Biodistribution and radiation dosimetry of 11C-harmine in baboons

OBJECTIVE: Monoamine oxidase A is a mitochondrial enzyme which is responsible for the metabolism of catecholamines such as dopamine, norepinephrine, as well as serotonin. This study describes the biodistribution and dosimetry of 11C-harmine, a tracer designed to specifically bind to monoamine oxidase A for positron emission tomography imaging. METHODS: Three baboon studies were acquired using a Seimens ECAT camera. Dynamic whole-body emission scans were collected in two-dimensional mode over a 2 h period after 223-255 MBq of 11C-harmine was injected. Regions of interest were drawn on transmission corrected images to encompass the entire activity in visible organs at each time point. Time-activity data were used to obtain residence times and absorbed radiation dose to various organs and to the entire body. RESULTS: Tracer uptake was greatest in the lungs, followed by kidney, small intestine, liver and brain. The largest absorbed dose based on averaged residence times was found in the lungs (reference adult/female 3.99x10(-2)/5.03x10(-2) mSv x MBq(-1)). CONCLUSION: The lungs are the critical organs for administration of 11C-harmine. For example, in the United States, the absorbed dose to the lungs would limit a single 11C-harmine administration for a research subject with the approval of a Radioactive Drug Research Committee to 1258/999 MBq (34/27 mCi) in the adult male/female. Quantitative measurement of monoamine oxidase A activity in the brain and elsewhere may aid in understanding the pathophysiology of several disease processes including neuroendocrine neoplasms and depression.     

Biodistribution and radiation dosimetry of 11C-WAY100,635 in humans.

Serotonin 1A receptors have been implicated in a variety of conditions including depression, suicidal behavior, and aggression. Dose estimates for current human studies are based on data from rat dosimetry studies. We report the biodistribution and dosimetry of the PET serotonin 1A antagonist 11C-WAY100,635 in humans. METHODS: PET studies of 6 healthy human volunteers (3 male, 3 female) were acquired after a bolus injection of 11C-WAY100,635. Transmission scans of 3.5 min were obtained at each bed position before injection, and emission scans then were collected in 2-dimensional mode over 8 bed positions. Regions of interest were drawn around the brain, left and right lungs, heart, liver, stomach wall, gallbladder, left and right kidneys, spleen, and urinary bladder. Because no fluid was removed from the subjects, whole-body radioactivity was calculated using the injected dose and a calibration factor determined from a cylinder phantom. The area under the curve for each region of interest was determined by trapezoidal integration of the first 3 points, with subsequent points fit by a decreasing monoexponential. The area under the curve was then divided by counts in the whole body, and the resulting residence times were entered into the MIRDOSE3 program. RESULTS: Primary elimination was via kidneys to the urinary bladder. There were no sex differences in organ residence times. The urinary bladder wall was the organ with the highest estimated radiation dose (1.94 x 10(-1) +/- 3.57 x 10(-2) mGy/MBq). Except for the kidney and bladder wall, correlation was good between human dosimetry estimates and estimates reported previously from rats. The human dosimetry was 6.6 and 60.6 times higher in the kidneys and urinary bladder wall, respectively, than estimates from rats. CONCLUSION: The urinary bladder wall is the critical organ for 11C-WAY100,635 in humans. In the United States, according to Radioactive Drug Research Committee guidelines a single dose cannot exceed 300 MBq in a man and 227 MBq in a woman, with up to 3 such injections permitted per annum.     

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 [(11)C]DASB ([(11)C]-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 [(11)C]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 [(11)C]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 x 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 [(11)C]DASB. In the United States, the absorbed dose to the lungs would limit [(11)C]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.     

Biodistribution and radiation dosimetry of [11C]raclopride in healthy volunteers

Purpose This study reports on the whole-body biodistribution and radiation dosimetry of [¹¹C]raclopride, a dopamine D₂ receptor antagonist.Methods In three healthy male volunteers, whole-body scans were performed up to 2 h following i.v. injection of 320±65 MBq [¹¹C]raclopride. Transmission scans (3 min per step, eight or nine steps according to the height of the subject) in 2D mode were used for subsequent attenuation correction of emission scans. Emission scans (1 min per step, eight or nine steps) were acquired over 2 h. Venous blood samples and urine were collected up to 2 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, intestine, lungs, kidneys and liver was fitted to a mono-exponential model, as an uptake phase followed by a mono-exponential washout, for urinary bladder to generate time–activity curves. Using the MIRD method, several source organs were considered in estimating residence time and mean effective radiation absorbed doses.Results Blood pressure and ECG findings remained unchanged after tracer injection. The analysed blood and urine pharmacological parameters did not change significantly after [¹¹C]raclopride injection. The primary routes of clearance were renal and intestinal. Ten minutes after injection, high activities were observed in the gall-bladder, kidneys and liver. High activity was observed in the gall-bladder during the whole study. The kidneys, urinary bladder wall, liver and gall-bladder received the highest absorbed doses. The average effective dose of [¹¹C]raclopride was estimated to be 6.7±0.4 Sv/MBq.Conclusion The amount of [¹¹C]raclopride required for adequate dopamine D₂ receptor imaging results in an acceptable effective dose equivalent, permitting two or three repeated clinical PET imaging studies, with the injection of 222 MBq for each study.     

Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans.

We investigated the biodistribution and radiation dosimetry of the PET amyloid imaging agent (11)C-PIB ((11)C-6-OH-BTA-1) (where BTA is benzothiazole) in humans. Previous radiation exposure estimates have been based on animal experiments. A dosimetry study in humans is essential for a balanced risk-benefit assessment of (11)C-PIB PET studies. METHODS: We used data from 16 different (11)C-PIB PET scans on healthy volunteers to estimate radiation exposure. Six of these scans were dynamic imaging over the abdominal region: 3 covering the upper abdomen and 3 covering the middle abdomen. On average, 489 MBq of (11)C-PIB (range, 416-606 MBq) were injected intravenously, and dynamic emission scans were recorded for up to 40 min. Two subjects had whole-body imaging over the entire body to illustrate the biodistribution. PET brain scans and blood and urine radioactivity measurements from our previous (11)C-PIB studies were also analyzed. Thirteen source organs and the remainder of the body were studied to estimate residence times and mean radiation-absorbed doses. The MIRD method was used to calculate the radiation exposure of selected target organs and the body as a whole. RESULTS: There is a high degree of consistency between our human data and previous biodistribution information based on baboons. In our study, the highest radiation-absorbed doses were received by the gallbladder wall (41.5 microGy/MBq), liver (19.0 microGy/MBq), urinary bladder wall (16.6 microGy/MBq), kidneys (12.6 microGy/MBq), and upper large intestine wall (9.0 microGy/MBq). The hepatobiliary and renal systems were the major routes of clearance and excretion, with approximately 20% of the injected radioactivity being excreted into urine. The effective radiation dose was 4.74 microSv/MBq. CONCLUSION: The established clinical dose of (11)C-PIB required for 3-dimensional PET amyloid imaging has an acceptable effective radiation dose. This dose is comparable with the average exposure expected in other PET brain receptor tracer studies. (11)C-PIB is rapidly cleared from the body, largely by the kidneys. From the viewpoint of radiation safety, these results support the use of (11)C-PIB in clinical PET studies.     

Biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled monocytes in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) involves the accumulation of monocyte-derived macrophages in the affected synovial tissue. This process of cell migration could be portrayed scintigraphically to monitor noninvasively the effects of therapy on the progress of the disease. For this purpose, labeling of purified autologous monocytes with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) at very high specific radioactivity has recently been developed. The aim of this study was to assess the biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled monocytes in adult patients with RA. METHODS: In 8 patients with RA, monocytes were isolated from 100 mL of blood and labeled with 99mTc-HMPAO to a yield of 10 Bq/cell. Multiple whole-body scans were performed up to 20 h after reinjection of an average of 200 MBq of 99mTc-HMPAO-labeled monocytes. Urine and blood samples were collected. The fraction of administered activity in 7 source organs was quantified from the attenuation-corrected geometric mean counts in conjugate views. Radiation-absorbed doses were estimated with OLINDA/EXM software. RESULTS: Autologous monocytes labeled with 99mTc-HMPAO at high intracellular yields showed in vivo kinetics comparable with labeled leukocytes, with initial trapping in the lungs followed by distribution into the liver, spleen, and bone marrow. The radiation-absorbed estimates for 99mTc-HMPAO-labeled monocytes were comparable with those for 99mTc-HMPAO-labeled mixed white blood cells, with an effective dose of 0.011 mSv/MBq. CONCLUSION: 99mTc-HMPAO-labeled monocytes have biodistribution and radiation dosimetry similar to those of 99mTc-HMPAO-labeled mixed white blood cells and might therefore be used for in vivo monitoring of immunomodulating therapy in patients with RA.     

Biodistribution and radiation dosimetry of the dopamine transporter ligand.

18F-labeled 2 beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(-2-fluoroethyl)nortropane ([18F]FECNT) is a recently developed dopamine transporter ligand with potential applications in patients with Parkinson's disease and cocaine addiction. METHODS: Estimates of the effective dose equivalent and doses for specific organs were made using biodistribution data from 16 Sprague-Dawley rats and nine rhesus monkeys. PET images from two rhesus monkeys were used to calculate the residence time for the basal ganglia. The computer program MIRDOSE3 was used to calculate the dosimetry according to the methodology recommended by MIRD. RESULTS: The basal ganglia were the targeted tissues receiving the highest dose, 0.11 mGy/MBq (0.39 rad/mCi). The effective dose equivalent was 0.018 mSv/MBq (0.065 rem/mCi), and the effective dose was 0.016 mSv/MBq (0.058 rem/mCi). CONCLUSION: Our data show that a 185-MBq (5-mCi) injection of [18F]FECNT leads to an estimated effective dose of 3 mSv (0.3 rem) and an estimated dose to the target organ or tissue of 19.4 mGy (1.93 rad).     

Biodistribution and radiation dosimetry of [N-methyl-11C]mirtazapine, an antidepressant affecting adrenoceptors.

Central adrenoceptors cannot currently be studied by PET neuroimaging due to a lack of appropriate radioligands. The fast-acting antidepressant drug mirtazapine, radiolabelled for PET, may be of value for assessing central adrenoceptors, provided that the radiation dosimetry of the radioligand is acceptable. To obtain that information, serial whole-body images were made for up to 70 min following intravenous injection of 326 and 185 MBq [N-methyl-11C]mirtazapine (specific activities E.O.S. of 119 and 39G Bq/micromol, respectively) in a healthy volunteer. Ten source organs plus remaining body were considered in estimating absorbed radiation doses calculated using MIRD 3.1. The highest absorbed organ doses were found to the lungs (3.4 x 10(-2) mGy/MBq), adrenals (1.2 x 10(-2) mGy/MBq), spleen (1.2 x 10(-2) mGy/MBq), and gallbladder wall (1.1 x 10(-2) mGy/MBq). The effective dose was estimated to be 6.8 x 10(-3) mSv/MBq, which is similar to that produced by several radioligands used routinely for neuroimaging.     

Biodistribution and radiation dosimetry of the serotonin transporter ligand 11C-DASB determined from human whole-body PET.

11C-Labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) is a selective radioligand for the in vivo quantitation of serotonin transporters (SERTs) using PET. The goal of this study was to provide dosimetry estimates for 11C-DASB based on human whole-body PET. METHODS: Dynamic whole-body PET scans were acquired for 7 subjects after the injection of 669 +/- 97 MBq (18.1 +/- 2.6 mCi) of 11C-DASB. The acquisition for each subject was obtained at 14 time points for a total of 115 min after injection of the radioligand. Regions of interest were placed over compressed planar images of source organs that could be visually identified to generate time-activity curves. Radiation burden to the body was calculated from residence times of these source organs using the MIRDOSE3.1 program. RESULTS: The organs with high radiation burden included the lungs, urinary bladder wall, kidneys, gallbladder wall, heart wall, spleen, and liver. The activity peaked within 10 min after the injection of 11C-DASB for all these organs except two--the excretory organs gallbladder and urinary bladder wall, which had peak activities at 32 and 22 min, respectively. Monoexponential fitting of activity overlying the urinary bladder suggested that approximately 12% of activity was excreted via the urine. Simulations in which the urinary voiding interval was decreased from 4.8 to 0.6 h produced only modest effects on the dose to the urinary bladder wall. With a 2.4-h voiding interval, the calculated effective dose was 6.98 microGy/MBq (25.8 mrem/mCi). CONCLUSION: The estimated radiation burden of 11C-DASB is relatively modest and would allow multiple PET examinations of the same research subject per year.     

Biodistribution and radiation dosimetry of [11C]choline: a comparison between rat and human data

Purpose  

Methyl-¹¹C-choline ([¹¹C]choline) is a radiopharmaceutical used for oncological PET studies. We investigated the biodistribution and biokinetics of [¹¹C]choline and provide estimates of radiation doses in humans.     

Biodistribution and radiation dosimetry of 18F-fluoro-A-85380 in healthy volunteers.

This study reports on the biodistribution and radiation dosimetry of 2-(18)F-Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ((18)F-fluoro-A-85380), a promising radioligand for the imaging of central nicotinic acetylcholine receptors (nAChRs). METHODS: Whole-body scans were performed in 3 healthy male volunteers up to 2 h after intravenous injection of 137-238 MBq (18)F-fluoro-A-85380. Transmission scans (3 min per step, 8 or 9 steps according to the height of the subject) in 2-dimensional mode were used for subsequent correction of attenuation of emission scans. Emission scans (1 min per step) were acquired over 2 h. Venous blood samples were taken up to 2 h after injection of the radiotracer. Urine was freely collected up to 2 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, intestine, stomach, bladder, kidneys, and liver were fitted to a monoexponential model, as an uptake phase followed by a monoexponential washout, or to a biexponential model to generate time-activity curves. Using the MIRD method, ten source organs were considered in estimating radiation absorbed doses for organs of the body. RESULTS: Injection of (18)F-fluoro-A-85380 was clinically well tolerated and blood and urine pharmacologic parameters did not change significantly. The primary routes of clearance were renal and intestinal. Ten minutes after injection, high activities were observed in the bladder, kidneys, and liver. Slow uptake was seen in the brain. The liver received the highest absorbed dose. The average effective dose of (18)F-fluoro-A-85380 was estimated to be 0.0194 mSv/MBq. CONCLUSION: The amount of (18)F-fluoro-A-85380 required for adequate nAChR imaging results in an acceptable effective dose equivalent to the patient.     

Biodistribution and radiation dosimetry of the dopamine D2 ligand 11C-raclopride determined from human whole-body PET.

Whole-body radiation dosimetry of 11C-raclopride was performed in healthy human volunteers. METHODS: Subjects (n = 6) were scanned with PET. Subjects received single-bolus injections of 11C-raclopride (S-(-)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl)]methyl-2-hydroxy-6-methoxybenzamide) (533 +/- 104 MBq) and were scanned for approximately 110 min with a 2-dimensional whole-body protocol. Regions of interest were placed over all visually identifiable organs and time-activity curves were generated. Residence times were computed as the area under the curve of the time-activity curves, normalized to injected activities and standard values of organ volumes. Absorbed doses were computed according to the MIRD schema with MIRDOSE3.1 software. RESULTS: Organs with the highest radiation burden were gallbladder wall, small intestine, liver, and urinary bladder wall. CONCLUSION: On the basis of the estimated absorbed dose, the maximum allowable single study dose under U.S. federal regulations for studies performed under Radiation Drug Research Committee is 1.58 GBq (42.8 mCi). This is still considerably higher than the doses of 11C-raclopride commonly used in research PET (370-555 MBq).     

Biodistribution and radiation dosimetry of [18F]F-PEB in nonhuman primates

INTRODUCTION: The metabotropic glutamate receptor subtype 5 (mGluR5) is distributed throughout the central nervous system (CNS), and has been suggested to be a potential target for several CNS disorders suchas Parkinson's disease, pain, anxiety, depression, schizophrenia, and addiction. We report here on the rhesus monkey biodistribution and radiation dosimetry of [F]3-fluoro-5-[(pyridine-3-yl)ethynyl]benzonitrile, [F]F-PEB, a mGluR5 positron emission tomography (PET) radiotracer. METHODS: Three male and two female rhesus monkeys were imaged using the Discovery ST PET/computed tomography scanner. A total of 25 whole body PET emissions were acquired over 3 h (23 emissions in one subject). Regions of interest were drawn in the brain, lungs, heart, liver, spleen, bladder, and testes. The absorbed radiation dose was calculated using OLINDA v1. RESULTS: At the end of the imaging session, 45% of the [F]F-PEB activity had been excreted by the liver and into the gastrointestinal tract and 10% had been excreted into the urinary bladder. When extrapolating to the adult human, the largest absorbed radiation doses were located in the upper large intestine (males: 0.18 mGy/MBq, females: 0.20 mGy/MBq) and small intestine (males: 0.16 mGy/MBq, females: 0.19 mGy/MBq). Effective radiation dose was 0.033 mSv/MBq for males and 0.034 mSv/MBq for females, similar to many other [F] ligands. CONCLUSION: The effective radiation dose of [F]F-PEB obtained from rhesus is similar to many other clinically utilized [F] ligands.     

Biodistribution and radiation dosimetry of stabilized 99mTc-exametazine-labeled leukocytes in normal subjects.

Labeling leukocytes with 99mTc-exametazime is a validated technique for imaging infection and inflammation. A new radiolabeling technique has recently been described that enables leukocyte labeling with a more stable form of 99mTc-exametazime. A normal value study of stabilized 99mTc-exametazime-labeled leukocytes has been performed, including biodistribution and dosimetry estimates in normal subjects. METHODS: Ten volunteers were injected with stabilized 99mTc-exametazime-labeled autologous leukocytes to study labeled leukocyte kinetics and dosimetry in normal subjects. Serial whole-body imaging and blood sampling were performed up to 24 h after injection. Cell-labeling efficiency and in vivo viability, organ dosimetry, and clearance calculations were obtained from the blood samples and imaging data as well as urine and stool collection up to 36 h after injection. RESULTS: Cell-labeling efficiency of 87.5% +/- 5.1% was achieved, which is similar to or better than that reported with the standard preparation of 99mTc-exametazime. In vivo stability of the radiolabeled leukocytes was also similar to in vitro results with stabilized 99mTc-exametazime and better than previously reported in vivo stability for nonstabilized 99mTc-exametazime-labeled leukocytes. Organ dosimetry and radiation absorbed doses were similar with a whole-body absorbed dose of 1.3 x 10(-3) mGy/ MBq. Urinary and fecal excretion of activity was minimal, and visual assessment of the images showed little renal parenchymal activity and no bowel activity up to 2 h after injection. CONCLUSION: Cell labeling and in vivo stability appear improved compared with the leukocytes labeled with the nonstabilized preparation of 99mTc-exametazime. There are advantages in more cost-effective preparation of the stabilized 99mTc-exametazime and an extended window for clinical usage, with good visualization of abdominal structures on early images. No significant increase in specific organ and whole-body dosimetry estimates was noted compared with previous estimates using nonstabilized 99mTc-exametazime-labeled leukocytes.     

Biodistribution, radiation dosimetry and pharmacokinetics of 111In-antimyosin in idiopathic inflammatory myopathies.

In view of the established role of 111In-antimyosin in the detection of heart muscle pathology, radiation dose estimates were made for this substance. Biodistribution and biokinetic data were obtained from our studies, which failed to show abnormal uptake of 111In-antimyosin in localized sites of skeletal muscle involvement in patients with idiopathic inflammatory myopathies. METHODS: After intravenous administration of 74 MBq (2 mCi) 111In-antimyosin, gamma camera scintigraphy was performed in 12 adult patients with inflammatory muscle disease and in 2 control patients. Six whole-body scans were performed over 72 h, and uptake of 111In-antimyosin in organs was quantified using an attenuation-corrected conjugate counting method. Residence times in source organs were used with MIRDOSE software to obtain radiation dose estimates. Pharmacokinetic parameters were derived from serial whole-blood and plasma 111In concentrations. RESULTS: The tracer cleared slowly from the circulation, and highest organ uptakes were found in the marrow and liver; kidneys showed the highest concentrations. Uptake was also evident in spleen, the facial image and male genitalia. CONCLUSION: For a typical administered activity of 74 MBq 111In-antimyosin, the kidneys receive the highest dose (58 mSv), and the effective dose is 11 mSv. Radioactivity was cleared from plasma at an average rate of 136 mL/h, and the mean steady-state distribution was approximately 5 L plasma.     

Biodistribution and dosimetry of 99mTc-BTAP-annexin-V in humans

The purpose of this study was to determine the biodistribution and the associated radiation dose of technetium-99m 4,5-bis(thioacetamido)pentanoyl-annexin-V (^99mTc-Apomate), a tracer proposed for the study of apoptosis. Eight patients (including two females) with normal kidney and liver functions were included in the study. An activity of 580ᇮ MBq of ^99mTc-Apomate was injected intravenously, immediately followed by a dynamic study of 30 frames of 1 min each. At about 1 h, 4 h and 20 h p.i., whole-body scans were acquired. All activity distributions were measured using a dual-head gamma camera. Before injection of activity, a transmission scan with a cobalt-57 flood source had been performed to determine patient attenuation. Blood samples were taken every 10 min during the first hour after injection, and at about 4 and 20 h. Urine and faeces were collected during the first 20 h. Organ uptake was estimated after correction for body background activity, attenuation and scatter. Residence times were calculated from the dynamic and whole-body studies and used as input in the Mirdose 3.1 program to obtain organ doses and effective dose. It was found that radioactivity strongly accumulated in the kidneys and the liver [at 70 min p.i., 28%NJ% and 20%dž% of the injected dose (ID), respectively]. Uptake in the target tissues (lymphomas or heart) was negligible from a dosimetric point of view. Extrapolating data from the first 20 h, one finds that approximately 73% of the ID will be excreted in the urine, and 27% in the faeces. The biological half-life of the activity in the total body was 16lj h. Some organ doses - standard deviation (SD) in µGy/MBq were: kidneys 63ᆪ, urinary bladder 20Lj, spleen 15Dž, liver 13Dž, upper large intestine 12Lj, lower large intestine 8dž, testes 6DŽ and red bone marrow 4ǂ.7. The effective dose was 7.6ǂ.5 µSv/MBq, corresponding to a total effective dose of 4.6ǂ.3 mSv for a nominal injected activity of 600 MBq. In conclusion, ^99mTc-Apomate has a high uptake in the kidneys and liver - in fact a factor of 1.3-1.6 higher than that found for the previously studied ^99mTc-(n-1-imino-4-mercaptobutyl)-annexin-V. The biological half-life is shorter, however, but still long compared with the physical half-life of ^99mTc. The faster appearance of activity in the intestines may preclude imaging of apoptosis in the abdomen. The effective dose is within the lower range of values reported for typical ^99mTc compounds.     

Biodistribution and dosimetry of 99mTc-BTAP-annexin-V in humans

The purpose of this study was to determine the biodistribution and the associated radiation dose of technetium-99m 4,5-bis(thioacetamido)pentanoyl-annexin-V (99mTc-Apomate), a tracer proposed for the study of apoptosis. Eight patients (including two females) with normal kidney and liver functions were included in the study. An activity of 580 +/- 90 MBq of 99mTc-Apomate was injected intravenously, immediately followed by a dynamic study of 30 frames of 1 min each. At about 1 h, 4 h and 20 h p.i., whole-body scans were acquired. All activity distributions were measured using a dual-head gamma camera. Before injection of activity, a transmission scan with a cobalt-57 flood source had been performed to determine patient attenuation. Blood samples were taken every 10 min during the first hour after injection, and at about 4 and 20 h. Urine and faeces were collected during the first 20 h. Organ uptake was estimated after correction for body background activity, attenuation and scatter. Residence times were calculated from the dynamic and whole-body studies and used as input in the Mirdose 3.1 program to obtain organ doses and effective dose. It was found that radioactivity strongly accumulated in the kidneys and the liver [at 70 min p.i., 28% +/- 8% and 20% +/- 4% of the injected dose (ID), respectively]. Uptake in the target tissues (lymphomas or heart) was negligible from a dosimetric point of view. Extrapolating data from the first 20 h, one finds that approximately 73% of the ID will be excreted in the urine, and 27% in the faeces. The biological half-life of the activity in the total body was 16 +/- 7 h. Some organ doses +/- standard deviation (SD) in microGy/MBq were: kidneys 63 +/- 22, urinary bladder 20 +/- 6, spleen 15 +/- 3, liver 13 +/- 3, upper large intestine 12 +/- 6, lower large intestine 8 +/- 4, testes 6 +/- 2 and red bone marrow 4 +/- 0.7. The effective dose was 7.6 +/- 0.5 microSv/MBq, corresponding to a total effective dose of 4.6 +/- 0.3 mSv for a nominal injected activity of 600 MBq. In conclusion, 99mTc-Apomate has a high uptake in the kidneys and liver--in fact a factor of 1.3-1.6 higher than that found for the previously studied 99mTc-(n-1-imino-4-mercaptobutyl)-annexin-V. The biological half-life is shorter, however, but still long compared with the physical half-life of 99mTc. The faster appearance of activity in the intestines may preclude imaging of apoptosis in the abdomen. The effective dose is within the lower range of values reported for typical 99mTc compounds.     

Biodistribution and radiation dosimetry of the synthetic nonmetabolized amino acid analogue anti-18F-FACBC in humans.

The synthetic leucine amino acid analog anti-1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid (anti-(18)F-FACBC) is a recently developed ligand that permits the evaluation of the L-amino acid transport system. This study evaluated the whole-body radiation burden of anti-(18)F-FACBC in humans. METHODS: Serial whole-body PET/CT scans of 6 healthy volunteers (3 male and 3 female) were acquired for 2 h after a bolus injection of anti-(18)F-FACBC (366 +/- 51 MBq). Organ-specific time-activity curves were extracted from the reconstructed data and integrated to evaluate the individual organ residence times. A uniform activity distribution was assumed in the body organs with urine collection after the study. Estimates of radiation burden to the human body were calculated on the basis of the recommendations of the MIRD committee. The updated dynamic bladder model was used to calculate dose to the bladder wall. RESULTS: All volunteers showed initially high uptake in the pancreas and liver, followed by rapid clearance. Skeletal muscle and bone marrow showed lower and prolonged uptake, with clearance dominated by the tracer half-life. The liver was the critical organ, with a mean absorbed dose of 52.2 microGy/MBq. The estimated effective dose was 14.1 microSv/MBq, representing less than 20% of the dose limit recommended by the Radioactive Drug Research Committee for a 370-MBq injection. Bladder excretion was low and initially observed 6 min after injection, well after peak tracer uptake in the body organs. CONCLUSION: The PET whole-body dosimetry estimates indicate that an approximately 370-MBq injection of anti-(18)F-FACBC yields good imaging and acceptable dosimetry. The nonmetabolized nature of this tracer is favorable for extraction of relevant physiologic parameters from kinetic models.     

Biodistribution and radiation dosimetry of radioiodinated-SCH 23982, a potential dopamine D-1 receptor imaging agent

Radioiodinated-SCH 23982 is a potential agent for the imaging of dopamine D-1 receptors in the human brain. In vivo binding of [125I]SCH 23982 to D-1 receptors in rat brain was determined over 4 hr. The ratio of activity in striatum and frontal cortex to that in cerebellum increased over the first 2 hr to maximum values of 4.4:1 and 2.1:1, respectively. The percent injected dose in whole brain at 0.5 and 2 hr were 0.62 and 0.15, respectively. Administration of the antagonists propranolol (beta-1), prazosin (alpha-1), haloperidol (D-2) and ketanserin (5HT-2) did not significantly alter the striatum/cerebellum ratio; however, SCH 23390, a D-1 antagonist, totally blocked ligand uptake by striatum and frontal cortex. Biologic distribution data in the rat were determined after injection of 3 microCi of [125I]SCH 23982. 76% of the injected dose was excreted in 48 hr via the liver and kidneys. Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads and red bone marrow were calculated for humans using the physical decay data for 123I. The critical organ was found to be the lower large intestine which received 1.1 rad/mCi of the administered dose. The total-body dose was 63 mrad/mCi. The data indicate that [123I]SCH 23982 should be a suitable agent for imaging the D-1 dopamine receptor in the human brain by single photon emission computed tomography.