Body Radioactivity Research Articles

Chemical, radiochemical and biological studies of Sm and Ho complexes of H4dota analogues containing one methylphosphonic/phosphinic acid pendant arm

AbstractThis work intends to investigate samarium and holmium complexes with a set of H4dota‐analogues bearing methylphosphonate/methylphosphinic acid pendant arms (H5do3ap, H5do3apPrA and H4do3apABn) as new bifunctional ligands for radiolanthanide targeted therapy. Radiolanthanide complexes of these ligands were prepared and evaluated and thermodynamic solution studies were also performed to get a better insight on the radiochemical results. The radiocomplexes were quantitatively prepared, are hydrophilic and negatively charged. They present a high in vitro and in vivo stability, a low plasma protein binding and a rapid clearance from the main organs with a high rate of whole body radioactivity excretion. Stability constants with Sm(III) and Ho(III) were determined by potentiometry and the values found are very high for all the ligands. Actually, they are similar to those of H4dota for the phosphinate analogues and even higher for the phosphonate ligand, being the constants similar to those with other lanthanide(III) ions. The effect of methylphosphorus acid pendant arms functionalization and the use of these ligands as bifunctional chelate agents are discussed. Copyright © 2009 John Wiley & Sons, Ltd.

Human Brain Imaging and Radiation Dosimetry of 11C-N-Desmethyl-Loperamide, a PET Radiotracer to Measure the Function of P-Glycoprotein

P-glycoprotein (P-gp) is a membrane-bound efflux pump that limits the distribution of drugs to several organs of the body. At the blood-brain barrier, P-gp blocks the entry of both loperamide and its metabolite, N-desmethyl-loperamide (N-dLop), and thereby prevents central opiate effects. Animal studies have shown that (11)C-dLop, compared with (11)C-loperamide, is an especially promising radiotracer because it generates negligible radiometabolites that enter the brain. The purposes of this study were to determine whether (11)C-dLop is a substrate for P-gp at the blood-brain barrier in humans and to measure the distribution of radioactivity in the entire body to estimate radiation exposure. Brain PET scans were acquired in 4 healthy subjects for 90 min and included concurrent measurements of the plasma concentration of unchanged radiotracer. Time-activity data from the whole brain were quantified using a 1-tissue-compartment model to estimate the rate of entry (K(1)) of radiotracer into the brain. Whole-body PET scans were acquired in 8 healthy subjects for 120 min. For brain imaging, after the injection of (11)C-dLop the concentration of radioactivity in the brain was low (standardized uptake value, approximately 15%) and stable after approximately 20 min. In contrast, uptake of radioactivity in the pituitary was about 50-fold higher than that in the brain. The plasma concentration of (11)C-dLop declined rapidly, but the percentage composition of plasma was unusually stable, with the parent radiotracer constituting 85% of total radioactivity after approximately 5 min. The rate of brain entry was low (K(1) = 0.009 +/- 0.002 mL.cm(-3).min(-1); n = 4). For whole-body imaging, as a measure of radiation exposure to the entire body the effective dose of (11)C-dLop was 7.8 +/- 0.6 muSv/MBq (n = 8). The low brain uptake of radioactivity is consistent with (11)C-dLop being a substrate for P-gp in humans and confirms that this radiotracer generates negligible quantities of brain-penetrant radiometabolites. In addition, the low rate of K(1) is consistent with P-gp rapidly effluxing substrates while they transit through the lipid bilayer. The radiation exposure of (11)C-dLop is similar to that of many other (11)C-radiotracers. Thus, (11)C-dLop is a promising radiotracer to study the function of P-gp at the blood-brain barrier, at which impaired function would allow increased uptake into the brain.

Dynamics of lipid accumulation by the fat body of Rhodnius prolixus: The involvement of lipophorin binding sites

In insects, lipids are stored in the fat body, mainly as triacylglycerol (TAG). In Rhodnius prolixus, a hematophagous hemipteran, lipids are accumulated after blood meal to be used later on. In adult females, at the second day after feeding, the amount of TAG was 57±17μg/fat body, it increased almost five times and at fourth day it was 244±35μg/fat body. TAG content remained constant until day 13, but it then decreased and, at day 20th it was very low (31±4.9μg/fat body). Radiolabeled free fatty acid was used to follow lipid accumulation by the fat body, as it was previously shown that, in R. prolixus, injected free fatty acids associate with lipophorin, a major hemolymphatic lipoprotein. 3H-palmitic acid was injected into the hemocoel of R. prolixus females. It disappeared from the hemolymph very rapidly, and radioactivity was incorporated by the fat body. Sixty minutes after injection, radioactivity in the fat body was found mainly in TAGs. The capacity of the fat body to incorporate fatty acids from the hemolymph varied according to the days after blood meal, and it was maximal around the fourth day. Lipophorin binding to specific sites in fat body membrane preparations also showed variation at different days. When membranes obtained from insects at the second, fifth and tenth days were compared, binding was highest at fifth day after feeding.

Body radioactivity and radiation dose from 40K in Bangladeshi subjects measured with a whole-body counter

A group of subjects of Bangladeshi adults from both sexes were studied for internal radioactivity and effective dose by measuring the whole-body activity of naturally occurring 40K using a whole-body counter. The mean activity concentration in the whole body and effective dose due to naturally occurring 40K for the average male were found to be 2.0 +/- 0.4 Bq x g(-1) and 100 +/- 26 microSv x y(-1), respectively and those for the average female were 1.7 +/- 0.3 Bq x g(-1) and 100 +/- 20 microSv x y(-1), respectively. The mean activity concentration in the whole body and effective dose for both sexes were 1.9 +/- 0.4 Bq x g(-1) and 100 +/- 25 microSv x y(-1), respectively. The effective dose from 40K for subjects is below the value reported by the UNSCEAR.

Biological evaluation of 153Sm and 166Ho complexes with tetraazamacrocycles containing methylcarboxylate and/or methylphosphonate pendant arms

153Sm and 166Ho complexes with two series of tetraazamacrocyclic ligands containing methylcarboxylate and/or methylphosphonate pendant arms were synthesized and their charge, lipophilicity, protein binding and in vitro and in vivo behaviour evaluated. The first series has the same backbone, a 14-membered tetraazamacrocycle containing a pyridine unit with different pendant arms, namely methylcarboxylates (ac3py14) or methylphosphonates (MeP2py14 and P3py14). The second series comprises 12- to 14-membered tetraazamacrocycles having methylcarboxylates and/or methylphosphonates as pendant arms (trans-DO2A2P, TRITA, TRITP, TETA and TETP). The 153Sm/166Ho complexes with the 14-membered tetraazamacrocycles containing the pyridine unit are neutral, hydrophilic, have a significant plasmatic protein binding, are unstable in vivo and present a slow rate of radioactivity excretion and high hepatic retention. 153Sm/166Ho complexes with the 12- to 14-membered tetraazamacrocycles are quantitatively prepared, except those with TETP. These complexes are hydrophilic, have an overall negative charge and present a medium to low plasmatic protein binding. The 153Sm/166Ho- trans-DO2A2P, 153Sm/166Ho-TRITA and 166Ho-TRITP complexes are stable in vitro and in vivo, presenting a rapid clearance from main organs and a high rate of whole body radioactivity excretion. Biological profile of 153Sm/166Ho-TRITA complexes makes them promising candidates for therapy when conjugated to a biomolecule, while 166Ho-TRITP is potentially useful for bone targeting due to its considerable uptake by bone.

Artificial radioactivity in human body and the environment

The 137Cs and 90Sr fallout in Finland and the content of these nuclides in milk samples, water reservoirs, fishes, and human bodies were measured.

High-Dose Myeloablative Zevalin Radioimmunotherapy with Tandem Stem-Cell Autografting Has Promising Activity, Minimal Toxicity and Full Feasibility in an Outpatient Setting.

Background: Because of severe toxicity, in particular mucositis, neutropenia and thrombocytopenia, myeloablative regimens with stem cell support can be safely delivered only to clinically fit and younger pts, require prolonged hospitalization, and have a limited impact in the therapy of NHL. With the aim of rendering high-dose chemotherapy a well tolerated and widely applicable regimen, we carried out a pilot study using high-dose Zevalin with tandem stem-cell support in a prospective cohort of refractory or relapsed NHL patients.Methods: From June 2004 through June 2006, 29 overall NHL patients entered into the study (DLBCL, n=11; follicular, n=10; mantle cell, n=3; small lymphocytic, n=4; Richter syndrome, n=1). Median age was 62 yrs (29–76). The median number of prior chemotherapy regimes was 2 (1–4). Prior to Zevalin, all patients received 3 cycles of standard-dose salvage chemotherapy (DHAP or CHOP, as appropriate), followed by one cycle of high-dose cyclophosphamide plus rituximab, and one cycle of high-dose cytarabine and rituximab, at patient-adapted doses. Hematopoietic stem cells were harvested from the peripheral blood during the post-cyclophosphamide and/or the post-cytarabine recovery phase, and tested for MRD. Zevalin was administered at 0.8 mCi/kg (n=13 pts) or 1.2 mCi/kg (n=16 pts), respectively, and followed by tandem autografting of CD34+ on day +7 and an on day +14, respectively. The latter procedure was performed late, when the radiation absorbed dose to the reinfused stem cells was estimated to be less than 5cGy. In addition, all patients received on day +7 a limited amount (0.8–4.3 x 106/kg) of CD34+ cells. The aim of this early reinfusion, performed in the presence of myelotoxic levels of body radioactivity, was to foster a rapid albeit transient hematopoietic recovery, thus reducing the extend and duration of severe post-Zevalin pancytopenia.Results: Grade 4 neutropenia was observed in 13 pts (45%), and lasted a median of 4 days only (1–14). Grade 4 thrombocytopenia occurred in 19 pts (65%) for a median duration of 5 days (1–14). Fifteen patients (52%) required platelet transfusions (median 2, range 1–6), and 14 pts (48%) received 1 RBC transfusion each. No extra-hematologic toxicity was observed except for mild nausea in 17% of the patients, and all but 3 patients were cared for as outpatients. The 3 hospital admissions lasted 2, 4 and 11 days respectively, and were required for FUO that resolved upon antibiotic administration. Bone marrow analysis performed at 6 (n=5 pts) and 12 months (n=10 pts) showed in all a normal karyotype and a colony growth comparable to controls (NHL pts autografted following BEAM chemotherapy). After a median follow-up of 12 months, the 2-yr OS rate was 87% for indolent and 85% for aggressive lymphoma pts, respectively, while the EFS rate was 55% and 77%, respectively.Conclusions: High-dose Zevalin with tandem stem-cell transplantation was minimally toxic in this pretreated and elderly patient population, proved fully applicable in an outpatient setting, and showed promising activity. Its upfront inclusion as consolidation step after induction chemotherapy warrants a prospective comparison with R-CHOP, in particular in elderly pts with aggressive NHL.

Evaluation of 99mTc-MAG 3-annexin V: influence of the chelate on in vitro and in vivo properties in mice

We conjugated mercaptoacetyltriglycine (MAG 3) to rh-annexin V to permit radiolabeling with 99mTc in an effort to decrease the high kidney and liver accumulation observed for 99mTc-labeled Hynic-annexin V. The 36-kDa protein was conjugated at a 5:1 molar ratio with NHS-MAG 3 in HEPES buffer pH 7.8 at room temperature, then quenched with glycine and purified by dialysis. The biopotency of the resulting MAG 3-annexin was similar to that of Hynic-annexin as determined by a sensitive red blood cell membrane affinity binding assay and a surface plasmon resonance (SPR) assay. The 99mTc radiolabeling of MAG 3-annexin resulted in radiochemical yields of 90% under mildly basic pH conditions. Biodistribution data in normal mice clearly showed a significant decrease in kidney and liver uptake at 1 h postinjection for the 99mTc MAG 3-annexin compared to the 99mTc Hynic-annexin (from 24% ID to 4% ID for the liver, and 45% ID to 15% ID for the kidneys, respectively). Autoradiography of the kidneys showed retention of radioactivity in the collecting tubules following administration of both labeled annexins. The 99mTc MAG 3-annexin biodistribution was also characterized by a lower retention of radioactivity in the whole body, but with small intestine accumulation over fivefold higher than observed with 99mTc Hynic-annexin. These findings show a definite improvement in renal and hepatic clearance of the MAG 3 radioligand. However, due to the increased radioactivity uptake in the small intestines, the early in vivo detection of ongoing apoptosis in the lower abdomen might be more difficult with 99mTc MAG 3-annexin. Nevertheless, 99mTc MAG 3-annexin may be an attractive alternative to 99mTc Hynic-annexin for the in vivo imaging of phosphatidylserine receptors.

Marrow irradiation with high-dose 153Samarium-EDTMP followed by chemotherapy and hematopoietic stem cell infusion for acute myelogenous leukemia

In four patients, aged 15 – 20 years, with high-risk acute myeloid leukemia (AML), high-dose samarium 153-labelled ethylenediaminetetramethylenephosphonate (153Sm-EDTMP) was used for targeted marrow irradiation before preparative chemotherapy conditioning regimens and allogeneic (three patients) or autologous (one patient) hematopoietic stem cell transplantation. The dose of 153Sm-EDTMP was 703 MBq/kg (n = 1) or 1110 MBq/kg (n = 3). No side-effects occurred during the 30-min infusion of 153Sm-EDTMP. Samarium – melphalan regimens were given to three patients; one had 153Sm-EDTMP – busulfan + cyclophosphamide. Total body radioactivity was below the 133 MBq safe limit before infusion of stem cells (day 14 after 153Sm-EDTMP). No hemorrhagic cystitis, nephrotoxicity or serious infections occurred. Leukocyte engraftment (white blood cell count >0.5×109/l) occurred between 12 and 23 days after stem cell infusion (mean of 17 days). Complete cytogenetic and morphologic remission of AML was evident on follow-up marrow aspirate and biopsy specimens from all patients. In two of the four study patients, the disease remains in complete remission and the patients have an excellent quality of life (Eastern Cooperative Oncology Group performance status 0; no medications) and no organ toxicity more than 2 years and more than 4 years, respectively, after their blood and bone marrow transplantations. Thus, in adolescents and adults, 153Sm-EDTMP may provide a relatively simple and effective means for using irradiation to eliminate AML within the marrow.

Reduced Penetration Rate of Pyraclofos into Housefly, Musca domestica, as a Resistance Mechanism

Ethylacetate was found to be suitable for washing pyraclofos from the insect body in experiments to determine the role of the cuticle in the penetration of pyraclofos into the body, and was recommended as a favorable solvent to study housefly resistance to pyraclofos. Three ml of ethylacetate washed off 99% of pyraclofos from the housefly body surface. The penetration through integument played an important role in resistance mechanism of the housefly to pyraclofos. There were considerable differences in penetration rate, excretion rate, and metabolism of the insect body between the resistant (YBOL) and susceptible (SRS) strains of housefly. In penetration study, the YBOL (resistant) strain showed a slightly greater inhibition of penetration than the SRS strain during 1 h after treatment at both the 8, 000-dpm and 4, 000-dpm treatments. Therefore, the reduced penetration rate of pyraclofos is one of the resistance mechanisms in the YBOL strain of housefly even though there were no significant differences of radioactivity between the YBOL and SRS strains after 2 h. For both 8, 000-dpm and 4, 000-dpm treatments, radioactivity in the YBOL surface extract was somewhat higher than in that of SRS, while radioactivity in the housefly body of SRS was higher than that of YBOL. Excretion rate was faster in the resistant housefly. This suggests that metabolic process might be also one of the resistance mechanisms of housefly to pyraclofos.

Amyloid plaque imaging agent [C-11]-6-OH-BTA-1: biodistribution and radiation dosimetry in baboon

The amyloid neuritic plaque is considered to be a toxic collection of amyloid-ss protein found in brain tissue in Alzheimer's disease. A neutral analogue of the amyloid-binding thioflavin-T (BTA), has been radiolabeled as [C-11]-6-OH-BTA-1. It crosses the blood brain barrier, and is a promising tracer for imaging plaques in vivo using positron emission tomography. We now report the biodistribution and dosimetry of [C-11]-6-OH-BTA-1 in baboons. Four 2-hour whole body studies were acquired in an ECAT ACCEL camera in two baboons after the bolus injection of [C-11]-6-OH-BTA-1. After 3.5 minute transmission scans performed per bed position prior to injection, emission scans were collected in 2-D mode over five bed positions. Regions of interest (ROI) were drawn around the brain, left and right lungs, heart, liver, gall bladder, left and right kidneys, spleen and urinary bladder. Since no fluid was removed from the baboons, total body radioactivity was calculated using the injected dose and a calibration factor determined from a cylinder phantom. The area under the curve (AUC) for each ROI was determined by trapezoidal integration of the first few points with subsequent points fit by a decreasing monoexponential. The AUC was then divided by counts in the total body, and resulting residence times were entered into the MIRDOSE3 program. The animals tolerated the procedure well. The ligand was eliminated via the hepatobiliary and renal systems. In the adult male and female reference the gallbladder received the highest estimated radiation dose and was the critical organ (3.9E-02 mGy/MBq and 4.3E-02 mGy/MBq respectively). In the United States, the absorbed dose to the gallbladder would limit [C-11]-6-OH-BTA-1 administered with the approval of a Radioactive Drug Research Committee (RDRC) to a single injection of 1295 MBq (35 mCi) in the adult male, and 1314 MBq (35 mCi) in the adult female.

Gemcitabine Radiosensitization after High-Dose Samarium for Osteoblastic Osteosarcoma

Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 +/- 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after 153Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m2) in combination with 153Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m2/d x 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

Gemcitabine radiosensitization after 153Sm-EDTMP (quadramet) bone-seeking radioisotope therapy for osteoblastic lesions of osteosarcoma: Activity and principles

8534 Background: Osteoblastic metastases can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose 153Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP; Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Methods: Fourteen patients with osteoblastic lesions of osteosarcoma were treated. With high-dose 153Sm-EDTMP (30 mCi/kg) and stem cell support. Gemcitabine was administered 1 day after samarium. Imaging studies used to assess response. Results: The residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 +/− 0.4 mCi; range 0.67–1.8 mCi). Expected cytopenias from skeletal binding of the radiopharmaceutical occurred within 14 days. Peripheral blood progenitor cells (PBPC) were infused 2 weeks after samarium in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after PBPC in 11/11 patients. Toxicity from the daily gemcitabine regimen (250 mg/M2/day x 5) was excessive (grade 3 mucositis; N=1). Toxicity from a single infusion of gemcitabine (1500 mg/M2) in combination with 153Sm-EDTMP was minimal (pancytopenia). There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6–8 week follow-up there were 6 PR, 2 mixed responses, and 6 patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Conclusions: High-dose 153Sm-EDTMP + gemcitabine has activity in osteoblastic osteosarcoma lesions, but recurrence is very common. Other strategies such as repeated standard doses of samarium with gemcitabine and/or use of additional measures of local and systemic control should be considered for more prolonged control of osteoblastic metastases. No significant financial relationships to disclose.

Development of wavelet de-noising technique for PET images

Positron emission tomography (PET) imaging provides the functional information and precise physiological uptake of radioactivity in a patient's body. But the shortcoming of PET is low signal to noise ratio (SNR) due to photon noise. The noise may influence image quality, and cause the mistake of clinical interpretation. The purpose of this research is to develop a wavelet de-noising technique to reduce the noise of PET images. By processing the image through the optimum wavelet parameters we selected, we keep the resolution and contrast but reduce almost half of coefficient of variation in the region of interest of PET images.

188Re-labeled bisphosphonates as potential bifunctional agents for therapy in patients with bone metastases

Two new bisphosphonates have been examined for their ability to bind 188Re and deliver it selectively to bone. The bisphosphonates are prototype compounds with potential to deliver rhenium radionuclides and a second therapy modality to bone metastases. A conjugate between diethylenetriaminepentaacetic acid and bisphosphonate (DTPA/BP) and a conjugate between 5-fluorouracil and bisphosphonate (5-FU/BP) were prepared and labeled at high radiochemical purity with 188Re and biodistribution studies were carried out in normal Balb/C mice. The compounds showed rapid blood clearance and elimination from soft tissues with substantial retention of activity in the bone comparable to 188Re-hydroxyethylidine diphosphonate used as a control. At 8 h bone activity was 3.51% of injected dose for 188Re-DTPA/BP and 6.38% of injected dose for 188Re-5-FU/BP representing 69.6% and 80.6% of total body radioactivity, respectively. The two compounds show the potential for combination therapy of painful bone metastases.

Biodistribution and radiation dosimetry of [ 11C]DASB in baboons

Objective The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [ 11C]DASB ([ 11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [ 11C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183±5 MBq/2.3±1.0 nmol of [ 11C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6×10 −2 mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [ 11C]DASB. In the United States, the absorbed dose to the lungs would limit [ 11C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female.

Database of calculated values of retention and excretion for members of the public following acute intake of radionuclides.

Intakes of radionuclides can be estimated from measurements of radioactivity in the whole body or in specific organs or in excreta by comparing them with predicted retention or excretion data calculated using standard biokinetic models. For occupational exposure monitoring, data are presented by ICRP for 29 radionuclides in Publication 78 (1997) and by the authors for 42 radionuclides as electronic look-up tables in Microsoft Excel. In the present work, values of retention and excretion were computed for selected radionuclides inhaled or ingested by members of the public. Graphs were constructed from the computed results showing the predicted monitoring data as functions of time following acute intakes of radionuclides. A graphical database was assembled on the Web site http//www.nirs.go.jp/RPD/ to provide a tool for the interpretation of bioassay measurements.

99mTc-N, N′-bis(aminoethyl)propanediamine hexaacetic acid (BPHA): a glomerular filtration agent similar to 99mTc-DTPA

Investigations on the biodistribution of 99mTc-BPHA in normal and probenecid treated mice and a comparison with 99mTc-DTPA injected mice suggested that 99mTc-BPHA is also a glomerular filtration agent. Whole body radioactivity measurements in mice and rabbits after administration of 99mTc-BPHA showed negligible whole body radioactivity at 24 h. Excellent kidney images both in rabbits and a human volunteer were obtained. The significance of higher GFR estimates using 99mTc-BPHA compared to 99mTc-DTPA is discussed.

Caesium retention during pregnancy in mice

The effect of pregnancy on caesium retention in mice was assessed. Fifteen female mice were injected with caesium-137 solution intraperitoneally and measurements of body radioactivity were performed. For the control group of mice ( n=8), caesium retention could be adequately described, for the time period from day T=7 to 26 post-injection, by a two exponential model, where 90% of caesium was eliminated by a component with a biological half-time of (2.83±0.78) d and 10% by a component with a biological half-time of (16.3±7.3) d. However, an alteration of caesium elimination rate, which affects the component with the longer half-time was observed in the group of pregnant mice ( n=7). The observed effect was a decrease in excretion rate, in contrast to recent human observations where an increase was found. This difference in mice is associated with changes in metabolic rate, and, to a first approximation, is related to the gain in mass during pregnancy.

Early detection of liposome brain localization in rat experimental allergic encephalomyelitis.

Blood-brain barrier (BBB) permeability increases prior to the development of clinical signs in early-stage multiple sclerosis (MS). Detection of subtle changes would thus be helpful for diagnostic purposes and rapid therapeutic decisions before new episodes. Since multiple sclerosis and experimental allergic encephalomyelitis (EAE) have numerous common features, in particular BBB-permeability characteristics, and since we have previously shown that BBB localization is disturbed by tumors, embolism, and mannitol injection, we investigated BBB-liposome permeability in an EAE rat model. Twenty young male Lewis rats received a single intradermal inoculation of guinea-pig spinal cord. The effect of the Freund's adjuvant and spinal cord alone on brain permeability were also assessed. In order to compare solution permeability and liposome localization, radioactive liposomes and, 1 h later, 99mTc-DTPA were injected intravenously. Scintigraphic acquisitions were obtained to follow the biodistribution of radioactivity in the whole body. Each rat was subjected to a first examination before inoculation and then every two days until completion and may be considered as its own control. EAE induced a previously unreported increase in global-body permeability, probably due to inflammation. Liposome brain localization and brain/heart ratio were significantly different between normal animals and those with early-stage EAE (before appearance of clinical signs) and distinguished between different disease stages in clinically patent EAE. The index of disease progression was modified earlier than with 99mTc-DTPA injection. One explanation may be particle pick-up by circulating macrophages, which cross the BBB during this pathology. For clinical applications, experiments must be confirmed on models more reliable for human multiple sclerosis.