Erythropoietic and reticuloendothelial function in bone marrow in dogs.

Erythropoietic and reticuloendothelial functions in bone marrow were found to be identically distributed between various bones and within individual bones in the dog.

Melanin content of hamster tissues, human tissues, and various melanomas.

Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented "background" tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to 30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma.

Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver and 100 for "back-ground" tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 microgram CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the 10B(n, alpha)7Li reaction.

Global and regional left ventricular ejection fraction abnormalities during exercise in patients with silent myocardial ischemia.

Sixteen asymptomatic patients with coronary artery disease and silent myocardial ischemia were studied with exercise radionuclide ventriculography. Radionuclide ventriculograms were analyzed for changes in ejection fraction globally and in three regions. Results were compared with radionuclide ventriculograms in 24 symptomatic patients. Both groups (silent myocardial ischemia and angina) were similar in prevalence of multivessel disease and previous myocardial infarction, as well as in age and sex. Global ejection fraction decreased by 0.06 in both groups during exercise; regional ejection fraction also decreased by similar amounts in the two groups. Furthermore, the percent of regions with normal ejection fraction at rest that demonstrated a decrease during exercise was identical: 19 (60%) of 33 versus 26 (60%) of 46. These exercise radionuclide ventriculographic results suggest that abnormalities in regional and global left ventricular wall motion are similar in patients with coronary artery disease with and without silent myocardial ischemia.

Treatment of metastatic bone pain with tin-117m Stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study.

The physical characteristics of Sn-117m combined with the biodistribution of the compound tin-117m (Stannic, 4+) diethylenetriaminepentaacetic acid (Sn-117m DTPA) suggest that it should be an excellent agent for the palliation of pain from bony metastases. Prior work has established the dosimetry and the safety for the material in human beings. The presence of low-energy conversion electrons should result in the relative sparing of the bone marrow while delivering a high radiation dose to sites of bony metastatic disease. Forty-seven patients with painful bone metastases from various malignancies were treated with Sn-117m DTPA. The patients were assigned to five different dose levels ranging from 2.64 to 10.58 MBq (71-286 microCi) per kg of body weight. Follow-up included review of pain diaries, performance scores, analgesic requirements, blood chemistries, and hematological assessment. Three patients received a second treatment. There was an overall response rate for relief of pain of 75% (range, 60-83%) in the 40 treatments that could be evaluated. No correlation was apparent in this limited series between response rate and the five dose levels used. The relief was complete in 12 patients (30%). The time to onset of pain relief was 19 +/- 15 days with doses < or = 5.29 MBq/kg and 5 +/- 3 days with doses > or = 6.61 MBq/kg. Myelotoxicity was minimal, with only one patient having a marginal grade 3 WBC toxicity. On the basis of our data, Sn-117m DTPA should be an effective and safe radiopharmaceutical for palliation of painful bony metastases. A large-scale trial is warranted to evaluate it in comparison to other similar agents.

Radiopharmaceuticals. 16. Halogenated dopamine analogs. Synthesis and radiolabeling of 6-iododopamine and tissue distribution studies in animals.

A simple halogenated derivative of dopamine, 6-iododopamine (1), has been synthesized using two different methods. These synthetic sequences have been applied to the radiolabeling of 1 with carbon-11, iodine-131, and iodine-123. The tissue distribution of 1 in mice, dogs, and rats was determined. The ratio of radioactivity (%/g) in the adrenal medulla-kidney in dogs increases from 3.45 at 2 h postinjection to 33.3 at 24 h postinjection. Thyroid uptakes in mice, dogs, and rats show that in vivo deiodination of 1 is not significant.

Growth-hormone and somatostatin effects on [75Se]selenomethionine uptake by the pancreas.

The imaging of the pancreas with [75Se]selenomethionine has a low rate of reliability. This study was carried out in order to elucidate some factors that may be important in affecting the degree of uptake of the tracer by the pancreas. Studies were carried out in animals to observe the effects of growth-hormone (GH), somotostatin (SRIF), L-DOPA, and apomorphine administration on the distribution of [75Se]selenomethionine. Intravenously administered GH significantly depressed pancreatic uptake of Se-75 in mice and dogs and depressed the pancreas-to-liver concentration ratio (P/L). The effect of i.p. GH in mice was to decrease the P/L ratio, but the decrease in pancreatic uptake was not statistically significant. There was also a greater effect of GH in dogs than in mice, with pancreatic uptake decreasing from 5.60 +/- 2.17% to 1.24 +/- 0.96% and the P/L from 4.78 +/- 1.85 to 0.97 +/- 0.73. L-DOPA and apomorphine produced effects similar to GH in mice. SRIF in small doses had little effect, but in larger doses it enhanced pancreatic uptake, although not affecting P/L. The results indicate that hypothalamic factors may be important in affecting the function of the exocrine pancreas. Both L-DOPA and apomorphine are known to stimulate GH production through hypothalamic-pituitary pathways. In addition to suppressing GH release, SRIF may have direct effects on the exocrine pancreas.

Radiation exposure to human trachea from xenon-133 procedures.

UNLABELLED: The general dosimetry of 133Xe for human studies is well documented, but the resultant radiation exposure to tracheal tissue is poorly known. This organ is of central relevance because the tracer is primarily eliminated through exhalation. METHODS: We report actual 133Xe concentrations in respiratory air during measurement of regional cerebral blood flow (rCBF), when the tracer is administered both by inhalation and intravenous injection. Data were collected from 102 patients, with equal gender representation and an age range of 18-82 yr. Most of the patients had subarachnoid hemorrhage or Alzheimer's disease or were normal control subjects. Average administered doses were 18 +/- 4 mCi by inhalation and 15 +/- 3 intravenously. RESULTS: We found average respiratory concentrations of about 1.80 mCi/liter during a 1-min inhalation and 0.74 mCi/liter following intravenous injection of standard doses. These activities drop rapidly: average respiratory concentrations during the second minute are 0.70 mCi/liter for inhalation and 0.19 mCi/liter for intravenous injection and reach negligible levels thereafter. We calculate that the tracheal absorbed dose from 133Xe procedures is approximately 28 mrad following inhalation and about 11 mrad following intravenous injection. These values reflect the full 11-min exposure, but most of the activity is only present initially. CONCLUSION: These values will agree with previous estimates and indicate an excellent safety margin.

The effects of deferoxamine mesylate on gallium-67 distribution in normal and abscess-bearing animals: concise communication.

Deferoxamine mesylate (DFO), given to rabbits 20 min after gallium-67 citrate, induces prompt and rapid urinary excretion of Ga-67 activity with concommitant decrease in blood and muscle activity. When DFO is given after 2 hr or later, the effect is smaller (15% decrease in blood activity compared with 50%). In abscess-bearing rats the same effect was observed: DFO accelerated the Ga-67 blood clearance by increasing urinary excretion. Tissue-distribution studies and direct counting of abscesses showed that DFO lowers Ga-67 activity in all organs as well as in the abscess if given 2 or 4 hr after Ga-67 citrate, but the abscess-to-blood ratio increases. At 24 hr after Ga-67 citrate, DFO administration causes an improvement in the ratios of abscess-to-blood and abscess-to-normal tissue. Thus, DFO could be used to decrease the radiation burden from Ga-67 citrate after imaging has been performed, and also to increase the target-to-nontarget ratio.

Whole-body retention of radioxenon.

The total-body retention of 127Xe, and its variation with time following short, nonequilibrium periods of inhalation, were measured in vivo so as to refine dosimetry calculations. Radioactivity in the chest region and in the recirculating xenon-air mixture was measured continuously during re-breathing of the gas mixture and in the first 5 min of the immediate gas-washout period using a scintillation camera and shielded NaI detector, respectively. Subjects were then counted in a whole-body counter at varying time intervals until background levels were reached, usually in 72 hr. Five components of Xe clearance from the entire body were measured; they had biologic half-times of 21.7+/-12.4 sec, 3.05+/-1.72 min, 0.04+/-0.11 hr, and 2.71+/-0.87 hr, and a long-term component varied between 7.59 and 17.04 hr. The half-time of the last component correlated highly with the percent of total-body fat. After 10-min inhalations of the xenon-air mixture, approximately one-third of the total xenon was transferred to the body tissues, extrapolated back to the start of gas washout. Of this amount, 13% was associated with the slowest component of clearance.

MIRD Pamphlet No. 15: Radionuclide S values in a revised dosimetric model of the adult head and brain. Medical Internal Radiation Dose.

UNLABELLED: Current dosimetric models of the brain and head lack the anatomic detail needed to provide the physical data necessary for suborgan brain dosimetry. During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head for use in estimating regional absorbed dose within the brain and its adjacent structures. METHODS: A new brain model has been developed that includes eight subregions: the caudate nuclei, the cerebellum, the cerebral cortex, the lateral ventricles, the lentiform nuclei, the thalami, the third ventricle and the white matter. This brain model is incorporated within a total revision of the head model presented in MIRD Pamphlet No. 5 Revised. Modifications include the addition of the eyes, the teeth, the mandible, an upper facial region, a neck region and the cerebrospinal fluid within both the cranial and spinal regions. RESULTS: Absorbed fractions of energy for photon and electron sources located in 14 source regions within the new model were calculated using the EGS4 Monte Carlo radiation transport code for particles in the energy range 10 keV-4 MeV. These absorbed fractions were then used along with radionuclide decay data to generate S values for 24 radionuclides that are used in clinical or investigational studies of the brain, 12 radionuclides that localize within the cranium and spinal skeleton and 12 radionuclides that selectively localize in the thyroid gland. CONCLUSION: A substantial revision to the dosimetric model of the adult head and brain originally published in MIRD Pamphlet No. 5 Revised is presented. This revision supports suborgan brain dosimetry for a variety of radiopharmaceuticals used in neuroimaging. Dose calculations for the neuroimaging agent 1231-tropane provide an example of the new model and yield mean brain doses that are consistent with published values. However, the absorbed dose to subregions within the brain such as the caudate and lentiform nuclei may exceed the average brain dose by a factor of up to 5.

A revised dosimetric model of the adult head and brain.

UNLABELLED: During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head. Brain and head models developed in the past have comprised only simplistic representations of this anatomic region. METHODS: A new brain model has been developed which includes eight subregions: the caudate nucleus, the cerebellum, the cerebral cortex, the lateral ventricles, the lentiform nucleus, the thalamus, the third ventricle and the white matter. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. The head model, which includes both the thyroid and eyes, was modified in this work to include the cerebrospinal fluid within the cranial and spinal regions. RESULTS: Absorbed fractions of energy for photon and electron sources located in thirteen source regions within the new head model were calculated using the EGS4 Monte Carlo radiation transport code for radiations in the energy range 10 keV to 4 MeV. CONCLUSION: S-values were calculated for five radionuclides used in brain imaging (11C, 15O, 18F, 99(m)Tc and 123I) and for three radionuclides showing selective uptake in the thyroid (99(m)Tc, 123I, and 131I). S-values were calculated using 100 discrete energy points in the beta-emission spectrum of the different radionuclides.

Utility of technetium-99m-DTPA in determining regional ventilation.

UNLABELLED: The goal of this study was to determine the usefulness of radiolabeled aerosols in the assessment of regional ventilation in tracheotomized patients maintained on mechanical ventilation. METHODS: Three commercially available radioaerosol nebulizer kits were studied on the bench to determine nebulizer efficiency and particle distribution of 99mTc-DTPA aerosols. We studied ventilated tracheotomized human subjects with a gamma camera and simultaneously measured regional ventilation with 81mKr gas and 99mTc-DTPA aerosol. Images were compared by analysis of radioactivity distributions in computer-generated regions of interest. RESULTS: The UltraVent nebulizing system produced the smallest particles with a mass median aerodynamic diameter of 0.9 micron compared to the AeroTech I and Venti-Scan II systems, which both produced aerosols of 1.3 microns. Despite relatively small particle sizes, 99mTc-DTPA deposition images with the UltraVent nebulizer did not accurately represent regional ventilation as measured by 81mKr equilibrium. Visual inspection of images revealed significant amounts of particle deposition in the region of the trachea which was diminished but not eliminated following replacement of the tracheotomy tube inner cannula. Based on regional analysis, correlation between radioactivity distributions of both isotopes was poor (r = 0.262, p = 0.162) with segmental analysis suggesting that the upper and middle lung regions were significantly affected by residual tracheal activity. CONCLUSION: The lungs of patients maintained on mechanical ventilation can be imaged after the inhalation of 99mTc-DTPA from commercially available delivery kits, but the correlation between aerosol deposition and regional ventilation is poor. Better definition of ventilated lung segments is obtained when using a gas such as 81mKr because tracheal activity with the radiolabeled gas is minimized.

Thallium-201 for medical use. II: Biologic behavior.

Thallium-201 has been evaluated for myocardial imaging by determining its distribution and assessing its imaging properties. Organ distribution with time was studied in goats, chosen for their large size and easy operability. Myocardial imaging was performed in living and sacrificed goats and also in two anesthetized dogs, without infarction. Infarcts were made by ligature at open chest surgery on the goats and the infarcts subsequently confirmed histologically. The myocardium of normal and infarced, young and old goats was cut into blocks and the isotope distribution measured and compared with that in the lungs, liver, spleen, and kidney in normal goats. The renal medulla-to-cortex concentration ratio in goats was studied and is approximately five. The heart uptake exceeds 3% for 100 min whereas contiguous organs have less than one-half of the myocardial concentration, and blood clearance is rapid. One problem may prove to be inhomogeneity of uptake of thallium in the "normal" myocardium, showing a standard deviation of 1u% in a young goat and 29% in an old goat. In view of the good myocardial uptake, however, this work strongly suggests the trial 201Tl in patients.

A clinical comparison of Xe-127 and Xe-133 for ventilation studies.

Xenon-133 and xenon-127 were compared by performing ventilation studies with both radionuclides in 19 patients with a variety of lung diseases. Assessment of the counting rate over the chest, relative to the radioactivity in the lungs, permitted the evaluation of each isotope in terms of usable photons detected by a scintillation camera with a large field of view and appropriate collimation. A greater photon yield was obtained with Xe-127. Markedly improved resolution was shown by measurement of a line phantom, but was not apparent on subjective appraisal of scintiphotos except in the washout phase. Xenon-127 appears to be preferable to Xe-133 because of the higher counting rates, lower patient radiation dose, and longer shelf life. In addition, a prior perfusion study using a Tc-99m radiopharmaceutical does not affect the quality of a Xe-127 ventilation study. The use of Xe-127 therefore permits the selection for ventilation studies of only those patients with suspected pulmonary embolism, and eliminates unnecessary radiation exposure. A further improvement in image quality obtained with Xe-127 should be possible with certain modifications of the scintillation camera that would permit use of the 375-keV photopeak along with the 172- and 203-keV gamma energies. Charcoal traps designed for Xe-133 will require additional shielding and longer storage time when used for Xe-127. Xenon-127, however, might be used again after appropriate processing.

Detection of ocular melanoma with 4-(3-dimethylaminopropylamino)-7-[123I]-iodoquinoline.

Iodine-123-labeled 4-(3-dimethylpropylamino)-7-iodoquinoline was evaluated in nine patients. By using a specially designed dual-pinhole ocular collimator, it was possible to obtain positive images at 2-6 hr for only 70% of the cases with subsequently proven ocular melanomas.

Thallium-201 for medical use. Part 3: Human distribution and physical imaging properties.

Studies were undertaken to determine the biologic distribution of thallium-201 in man. The disappearance from the blood is extremely rapid and intracellular deposition is nearly immediate. The biologic half-time of thallium was measured by both the Brookhaven whole-body counter and the Donner whole-body scanner, with excellent agreement. The effective whole-body half-time of thallium-201 is about 57 hr. Concentration of activity was seen in the heart, kidneys, large bowel, and thyroid. The whole-body radiation dose is 0.21 rads/mCi.

Impaired permeability in radiation-induced lung injury detected by technetium-99m-DTPA lung clearance.

UNLABELLED: This study evaluates the use of the 99mTc-DTPA aerosol lung clearance method to investigate radiation-induced lung changes in eight patients undergoing radiotherapy for lung or breast carcinoma. The sensitivity of the method was compared with chest radiography for detecting radiation-induced changes in the lung, regional alterations within (irradiated region) and outside (shielded region) the treatment ports, effect of irradiated lung volume, and dependence on time after radiotherapy. METHODS: Serial DTPA lung clearance studies were performed before the first radiation treatment (baseline), then weekly during a 5- to 7-wk course, and up to 12 times post-therapy over periods of 56-574 days. The total activity deposited in the lungs for each study was approximately 150 microCi (approximately 5.6 MBq). DTPA clearance, expressed in terms of the biological half-time, t 1/2, was computed from the slopes of the least-squares fit regression lines of the time-activity curves for the first 10 min for irradiated and shielded lung regions. RESULTS: Major findings include: (a) significant and early DTPA t 1/2 changes were observed in all patients during and after radiotherapy; (b) changes in DTPA t 1/2 values were observed in both irradiated and shielded lung regions in all patients suggesting a radiation-induced systemic reaction; (c) changes in DTPA t 1/2 values were correlated (p < 0.05) with the irradiated lung volumes; (d) significantly reduced DTPA t 1/2 values were observed in three patients who subsequently presented with clinical symptoms and/or radiographic changes consistent with radiation pneumonitis (t1/2 felt to 19% +/- 6% of baseline values, compared with 64% +/- 17% in the remaining patients [p < 0.01]); (e) the onset of decreased DTPA t 1/2 values in these three patients occurred 35-84 days before clinical symptoms and/or radiographic changes; and (f) DTPA t 1/2 tended to approach baseline values with time after radiotherapy, suggesting a long-term recovery in lung injury. CONCLUSION: These observations show significant and early alterations in DTPA lung clearance during and after radiotherapy that may provide a sensitive assay to monitor changes in radiation-induced lung injury and may facilitate early therapeutic intervention.

Biological distribution and excretion of DTPA labeled with Tc-99m and In-111.

For the purpose of radiation dose estimates, organ assays and excretion measurements of the Tc-99m and In-111 complexes with DTPA were conducted in dogs at various time intervals up to 24 hr, and the results compared with available human data. The peak concentration of the Tc-99m complex, at 3 min after injection, was 5% of the administered dose for one kidney, 3.5% for the liver, and 3.5% for the small bowel. No organ system except the urinary tract reached a concentration higher than that in blood for several hours after the injection. The biliary excretion of these agents was extremely low, and their elimination in the feces was negligible. In man, it appears that the residual 4-5% of an administered dose not eliminated in the urine by 24 hr is widely distributed in various tissues. The distribution of the In-111 complex is similar but not identical to that of the Tc-99m complex.

Sensitivity of Kr-81m and Xe-127 in evaluating nonembolic pulmonary disease.

The relative sensitivities of Kr-81m and Xe-127 in detecting lung ventilation defects was evaluated in 80 patients with nonembolic pulmonary diseases. Krypton-81m ventilation images (500,000 count) were interdigitated with Tc-99m MAA perfusion images; both were compared with Xe-127 images. The distributions of the two gases were also compared on the basis of point-by-point computer analyses. Xenon-127 was found to be more sensitive than Kr-81m in clinical evaluations of scintiphotos--although they were equivalent by computer analyses--in indicating regions of impaired ventilation in patients with obstructive airways disease.