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Background: We determined staff radiation dose during rest and stress rubidium 82 myocardial perfusion positron emission tomography (PET) imaging., Methods and Results: Patients received 1,587 +/- 163 MBq (42.9 +/- 4.4 mCi) Rb-82 during rest or pharmacologic stress. A pressurized ion chamber was used to monitor radiation exposure in 50 examinations. For comparison, staff exposure during pharmacologic stress in 20 other patients receiving 1,204 +/- 55.5 MBq (32.54 +/- 1.5 mCi) technetium 99m 2-methoxy isobutyl isonitrile (MIBI) was measured. For Rb-82 infusion and PET acquisition, the mean dose was 0.45 +/- 0.25 microSv (0.045 +/- 0.025 mrem). Exposure for routine stress testing at variable distances from the patient was equivalent to background. Similar exposure for pharmacologic stress testing through 7 minutes after injection of Tc-99m MIBI at variable distances was 1.075 +/- 0.32 microSv (0.108 +/- 0.03 mrem). However, exposure for stress tests starting 7 minutes after Rb-82 infusion at 0.5 m was estimated at 0.4 microSv (0.04 mrem). To determine the potential radiation dose for those responding to a medical emergency or otherwise in close proximity to a patient, we measured the mean cumulative dose at 0.5 m from 0 to 7 minutes of Rb-82 infusion, which resulted in 19.1 +/- 5.8 microSv (1.9 +/- 0.58 mrem)., Conclusions: Radiation doses for all tasks during routine Rb-82 stress-rest PET are lower than measured Tc-99m MIBI values. However, the radiation dose in close proximity to the patient during or immediately after Rb-82 infusion can be considerably higher, underscoring the need for strict attention to source distance and contact times.

The Brigham and Women's Hospital is an ~700 bed broad-scope licensed facility with a vigorous fluoroscopy service. Concomitant with this service is an equally robust quality management program to safeguard both patient and personnel from excessive radiation doses. The FDA, in an attempt to avoid serious skin injury for certain fluoroscopically guided procedures, issued a Public Health Advisory in 1994. Four years later the institutional Radiation Safety Committee voted to expand an existing fluoroscopic safety course to include a more formal credentialing/safety requirement. The specific parameters associated with this program follow.

The concentration of 111In in breast milk in a 10 weeks postpartum woman was measured at daily intervals up to 72 h post-injection of 5.3 mCi (196 MBq) of 111In-octreotide (OctreoScan). Radiation surveys were also performed at the breast surface. The disappearance of 111In from the breast milk exhibited a bi-exponential pattern with a maximum concentration of 14.2 nCi (0.54 kBq) per 125 ml feeding at 4 h, with lower values thereafter. External surveys at the breast surface also showed a bi-exponential decrease with time. The maximum reading was 8.3 mrem x h(-1) (0.83 mSv x h(-1)) immediately after administration. This rapidly decreased due to 85% urinary excretion by 24 h. Breast milk tracer content and external surveys at the breast surface were determined at 3 h intervals for up to 10 days. If a newborn is nursed for the first 10 days, the internal and external dose equivalents would be 22.97 mrem (0.23 mSv) and 27.86 mrem (0.28 mSv), respectively, for a total of 50.83 mrem (0.5 mSv). The patient was instructed to resume breast-feeding on day 10, when the newborn received a total dose equivalent of 1.55 mrem (0.016 mSv). This dosimetry is based on a very conservative assumption, whereby 100% of the ingested 111In becomes systemic and follows adult bio-behaviour. Oral indium has been shown to be poorly absorbed from the gastrointestinal tract (approximately 0.15%), which suggests the infant's dose could be considerably less. Based on this case report, mathematical relationships are presented for determining the nursing infant's dose equivalent from internal and external exposures relative to time after the maternal administration of 111In-octreotide (OctreoScan).

The 1986 nuclear reactor accident at Chernobyl caused nonuniform radiocontamination of air and land, primarily within regions of the former Soviet Union and Western Europe. Major exposure groups included the reactor workers, villagers evacuated from within 30 km of the accident, the "liquidators" who decontaminated the evacuation zone afterward, those in radiocontaminated villages not evacuated, and "others" not in the latter categories. The possibility of being exposed to radiation caused considerable anxiety, especially among pregnant women. Were teratogenic levels of radiation (> or = 0.1 Gy) exposure attained? To date there is no consistent proof that this level of radiation exposure was received. Nevertheless, thousands of induced abortions were performed. Radioiodine (I-131) caused thyroid cancer in young children in portions of Belarus, the Ukraine, and Russia. It is not known but very possible that I-131 fetal thyroid exposure contributed to this observation. The relationship between mental retardation and radiation exposure has not been confirmed. Leukemia and other cancers, while predicted for the liquidators (mainly males), has not been found in the other exposure groups at this time. Investigations of aborted fetuses and newborns in Belarus showed an increase in the frequency of both congenital and fetal abnormalities in high and low Cs-137 contaminated regions. This study is unreliable due to detection and selection biases. Accident and environmental factors unrelated to radiation doses may have contributed to these observations. Occasional positive teratogenic studies in less contaminated regions of Western Europe are suspect because of the low radiation doses received. There is no substantive proof regarding radiation-induced teratogenic effects from the Chernobyl accident.

Unlabelled: We have initiated a study in which patients suspected of having primary gliomas are given a single intracerebral injection of the thymidine analog 5-[123I]iodo-2'-deoxyuridine ([123I]IUdR). The purpose of the study is to determine the biodistribution of the radiopharmaceutical and to calculate dose estimates to the tumor and normal tissues., Methods: A patient with a cystic glioma was injected with [123I]IUdR. Whole-body scans and brain scans were obtained at various times after injection, and blood, urine and stools were collected and assayed for radioactivity to assess its biodistribution and clearance., Results: Scintigraphic imaging demonstrated that the distribution of radiolabeled IUdR was mainly confined to the tumor (injection site), stomach and bladder. Disappearance from the tumor site and blood clearance were delayed probably due to collection in the cystic lesion. Eighty percent of the injected dose was recovered in the urine., Conclusion: The pharmacokinetics of [123I]IUdR locoregionally administered to a human glioma in situ resembled those observed in a rat glioma model where administration of the radiopharmaceutical radiolabeled with the Auger electron emitter 125I was therapeutically effective.

Blocking the thyroid gland when administering radioiodinated materials is a common practice. Since pharmacologic quantities of potassium iodide (KI) in the range of 100-300 mg daily are usually administered for this purpose, the potential exists for iodide toxicity. Concomitant with the tracer administration is the risk produced from ionizing radiation. Reports in the literature demonstrated thyroid function abnormalities in patients administered iodides. Based on the latter observations the object of the present investigation is to determine the effectiveness of thyroid blocking with a lesser daily quantity of KI. Fifteen adult hip replacement patients (7 men, 8 women; 58.2 +/- 11.5 years) received 2.5 mg Ki orally every 12th hour twice daily 2 days prior to surgery and 125I-fibrinogen [(3,700 kBq)(100 microCi)], and each day up to 10 days thereafter. Thyroid and precordial counts were obtained daily and the latter two were used for calculating the 125I thyroid uptake. These data were used for estimating the thyroid blood disappearance and cancer risk. An attempt was made to compare the radiation risk to that from KI ingestion. The 125I% thyroid uptake for the study population (n = 15) was 1.83 +/- 1.25%. This compares to a thyroid uptake of 0.064 +/- 0.037% in a published report using 300 mg KI daily in the course of an 125I-fibrinogen test. The mean thyroid radiation dose for the study population was 6.09 cGy after receiving 5 mg KI daily. The specific risk estimate (SRE) for contracting thyroid cancer was calculated to be 4.5B-04. The NCRP calculated thyroid function risk after ingesting KI is 1-10E-07.(ABSTRACT TRUNCATED AT 250 WORDS)

Rationale and Objectives: Little is known about the time-related biologic behavior of radiopharmaceutical misinjections. Such inadvertent tissue infiltration of such injections may not only adversely affect a scheduled test or cause some discomfort, but potentially could produce tissue damage. Radiopharmaceutical infiltrations were assessed in a rat model., Methods: Particulate and nonparticulate radiopharmaceuticals were injected subcutaneously or intradermally into an anesthetized shaved rat model. The rate of release of the nine infiltrations per radiopharmaceutical per injection type were measured from computer data acquired with a gamma camera up to 24 hours after administration. These data were used for dosimetry determinations., Results: When injected subcutaneously, the particulate radiopharmaceutical, technetium 99m (99mTc) albumin microspheres, exhibited essentially no movement, and the soluble agents showed a biexponential release pattern. The rate of release was similar for 99mTc methylene diphosphonate (99mTc MDP) and for 67Ga citrate (67Ga), whereas thallous chloride (201Tl) exhibited the slowest release pattern. The average effective half-lives (T1/2 av-eff) were 78.3 minutes, 76.1 minutes, and 268.4 minutes, respectively. When injected intradermally, the nonparticulates exhibited a triexponential release pattern; MDP showed a more rapid release (T1/2 av-eff, 50 minutes) and 201Tl showed the slowest (T1/2 av-eff, 491.2 minutes). Absorbed doses were calculated using conventional medical internal radiation dose (MIRD) methodology for small unit density spheres. The absorbed dose was greatest for a 201Tl infiltration. A 201Tl infiltrate of 1 mCi per gm of tissue is capable of producing radiation-absorbed doses greater than 500 rads. Additional studies were performed with heat, hyaluronidase, and volume dilution in an attempt to accelerate the rate of release of 201Tl. Local heat application proved to be more efficient than volume change or hyaluronidase application., Conclusion: These data indicate an insignificant skin radiation burden from the majority of nonparticulate infiltrated radiodiagnostic agents. Thallium 201, however, has the potential to produce significant radiation burdens when infiltrated at high specific activity. Actual human infiltration release rates may differ because of variants in blood flow and assumed infiltration volume relative to the animal model.

Gaucher's disease is a lysosomal storage disease in which cells of the reticuloendothelial system accumulate the lipid glucocerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. We monitored the rate of inhaled 133Xe uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. Twenty-two patients (15 adults, 7 children) with various degrees of previously diagnosed Gaucher's disease were positioned supine under a gamma-camera interfaced to a computer system. All patients rebreathed 133Xe gas from a closed system for 10 min followed by 14 min of wash-out. Digitized images of the lung, liver, spleen, bony sites and soft tissue were obtained at 1 min intervals during the wash-in and wash-out phases. Counts for each ROI were normalized per 100 pixels and plotted as a function (time). Maximum uptake was also calculated by relating the counts/ROI/100 pixels to the 10 min integrated lung count during equilibrium (the administered "dose"). There was essentially no 133Xe uptake in liver and spleen involved with Gaucher's disease. Monophasic uptake and biphasic wash-out curves were observed in the limited investigative population. Skeletal Gaucher deposits released the 133Xe at a greater rate relative to soft tissue.

Rationale and Objectives: The communication of a suitable radiation risk consent form statement to a potential research subject has always been difficult to formulate. Concomitant with this is the equally problematic task of ensuring that subjects understand the true risks of the study. In an effort to document how other Institutional Review Boards (IRBs) express radiation risk associated with participating in a research investigation, a questionnaire was developed and was sent to 23 large medical-research institutions., Methods: Questions pertained to the manner of comparing risk, units for expressing radiation dose, patient population differentiation, and statements for given situations. In addition, each institution was asked to provide examples of radiation-related in-house consent form statements. Thereafter, the examples were forwarded to the responding institutions for grading., Results: Fourteen responses were received and summarized. The majority compared the study test to a similar radioactivity study, Nuclear Regulatory Commission (NRC) occupational limits and/or Radioactive Drug Radiation Committee (RDRC) limits. There was an equal distribution of radiation units used; absorbed dose, dose equivalent, and effective dose equivalent. The majority of respondents did not differentiate between normal individuals and patient volunteers. Included in the 14 responses were 46 in-house generated radiation-related consent form statements. The latter were assembled and forwarded to the 14 responding institutions with instructions to "approve" or "disapprove" each. Nine statements obtained an 80% or greater acceptance rating, with three > 90%. The remaining were overwhelmingly rejected as suitable radiation risk statements., Conclusions: Based on the submitted material and statement grading results, recommendations were formulated toward producing a standard format for expressing radiation risk in the consent form. Effective dose equivalent in comparison to annual natural environmental radiation or occupational radiation dose limits were recommended based on these data. While an "optimum" radiation risk consent form statement may not be attainable, these results nevertheless provide recommendations based on a consensus of practitioners in the field.

A review of the literature pertaining to the human dosimetry of 201Tl-labelled thallous chloride provides a spectrum of organ absorbed doses associated with this radiopharmaceutical. A more recent article details human quantitative studies up to 216 h postadministration. This multiorgan radiopharmacological study, however, reports the kidney dosimetry to be significantly lower than previous values; 0.0647 mGy MBq1 (0.238 rad mCi-1) compared to 0.326 mGy MBq-1 (1.2 rad mCi-1). Because of the latter discrepancy the dosimetry was recalculated using the reported pharmacodynamic data. This recalculation resulted in a kidney radiation dose comparable to previously published reports of 0.514 mGy MBq-1 (1.89 rad mCi-1). Also, revised absorbed doses to the various segments of the gastrointestinal tract (GIT) were significantly higher.

A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expert knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team.

Efficient control over the purchase and receipt of radioactive material is a necessary part of any radiation safety program. We describe a novel computerized method for monitoring the flow of radioactive material within a large broad-licensed medical research complex. The Local Area Network (LAN) described interfaces the radiation safety office with radionuclide receiving, the authorized user, grants and contracts, special accounts, and purchasing. Task-specific software enables the authorized user to place an order and allows the monitoring of possession/ordering limits, personnel, date of order, and time of receipt via the screen. The resultant data base is easily annexed for specific information. The system is user-friendly and adaptable to any set of circumstances.

Magnetic resonance imaging uses powerful magnetic fields and a radiofrequency pulse to provide a diagnostic image. Physicians must identify patients with metallic internal implants, pacemakers and cochlear implants before MRI scanning to prevent serious injury. Some patients also experience severe anxiety from the confinement and noise during the examination. Careful evaluation of these potential problems should always be undertaken before performing an MRI examination.

The simultaneous measurement of tracer resorption and apposition in a rat fracture model was accomplished with 99mTc labeled methylene diphosphonate (99mTc-MDP) and 125I labeled phenylphosphonic acid (125I-phi PA), respectively. Loss of 125I-phi PA from the fracture site showed a biexponential release pattern; I = 31% (t1/2b = 2.0 d) and II = 69% (t1/2b = 55.4 d). 99mTc MDP temporal apposition at the fracture site followed the law of allometric growth (y = bxk) with k = 7.75, 10 days post injury. The 125I-phi PA loss differed significantly (P less than 0.001) when compared to normal bone which exhibits a monoexponential release with a t1/2b = 962 days. In the rat tibia fracture model investigated, bone apposition significantly (P less than 0.001) dominates over bone resorption as a function of time. This overwhelming difference partially accounts for the healing process. The apposition-resorption comparison may be a useful index for following the course of skeletal pathology for a variety of model systems.

The nuclear physics and chemical properties of technetium-99m are reviewed. The review of basic nuclear physics includes: classification of nuclides, nuclear stability, production of radionuclides, artificial production of molybdenum-99, production of technetium 99m and -99Mo-99mTc generators. The discussion of the chemistry of technetium includes a profile of several -99mCc-labeled radiopharmaceuticals.

The dosimetry associated with orally administered [99mTc]sulfur colloid for the diagnosis of gastroesophageal reflux has not been adequately described for the pediatric populations. Standard MIRD methodology was performed for the following: newborn, 1, 5, 10, and 15 yr old, and adult standard man. The critical organ for all pediatric groups was the lower large intestine with absorbed dose of 0.927, 0.380, 0.194, 0.120 and 0.0721 rad/100 microCi, respectively. For the adult the critical organ was the upper large intestine with an absorbed dose of 0.0518 rad/100 microCi. These data should be considered when administering [99mTc]sulfur colloid orally in a pediatric population.

Cardiac catheterization with angiography can deliver the greatest dose of x-radiation of any diagnostic medical examination. The physicians and technologists in the angiography room receive low-level scattered radiation over a period of months to decades. Although the radiobiology is complex, the physicians who perform cardiac catheterization should be familiar with the potential genetic and somatic effects of radiation and with the methods to reduce or eliminate x-ray exposure. The aim of radiation protection criteria is to reduce the risk of cancer death to less than the fatality risk for other occupations regarded as safe. This report is a review of the literature relating to radiation exposure and protection in cardiac catheterization laboratories. Catheterization personnel have control over the time duration of exposure, placement of technologists, shielding, location of equipment and monitoring of dose received.

Whole body retention (WBR) of 99mTc labeled methylene diphosphonate (MDP) has been shown to significantly differentiate various clinical stages of prostate cancer. Whole body measurements, when performed at 5 min and 24 h after i.v. administration of 99mTc-MDP, allows for the calculations of percentage whole body retention (% WBR) after one day. The latter can be expressed relative to either the anterior or posterior projection, or in combination as the geometric mean value. In an attempt to better describe the clinical course of prostate cancer patients with bone metastases we have refined the % WBR calculations to include a normalization factor. The latter consists of the mean 24-h value of WBR's as obtained from 10 prostate cancer patients without bony metastases as determined by bone scintigram. These values were determined for each projection to be: anterior = 26.5 +/- 4.7%, posterior = 37.5 +/- 7.4%, and geometric mean = 31.5 +/- 5.7%. The % WBR is then divided by the normalization factor of choice and expressed as (% WBR)N. These data are used to better express 99mTc MDP 24-h whole body retentions when following the clinical course of patients with metastatic carcinoma of the prostate. Caution should be exercised when interpreting these data when metabolic bone pathology is present. A false negative (% WBR)N value will result if an infiltration of the 99mTc-MDP occurs during administration.

A quantitative gamma-camera technique is used to calculate the percentage of administered activity taken up by various areas of the skeleton. The method uses an external standard source of activity as a reference, and in addition presents the information in a new format, the Organ Uptake Image (OUI). Two cases of Paget's disease serve to illustrate the usefulness of this approach to quantitative bone imaging.

A simple technique for determining the whole body retention of 99mTc labeled methylene diphosphonate (MDP) at 4-h and 24-h was applied to 28 adult patients (22 prostate cancer, 6 osteoporosis). Following administration of 20 mCi (740 MBq) 99mTc-MDP, a qualitative scintigram was performed and whole body retention was recorded at 4 and 24 h. The prostate cancer patients all had positive bone scintigrams, and of this group, 7 were in relapse and 15 in remission on chemotherapy. The osteoporotic groups whole body retention values were determined prior to the initiation of drug therapy. Mean percent whole body retention values were significantly greater at 4 and 24 h for the cancer patients in relapse relative to both the prostate cancer patients in remission and the osteoporotics: 4-h%/24-h%; equals 74.3/60.2, 57.5/33.5, and 48.0/30.3, respectively. The whole body retention values of the latter two groups, however, were only significantly different at 4-h. An additional index of skeletal pathology was developed by combining the 4-h/24-h values to calculate the biological half time (t1/2b) for this time period using a single exponential model. Again the cancer patients in relapse exhibited a significantly longer half time relative to those in remission and the osteoporotics (70.4 vs 25.7 h and 29.2 h, respectively). The combination of 4 and 24-h whole body retention values with the associated t1/2b has potential for following and classifying patients during the course of their skeletal disease. These values have been shown to be especially valuable with cancer patients with metastatic disease.

Several lines of human tumor cells in monolayer and soft agar cultures allow permeation of low levels of adenine nucleotides through their plasma membranes, while, in general, untransformed cells do not incorporate adenine nucleotides into their cellular pools without prior degradation of the nucleotides to adenosine. This study determined the uptake of 99mTc-radiolabeled chelated forms of adenine nucleotides, 99mTc-Ap4A (diadenosine 5',5"',P1,P4-tetraphosphate) and 99mTc-ATP chelates as radiodiagnostic agents suitable for the in vivo detection of tumors by radionuclide imaging. Biodistribution studies revealed that Ap4A accumulated preferentially in RT-24 tumors implanted in rats and that V2 carcinoma implanted in rabbits could be readily visualized by in vivo imaging. The biodistribution at various time points showed increased tumor-to-muscle ratios after 99mTc-Ap4A or 99mTc-ATP injections when compared with a nonspecific marker of the extracellular fluid space, 99mTc-labeled diethylenetriaminepentaacetic acid and with an agent known to localize in some tumors, 67Ga-labeled citrate. Studies of ectoenzymatic activities of virus-transformed animal cells and their untransformed counterparts in monolayer cultures showed marked decreases in the ectoenzymatic activities that degrade Ap4A in the transformed cells. Incorporation of en bloc [3H, 32P]Ap4A into cellular acid-soluble nucleotide pools of certain transformed cells was observed. Normal untransformed cells incorporated the radioactive label only by prior degradation to [3H]adenosine and 32Pi.

A formulation of 14C-lomustine in propylene glycol-ethanol (4:1) was administered intravenously to rats infiltrated with glioma tumors of the astrocytic series (RT6). The organ and tumor distribution of this agent was followed at 1, 4, 12, and 24 hr. Rapid blood disappearance (0-1 hr) of the label concomitant with an increase in all organs except the lung, muscle, and brain was observed. Only the blood, liver, and muscle contained greater than 1% of the dose after 24 hr. The bladder, liver, small bowel, and kidneys concentrated the highest percentages throughout the study. The distribution of 14C-lomustine in the tumor relative to the brain, muscle, and blood showed a maximum 4-12 hr after administration.

Thyroid screening measurements for 131I were performed on 58 travelers returning from Eastern and Western Europe to Boston after the Chernobyl reactor accident on April 26, 1986. The travelers consisted of both Americans arriving home after business or vacation and European nationals visiting relatives in the Boston area. For purposes of dosimetry the population was divided into three subpopulations--adult (greater than 18 yr old), children (less than or equal to 18 yr old), and two individuals, 17 and 26 wk pregnant. Seventy-four percent of the population had detectable quantities of 131I thyroid burdens, ranging from 1 nCi (37 Bq) to 900 nCi (33,300 Bq). The highest adult radiation dose equivalent was 5.18 mrem (51.8 mSv). The children, however, had considerably higher dose equivalents with one infant receiving 37 rem (370 mSv). Several other children were above 1 rem (10 mSv). The fetal dose equivalents were less than 14 mrem (140 mu Sv). The presence of rain dominated those testing positive for 131I. Radioactive fallout from the Chernobyl accident contaminated a wide range of Europe and a large population subsequently ingested radioactivity. The children exhibited the highest thyroid radiation dose equivalents of the individuals monitored in the present study. The significance of this is presently unknown.

A small proportion of radiopharmaceutical administrations are extravasted from the injection site to the surrounding tissue. Of interest is the resulting absorbed dose. This investigation was undertaken to determine the biologic behavior and subsequent dosimetry of selected radiopharmaceutical infiltrations using a rat model. Subcutaneous injection of 99mTc-microspheres, 99mTc-MDP, 67Ga-citrate, and 201Tl-chloride were studied. Three adult male Sprague-Dawley rats were injected subcutaneously at three separate sites on the shaven backs of the animals for each agent studied (i.e., nine sites per agent). The rats were imaged and the resulting data were analyzed by computer immediately after injection and at various intervals up to 5-6 h, and again at 24 h. Particulate subcutaneous 99mTc-microspheres exhibit essentially no diffusion of tracer from the injection site, whereas non particulates showed a biexponential release pattern. Radiation burdens in rad/mCi (mGy/MBq) due to an infiltrate volume uniformally distributed over a 5 g mass for 99mTc-microspheres, 99mTc-MDP, 67Ga-citrate and 201Tl-chloride were 59.4(16.0), 13.6(3.7), 32.9(8.9) and 92.2(24.9), respectively. The radiobiological risk associated with these radiation burdens are below that needed to produce severe skin reactions when distributed within a 5 g mass.

The concentration of 125I-phenylphosphate (I phi PA), a long-lived bone-seeking radio-pharmaceutical (T1/2 biol = 962 days) that localizes in acute infarction (MI), was studied in 30 rats after ligation of the anterior descending coronary artery. At 23 h postMI, I phi PA was given intravenously to all animals, and five of this group received 99Tcm-pyrophosphate (99Tcm-pyro) intravenously. These five rats were sacrificed 2 h later and the content of I phi PA and 99Tcm-pyro activities was determined for normal and infarcted (INF) heart segments. There is a zone of INF that contains residual I phi PA which also concentrates 99Tcm-pyro consistently after MI. This zone may represent jeopardized myocardium which has not undergone complete necrosis.

A formulation of 1-[2-chloroethyl-U-14C]-3-cyclohexyl-1-nitrosourea in ethanol:propylene glycol (1:4, v/v) was administered to rats previously infiltrated with RT6 glioma tumors (astrocytic series); the organ and tumor tissue distribution was followed at 1, 4, 12, and 24 hr postinjection. From 0 to 1 hr, rapid blood disappearance of the 1-[2-chloroethyl-U-14C]-3-cyclohexyl-1-nitrosourea was observed with a concomitant increase in all organs except the lung, muscle, and brain. After 24 hr, only the blood, liver, and muscle contained < 1% of the dose. Throughout the study, the bladder, liver, small intestine and kidneys concentrated the highest percentages on a per-gram basis. The distribution of 1-[2-chloroethyl-U-14C]-3-cyclohexyl-1-nitrosourea in the tumor relative to brain, blood, and muscle showed a maximum 4 to 12 hr after administration.

Twenty-four outbred cats underwent massive osteoarticular allograft and control autograft transplantation, using the right distal femur with its articular cartilage, capsule, and medial collateral ligament intact. The cats were monitored clinically and radiographically for 1 year. Groups of cats (4 allografts and 2 control autografts) were euthanatized at 3-, 6-, 9-, and 12-month intervals. At necropsy, the grafts were photographed and assessed for bone healing and replacement by standard radiography, quantitative 99mTc bone scans, microradiography, and histologic examination of decalcified and nondecalcified specimens. The osteosynthesis site of the allografts usually healed by 5 months, compared with the autografts that healed by 3 months. As illustrated by quantitative bone scans, creeping appositional new bone slowly invaded and replaced the allograft bone. Seemingly, the cat can be used as an acceptable and clinically comparable model for the massive osteoarticular allografts currently being used for the reconstruction of joints damaged or destroyed by neoplasm surgery in limb-sparing procedures in human beings. This model may also be used to assess the rate and method of bone healing.

In the past several years bone imaging has become a routine diagnostic tool for the nuclear medicine clinician. However, increased information may be derived by determining the ratio-pharmacokinetic parameters associated with blood, urine, and bone. In an adult male population of normals (N = 5--6) blood clearance, urinary excretion, and skeletal uptake of 99mTc-Diphosphonate were determined as a function of time after intravenous (i.v.) administration. The quantitative imaging studies (lower lumbar region) were performed up to 1 h post administration with a scintillation camera interfaced to a computer. Blood levels exhibited a triexponential clearance pattern and urinary excretion of the radiopharmaceutical was essentially complete by 4 h. The computer-generated images showed an initial early uptake in bone, kidneys, and soft tissue. Thereafter, a parallel fall-off in activity was observed in kidneys and soft tissue, with a concomitant increase in bone.

The biodistribution, kinetics, imaging characteristics and blood flow correlations of 99mTc labeled DiArs and DMPE were studied. The mice biodistribution were compared to 201Tl in mice and dogs, respectively. The myocardial kinetics of these agents were evaluated in normal and ischemic myocardium using miniaturized endocardial detectors. DiArs had a lower myocardial concentration (9.4 +/- 0.8% dose/g at 1 min), than DMPE (11.7 +/- 1.1% dose/g at 1 min) but both were considerably less than 201Tl (23-26% dose/g at 1 min). The kinetic characteristic of both technetium labeled agents suggested that redistribution into ischemic myocardium would not take place, since the clearance rate from normal and ischemic myocardium was similar for both the DiArs and DMPE . The clear visualization of the canine myocardium after i.v. injection demonstrated the superiority of DMPE over DiArs and the potential use of these agents, if proven, to behave the same in human trials.

A simple technique for measuring 24-h whole-body retention (24-h WBR) of 99mTc-labeled methylene diphosphonate (MDP) is described. We chose a standard thyroid probe-scaler system (Picker-Magna Scanner) as our counting instrument and characterized it relative to: photon saturability; optimum counting time post administration; patient positioning; and results with prostate cancer patients with positive/negative scintigram diagnoses for bone metastases. Whole body retention values of 99mTc at 24 h were easily measured with our instrumentation. Initially whole body count rates were determined at 5-min post injection and, again at 24 h. Data accumulated prior to the 5-min time period were inaccurate due to a higher sensitivity for the activity in the early circulation. Also, initial count rates obtained from patients injected with (740 MBq) (20 mCi) 99mTc-MDP usually required a correction due to detector saturation. The data observed at 24 h, representing skeletal tracer uptake, required no such correction. Patient positioning was rigorously controlled for the two time intervals to insure constant geometry. The 24 h-WBR values measured for prostate cancer patients with positive bone scintigrams was significantly different from those patients with negative scintigrams (58.8 +/- 8.7% and 29.2 +/- 9.6% respectively). Measurement of the 24 h-WBR has great potential for following various pathologies in the clinical setting.

The status of patients with skeletal metastases from prostatic carcinoma was determined from a quantitative uptake and retention measurement of the bone scanning radiopharmaceutical 99mtechnetium-methylene diphosphonate. Whole body counts were performed 5 minutes and 24 hours after intravenous administration of 99mtechnetium-methylene diphosphonate, and were expressed as the percentage uptake by the skeleton at 24 hours. Skeletal uptake determinations were done in 29 patients with prostatic cancer (17 with osseous metastases) who were evaluated at 3 to 6-month intervals. Group 1 consisted of patients who responded to therapy and achieved remission, group 2 included patients with relapse or progressive disease, group 3 consisted of those with metastases who were in remission for longer than 6 months and group 4 included those without evidence of any bony metastases. The baseline mean +/- standard deviation 24-hour skeletal uptake values were 46.1 +/- 12.0 per cent in group 1, 34.3 +/- 13.9 per cent in group 2, 27.0 +/- 5.9 per cent in group 3 and 28.9 +/- 5.5 per cent in group 4. At 3 to 6 months the values in group 1 (responders) decreased by 18 per cent, while those in group 2 (relapse or progression) increased by 19 per cent and those in group 3 (remission) increased by 1.5 per cent. The quantitative 24-hour skeletal uptake test was performed easily, reproducible and at least as useful as concurrent chemical blood tests and subjective bone scan interpretations.

A skeletal seeking radiopharmaceutical labeled with a long-lived radionuclide was developed to evaluate regional bone formation and its subsequent resorption. The agent is [phosphonate (phenylmethylene hydroxy) bis] - I-125 or I-125 phi PA. Tissue distribution studies in mice (N = 16) showed approximately 40% of the administered dose to be retained by the skeleton up to 336 hours post IV injection. The percentage of the dose accumulated by the thyroid gland remained at less than 0.5%, indicating minimal deiodination of the I-125 phi PA. Whole body retention studies in the same species revealed a triexponential release pattern with the longest component comprising 33% of the dose with a biologic half-life of 962 days. A fractured rat tibia model was studied with I-125 phi PA and Tc-99m MDP. Chronic loss of the I125 phi PA relative to normal tibia was quantitated: five days (62.8%); 30 days (47.4%). Concomitant increased uptake of the Tc-99m MDP was observed at the fracture site relative to normal: five days (186%); 30 days (1,041%). The above data suggest that I-125 phi PA can be utilized to measure acute bone formation and chronic resorption.