) of enzootic bovine leukosis (EBL) and three cases (1.2%) of goiter were diagnosed. Estimated integrating dose of external exposure in EBL cases ranged from a maximum of 1200 mSv to a minimum of 72 mSv. Clinically, five cases showed wobble, dysstasia or paralysis. Exophthalmos was observed in three cases. Macroscopically, enlarged lymph nodes, multiple irregular masses of intra-abdominal and intrapelvic adipose tissue, diffuse thickening of the abomasal submucosa with ulceration, and numerous white nodules of myocardium were observed. Histologically, neoplastic lymphoid cells were extensively proliferated and infiltrated in the lesions. Lymphoid tumor cells showed mature or large lymphoblastic appearance. Immunohistochemically, tumor cells were positive for BLA-36, CD20 and CD5, and negative for CD3. Three cases showed diffuse enlargement of the thyroid gland with no mass or nodule lesion. Histologically, diffuse proliferation of follicular epithelium was observed with preservation of normal structures. There were no malignant findings such as cellular atypia or invasion to capsule.
Seiichi Wada, Nobuhiko Ito, Masamichi Watanabe, Takehiko Kakizaki, Masahiro Natsuhori, Jun Kawamata, and Yoshio Urayama
Public Library of Science (PLoS)
As a result of the 2011 nuclear incident that occurred at the Fukushima Nuclear Power Plant, a large number of abandoned dogs and cats were left within the disaster zone. A small number of these animals were rescued and cared for at shelters. Prior to the dispersal of these animals to their owners or fosterers, we evaluated the degree of internal radiocesium contamination using a specially designed whole-body counter. We conducted 863 non-invasive measurements of gamma rays due to internal radioactive cesium for 68 dogs and 120 cats at one shelter. After plotting graphs of 137Cs density we generated exponential functions of decay from seven dogs and six cats. From the regression formulae, we were able to determine the biological half-lives as 38.2 days for dogs and 30.8 days for cats. We found that in dogs there was a correlation between the biological half-life of radioactive cesium and age. Using our data, we estimated whole-body densities for each cat and dog at the time when they were rescued. We found that there were deviations in the data distributions among the different species, likely due to the timing of rescue, or living habits prior to rescue. A significant correlation was found when extracted feline reproductive organs were analyzed; the coefficients for the estimation of whole-body densities were approximately 7-fold higher than those based on the extracted feline reproductive organs. This may be due to the fact that majority of the radioactive cesium accumulates within muscular tissue with less distribution in other organs. It is possible to plan the appropriate management period in an animal shelter based on the use of the biological half-life of radioactive cesium calculated in this study. We believe that the correlations we uncovered in this work would be of great use for the management of companion animals in the event of a future nuclear accident.
Kiwamu HANAZONO, Shinya FUKUMOTO, Kazuko HIRAYAMA, Kazuaki TAKASHIMA, Yoshihisa YAMANE, Masahiro NATSUHORI, Tsuyoshi KADOSAWA, and Tsuyoshi UCHIDE
Japanese Society of Veterinary Science
Gastrointestinal stromal tumor (GIST), a mesenchymal neoplasm affecting the gastrointestinal tract, shows a variety of clinical behaviors from inactive benign to aggressive malignant in dogs. In this study, the feasibility of using clinically significant ultrasonographic features to predict the metastatic potential of canine GIST was investigated through comparison with actual metastatic incidence and findings of malignancy obtained by postoperative pathological examination. Ultrasonographic features, including large tumor size, irregular margin and heterogeneous internal echogenicity with large hypoechoic areas, related closely with the presence of metastasis as well as a high-risk ranking by the human classification system according to pathological findings. Based on these ultrasonographic features, the potential of metastasis in canine GIST could be preoperatively predicted.
Masami Torikoshi, Yumiko Ohno, Masahiro Natsuhori, Nobuhiko Ito, Kentaro Uesugi, Naoto Yagi, Takanori Tsunoo, Meng De, and Masahiro Endo
Elsevier BV
Abstract Dual energy X-ray CT was carried out with synchrotron radiation at BL20B2 beam line of JASRI/SPring-8. The X-ray beams were vertically magnified by employing an asymmetry Bragg reflection geometry. The field size was about 25 mm×250 mm at the end of the beam line. Porcine eyes and brain and water were used as samples. The DXCT provided the highly accurate information on an electron density; the electron density of water was in agreement of about 0.6% with the theoretical value. Images of the electron density and an effective atomic number had good quality sufficient for medical applications.
Takehiko KAKIZAKI, Nobuyuki HAMADA, Tetsuya SAKASHITA, Seiichi WADA, Takamitsu HARA, Tomoo FUNAYAMA, Tsutomu HOHDATSU, Masahiro NATSUHORI, Tadashi SANO, Yasuhiko KOBAYASHI,et al.
Japanese Society of Veterinary Science
An analysis of ionizing radiation-induced damage in peripheral lymphocytes has been employed to predict the prognosis of radiotherapy in terms of toxicity in normal tissues. Therefore, understanding the sensitivity of lymphocytes to high linear energy transfer (LET)-charged particles would be indispensable for utilizing charged particle therapy in veterinary medicine. However, the availability of such information is very limited. This study aimed to compare the radiosensitivity of feline T lymphocytes to gamma-rays (0.2 keV/microm) and 4 different types of charged particles with LET values ranging from 2.8 to 114 keV/microm. It was observed that the relative biological effectiveness, inactivation cross-section, and isodose-induced apoptosis increased in an LET-dependent manner. On the other hand, no difference in apoptosis frequency was observed in the cells exposed to an isosurvival dose of all the radiation types tested. This is the first study that demonstrates the LET dependence of cell killing and apoptosis induction in feline T lymphocytes. Our results suggest that lymphocytes can be effectively used to predict the prognosis of charged-particle therapy in cat patients.
Takehiko KAKIZAKI, Nobuyuki HAMADA, Tomoo FUNAYAMA, Tetsuya SAKASHITA, Seiichi WADA, Tsutomu HOHDATSU, Masahiro NATSUHORI, Tadashi SANO, Yasuhiko KOBAYASHI, and Nobuhiko ITO
Japanese Society of Veterinary Science
High linear energy transfer (LET) heavy charged particles have previously been applied clinically to human cancer radiotherapy because of their excellent physical properties of selective dose distribution and higher relative biological effectiveness (RBE) for human; however, such an approach has yet to be applied to cat patients. The present study investigates the biological effectiveness of low-LET gamma-rays (0.2 keV/micro m) compared to high-LET carbon ions (114 keV/micro m) in feline T- lymphocyte FeT-J cells. Clonogenic survival analysis revealed that the RBE value of carbon ions was 2.98 relative to a 10% survival dose (D(10)) by gamma-rays, and that the inactivation cross-section in cells exposed to gamma-rays and carbon ions was 0.023 and 38.9 micro m(2), respectively. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) analysis revealed that TUNEL-positive frequency in carbon-irradiation cells is higher than for gamma-irradiated cells against exposure to the same physical doses, but that very little difference in TUNEL-positive frequency is observed between cells exposed to the respective D(10) dose of gamma-rays. Our data thus indicate that carbon ions are more effective for cell killing than gamma-rays at the same physical doses, but kill cells to an extent that is comparable to gamma-rays at the same biological doses. Carbon ion radiotherapy is therefore a promising modality for cat patients.
Takehiko KAKIZAKI, Yukiko YOKOYAMA, Masahiro NATSUHORI, Azusa KARASAWA, Satoshi KUBO, Naoaki YAMADA, and Nobuhiko ITO
Japanese Society of Veterinary Science
Pharmacokinetics (PK) of probenecid including plasma probenecid concentrations, in vitro plasma protein binding properties, and in vivo PK parameters were determined in dogs. Probenecid concentrations were best determined by HPLC, which showed good linearity and good recovery with simple plasma preparation. The quantification limit of probenecid was approximately 50 ng/ml at S/N ratio = 3, by simple procedure with HCl and methanol treatment. Probenecid showed two types of binding characteristics, i.e., high-affinity with low-capacity and low-affinity with high-capacity binding. This result indicated 80-88% of probenecid was bound to plasma protein(s) at observed concentrations (< 80 microg/ml) in vivo at an intravenous dose of 20 mg/kg. Plasma probenecid concentration-time profile following i.v. administration in dogs showed biphasic decline and well fitted a two-compartment open model. The total body clearance was 0.34 +/- 0.04 ml/min/kg, volume of distribution at steady-state was 0.46 +/- 0.07 l/kg, elimination half-life was 18 +/- 6 hr, and mean residence time (MRT) was 23 +/- 6 hr. Since probenecid has been known as a potent inhibitor of renal tubular excretion of acidic drugs and highly binds to plasma proteins, our observation in relation to plasma protein binding and PK parameters will serve as the basic information concerning drug-drug interactions in dogs and in other mammalian species.
Takehiko KAKIZAKI, Nobuyuki HAMADA, Seiichi WADA, Tomoo FUNAYAMA, Tetsuya SAKASHITA, Tsutomu HOHDATSU, Tadashi SANO, Masahiro NATSUHORI, Yasuhiko KOBAYASHI, and Nobuhiko ITO
Oxford University Press (OUP)
We have examined in vitro radiosensitivities and radioresponses to (60)Co gamma-rays irradiation in feline T-lymphocyte cell lines, FeT-J and FL-4. There seemed to be no significant difference in clonogenic survival between the two lines. The mean lethal dose for both was both 1.9 Gy, and surviving fraction at 2 Gy was 0.30 and 0.48 for FeT-J and FL-4 cells, respectively. However, TUNEL assay indicated much higher degrees of apoptosis induction in FeT-J cells (>40%) than in FL-4 cells (<10%) at 4 days after 15 Gy irradiation. Microscopic examination revealed a larger population of multi-nucleate cells in FL-4 cells (60.3%) than in FeT-J cells (16.0%) at 4 days after 15 Gy irradiation, suggesting that a larger ratio of mitotic catastrophe occurred in FL-4 cells. These results suggest that FeT-J is more likely to be induced into apoptosis and FL-4 is more likely to fall into mitotic catastrophe, and eventually necrosis; both of them showed a similar surviving fraction against gamma-rays. The results also indicate that FL-4 cells follow a process other than apoptosis to cell death, suggesting the presence of a regulatory mechanism that may control the relationship between mitotic catastrophe and apoptosis in feline T-lymphocytes.
T. KAKIZAKI, Y. YOKOYAMA, M. NATSUHORI, N. YAMADA, M. HASHIMOTO, K. SATO, N. ITO, and G. B. DANIEL
Wiley
Effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetylytriglycine (99mTc-MAG3) in dogs was investigated before (control), and after 15 min and 24 h of i.v. injection of probenecid (20 mg/kg). Plasma concentration-time profiles of 99mTc-MAG3 were described with a two-compartment open model. Plasma 99mTc-MAG3 clearances (Clp, ml/min/kg) were 7.9 +/- 0.5, 3.3 +/- 0.5 and 4.8 +/- 1.3 in control, 15 min and 24 h after probenecid administration respectively. Similarly, the biological half-lives at elimination phase (t(1/2), h) were 0.61 +/- 0.09, 0.79 +/- 0.11 and 0.74 +/- 0.12, and volumes of distribution at steady state (Vdss, L/kg) were 0.29 +/- 0.04, 0.20 +/- 0.05 and 0.25 +/- 0.06 respectively. The prolonged biological half-life and decreased Vdss decreased Clp significantly. Clp was a function of plasma probenecid concentration based on Michaelis-Menten kinetics. The maximum Clp inhibition (Imax) by probenecid and the plasma probenecid concentration that induced 50% of Imax (I50) were estimated to be 72 +/- 12% and 13 +/- 8 microg/ml respectively. This means that the rest (about 28%) of the Clp is not blocked by probenecid alone, suggesting the possibility of another route(s) of elimination or renal transporters which are independent from probenecid. Moreover, inter-species correlation between Clp of 99mTc-MAG3 and body weight are discussed.