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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 dosesor = 5.29 MBq/kg and 5 +/- 3 days with dosesor = 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.

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.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.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 (p0.05) 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 [p0.01]); (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.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.

Biokinetics and imaging characteristics of 117mSn(4+)DTPA have been studied in patients with metastatic bone pain.Seventeen patients with bone pain due to metastasis were given three dose levels: 180 microCi/kg (6.66 MBq/kg), 229 microCi/kg (8.47 MBq/kg) and 285 microCi/kg (10.55 MBq/kg) body weight. Periodic blood and daily urine samples were collected for 14 days to measure percent injected activity retained in blood and that excreted in urine. Simultaneous anterior and posterior view whole-body images were obtained under identical scan settings at 1, 3.5 and 24 hr and on Days 3 and 7 and between 4-6 and 8-10 wk postinjection. The total body retention was calculated using the geometric mean counts.After intravenous injection, the total body clearance of 117mSn(4+)DTPA shows two components: a soft-tissue component and a bone component. The soft-tissue component accounts for 22.4% of the dose and consists of four subcomponents with an average biologic clearance half-time of 1.45 days (range 0.1-3.2 days). The bone component accounting for the remaining 77.6% of the dose shows no biologic clearance. A mean 22.4% of the dose is excreted in urine in 14 days; 11.4% within 24 hr. The uptake pattern appears similar to that of 99mTc-MDP. Peak uptake is observed in normal bone by 24 hr and metastatic lesions by 3-7 days. Pain palliation was observed with all three doses levels.Among the four potential bone pain palliation radionuclides, 117mSn(4+)DTPA demonstrates the highest bone uptake and retention. Some biokinetic and radionuclidic features of 117mSn(4+)DTPA are similar to other agents, but many features are different and unique and may make it an ideal bone pain palliation agent. Double-blind comparative studies are needed to determine its exact role in bone pain palliation.

Bone seeking radiopharmaceuticals consist of diagnostic (primarily single photon emitters) and therapeutic agents. The therapeutic radiopharmaceuticals are utilized on the basis of their particulate emissions (primarily beta-) and thus are treated differently than the single photon bone imaging agents. Lately, the therapeutic bone seekers have attained increasing importance due to their potential role in alleviating pain from osseous metastases in cancer patients. However, there seems to be a paucity of published data on the pharmacokinetics of most of these agents. This paper will briefly review and summarize the presently available pharmacokinetic information on the various therapeutic bone seeking radiopharmaceuticals. Bone imaging agents based on single photon emitters will not be covered since they have been extensively discussed in the published literature.

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.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.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.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.

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.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.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.These values will agree with previous estimates and indicate an excellent safety margin.

The physical and biological attributes of 117mSn(4+)-DTPA indicate that it should be an effective agent for palliative therapy of painful bony metastatic disease. The aim of this study was to evaluate whether or not this agent could effectively reduce pain while sparing the hemopoietic marrow from adverse effects.Fifteen patients (10 males and 5 females) with painful bony metastases from various primary cancers were included in the study. Seven patients received 1.22 to 3.11 MBq/kg of 117mSn intravenously (Group 1) and eight patients received 4.85 to 5.77 MBq/kg (Group 2). All but one were treated as outpatients and followed for a minimum of 2 mo.In the first group, pain relief was non-assessable in four patients because of death or additional treatment of soft-tissue disease by another modality. One patient had no relief of pain, one had complete relief of pain and one had transient relief of pain. No myelotoxicity was observed. For Group 2, three patients achieved complete relief of pain, two good relief, two partial relief and one began to experience pain relief when he suffered a pathological fracture 2 mo post-treatment. None of these patients had myelotoxicity.Tin-117m(4+)-DTPA can reduce pain from metastatic disease to bone without inducing adverse reactions related to bone marrow. Further studies are needed to assess tolerance levels for the bone marrow and to evaluate response rates and duration of effect.

The uptake, distribution, and clearance properties of 123I-IMP in the brain were evaluated in controls and asymptomatic crack users to investigate cerebral blood flow alterations in crack abuse. Serial dynamic planar images of the brain (0-25 min), SPECT of the brain (0.5 hr and 4 hr) and whole-body scans (75 min) were obtained in 21 crack abusers and 21 control subjects. Major observations include: (a) foci of abnormally reduced 123I-IMP activity mainly in the frontal and parieto-occipital cortex or marked irregularities in the uptake of 123I-IMP throughout the cerebral cortex consistent with moderate to severe disruption in regional cerebral blood flow were observed on the 0.5 hr SPECT images of 16/21 asymptomatic crack users; (b) no correlation could be demonstrated between the incidence or severity of SPECT perfusion abnormality with the frequency, amount or length of time of crack use; (c) focal perfusion defects observed in 6/21 crack users on the 0.5-hr SPECT images partially or completely filled-in on delayed SPECT at 4 hr in four of six subjects; (d) the rate of cerebral uptake of 123I-IMP in crack users averaged 23% less than observed in control subjects over the first 25 min after tracer administration; and (e) 123I-IMP activity reaching the brain of cigarette smoking control subjects (n = 14) at 25 min after injection averaged 42.5% less than in nonsmoking controls (n = 7). Quantitative measurements of the uptake and distribution properties of 123I-IMP in the brain proved to be an objective, sensitive and useful measure of regional cerebral blood flow in crack abuse.

201Tl-chloride and 204Tl-nitrate were similarly distributed in organs of mice 10 min and 60 min after intravenous injection. Autoradiographic studies were carried out with 204Tl-nitrate in rats (injected intraperitoneally) as well as in mice and dogs (injected intravenously). Thallium localized in the cells of proximal and distal convoluted tubules and collecting tubules of the kidney. In the intestines, it was distributed mostly in the cells of the smooth musculature and surface epithelium of the villi. Some silver grains were seen in the goblet cells and in the lumen as well. It localized in the sarcoplasm of the myocardium and the skeletal muscle cells. In thyroid, most of the thallium was seen in the colloidal part of the follicle. In testes, silver grains were seen in and around the cells of Sertoli and in the lumen of the seminiferous tubules. Some localized concentration in the interstitial cells of the testes was also observed.

The in vivo measurements of 127Xe and 79Kr clearance from the whole body indicate five components, with biologic half-times ranging from 13 sec to 17.04 h. The slowest component correlated highly with percent total-body fat, the half-time varying between 7.59 and 17.04 for xenon and between 4.20 and 9.62 h for krypton. The long-term retention was localized to regions of high fat content as determined by the coincidence mode of the whole-body counter and images obtained with the scintillation camera. The estimated dose based on the retention data of this study would indicate increased doses to body fat and gonads as compared with those previously calculated. These increased doses are due to the longer retention of noble gases in fat. After 10-min inhalations of a mixture of 127Xe and air and 79Kr and air, approximately one third of the total 127Xe and one fifth of the total 79Kr were transferred to the body tissues, extrapolated back to the start of gas washout. Of this amount, approximately 13% of the 127Xe and approximately 9% of the 79Kr were associated with the slowest component.

Nonvisualization of the gallbladder is the primary finding in cholescintigraphy for acute cholecystitis. Recent investigators have described a useful secondary finding of increased pericholecystic hepatic activity (PCHA). A case of acute cholecystitis is presented in which the PCHA was round in configuration and appeared in the first 5 minutes of the study. This may be a source of diagnostic error if it is interpreted as visualization of the normal gallbladder. Appearance of the PCHA has not been previously described before 30 minutes. This case of early appearance raises the possibility that hyperemia may play a role as the cause in some forms of the PCHA. The phantom gallbladder was correctly identified as PCHA by observing the peak of activity of the PCHA occurring before the appearance of intrahepatic biliary radicals.

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.

The concentration of radioactive phosphorus in uveal melanoma and normal parts of the eye was determined in vitro in 14 eyes. The eyes were enucleated after a positive 32P uptake test. Portions of the melanoma as well as normal choroid, retina, sclera, lens, and vitreous were analyzed. The 32P uptake test had been performed at various intervals after intravenous administration of 32P from 24 to 556 hr. The in vitro uptake of 32P was compared to cell type, tumor volume, time of testing, percent uptake measured clinically, and specific activity. The only positive correlation was between percent uptake measured clinically and 32P concentration (dpm/gm). A higher concentration of phosphorus in melanoma resulted when carrier-free 32P was used. A negative correlation existed between number of hours from injection to clinical measurement of percent uptake, although melanoma to normal choroid ratios did not change from 24 to 72 hr. No correlation was found between uptake and tumor volume. The sample was small; however, we saw no correlation between 32P uptake and degree of malignancy.

To test the hypothesis that regional left ventricular filling reflects diastolic changes in contiguous areas of myocardium, we performed radionuclide ventriculograms on normal subjects, patients with left anterior descending coronary artery disease, and patients with anteroseptal myocardial infarctions. We reasoned that because diastolic properties of the anteroseptal myocardium should be different in the three groups of patients, regional filling in the anteroseptal area of the left ventricle should also be different, if regional filling does, indeed, reflect diastolic changes in the adjacent myocardium. While anteroseptal regional filling in the normal subjects was different than regional filling in the two patient groups, the degree of filling abnormality was similar in patients with and without myocardial infarctions. Our results suggest that regional left ventricular filling is not exclusively determined by diastolic changes in contiguous areas of myocardium.

After intravenous injection, 11C-octylamine - HC1 is rapidly sequestered by the rabbit lung. The initial lung uptake during the first minute was 70 +/- 6% of the administered dose, and 40% of the injected dose remained after 15 min. Approximately 12% of the administered radioactivity is exhaled as 11CO2 during the first 30 min.

In patients with gliomas who were stable or improving, we noted a disparity between clinical status and computed tomography (CT) brain scan results. To elucidate this finding, 29 patients were sequentially scanned with 2.0 mCi of 201Tl (5-30 min), 20 mCi [99mTc]gluceptate (GH) (3-4 hr) and 7-10 mCi 67Ga (48-72 hr). A total of 198 images were obtained. A set of three scans at a midpoint in follow up was selected for analysis. Seven patients who died had neuropathologic data available; brain sections were reconstructed to match radionuclide views without knowledge of image results. In the seven patients with autopsy data, 201Tl offered the most accurate correlation with viable tumor. Gallium-67 gave similar results in patients not receiving steroids. Technetium-99m GH scans could not allow differentiation between tumor, necrosis, and edema. Similarly, the CT scan could not routinely differentiate between fibrotic, nonfibrotic, necrotic, and neoplastic tissue. In the 22 patients without autopsy data, 201Tl scans commonly showed smaller and more focal abnormal uptake when compared with [99mTc]GH and 67Ga scans. Thallium-201 scans more accurately reflect viable tumor burden than other radionuclide studies of primary brain tumors, are minimally affected by concomitant steroid administration, can be performed immediately following tracer administration, and complement the anatomic data obtained from CT scans.

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.

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.