Radioactivity in breast milk following 111In-octreotide.

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).

Teratogen update: radiation and Chernobyl.

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.

Radiation exposure from gallium-67-citrate patients.

OBJECTIVE: Serial monitoring of patients was performed to determine the radiation exposure contributed by patients injected with 67Ga-citrate to their surroundings. Radiology and nursing staff distance exposure estimates were made for various patient care tasks and imaging tests. METHODS: Fifteen adult patients were surveyed early (mean 4.3 min) and 11 of the 15 were surveyed at 3 d (mean 68.8 h) postinjection. The standard adult lymphoma imaging activity of 333-407 MBq (9-11 mCi) resulted in a range of 3.7-8.1 MBq/kg (0.1-0.22 mCi/kg). Dose rate measurements were made in the anterior, posterior, and left and right lateral projections at the level of the umbilicus, at distances of patient's surface and at 30.5 cm and 100 cm with a calibrated ion chamber. Time of contact-routine task analyses also were obtained for nursing and radiology personnel. Using a radiation survey-derived biexponential pharmacokinetic relationship, radiation exposures were determined for hospital personnel and family members at various times after injection. RESULTS: Based on the study population survey results, the mean instantaneous exposures (microSv/h) for an administered activity of 370 MBq (10 mCi) 67Ga-citrate were determined. The task analyses revealed the maximum patient contact time for any procedure performed at a distance equal to, or less than, 30.5 cm was 30 min. CONCLUSION: The quantitation of radiation exposure scenarios from 67Ga-citrate patients has determined that no special precautions are necessary for medical personnel when performing routine tasks associated with these patients.

2-aminoethylphosphonic acid: biodistribution of a naturally occurring phosphonate after labelling with technetium-99m.

Phosphonic acid derivatives (P-C-P bond) are thought to be devoid of a mammalian synthetic pathway. Nevertheless, a natural phosphonate derivative, 2-aminoethylphosphonic acid (2-AEP), has been detected in animal and human tissue. After labelling with 99Tcm, biodistribution studies were performed in normal and tumour-bearing rats. A scintigraphic rabbit investigation was also completed. When expressed as percent injected dose per gram, the lung, liver, kidney and bone concentrated > 1% of the 99Tcm-2-AEP at 5 min. By 6 h, the liver, bone, marrow and kidney dominated. The 2 h rabbit scintigraphic image coincided with the rat data. Tumour-to-organ ratios showed values intermediate with those obtained with 99Tcm-diphosphonate and 99Tcm-pertechnetate. 99Tcm-2-AEP may show promise as a soft tumour scintigraphic agent because of its unique structure and low gastrointestinal uptake, provided the relatively short t1/2p of 99Tcm proves to be suitable.

Intratumoral administration of 5-[123I]iodo-2'-deoxyuridine in a patient with a brain tumor.

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.

A software application to estimate exposure around 131I cancer and hyperthyroid patients.

A Windows-based software application (IDOSE) has been developed to estimate time-dependent radiation exposure around patients who receive 131I-sodium iodide (NaI) for hyperthyroidism or thyroid cancer therapy. This application is based on radiation exposure associations which relate pharmacokinetically such factors as administered dose, distance from patient, directional projection and time. The software was tested by comparing its predictability with that obtained with a survey meter in-house as well as at neighbouring hospitals for a total of 74 patients who were administered 131I(NaI). The latter surveys were performed at the patient's surface, at 30 cm and at 100 cm, from 0.25 to 56 h post-administration for a total of 133 data points. Statistical testing showed r-coefficients of > 0.9 and paired t-test values of > 0.39 between the predicted and measured survey values for all distances surveyed. The versatility of IDOSE lies in its ability to predict radiation exposure to others who come into contact with the patient relative to projection, time and distance. The latter is based on patient- and literature-generated default values at administration for three distances: surface, 30 cm and 100 cm. Thereafter, IDOSE predicts exposures at the default distances as a function of time. User-generated survey values at administration are an input option. IDOSE will never take the place of an actual survey. Its potential lies with estimating such information at times when surveys are not possible. Hypothetical 131I(NaI) patients are followed to illustrate the multifaceted nature of IDOSE. This paper describes the development, implementation and efficacy of a user-friendly Windows-based software application for predicting radiation exposure around 131I(NaI) patients.

Biodistribution and dosimetry of indium-111-polyclonal IgG in normal subjects.

UNLABELLED: Indium-111-polyclonal IgG is a new imaging agent of infection and inflammation that has been developed as a possible replacement for radiolabeled leukocytes. We undertook a study to determine the safety, biodistribution and dosimetry of the agent in normal subjects. METHODS: Twelve normal male volunteers with an average age of 34 yr (range 21-55 yr) were studied. Each was injected with 1.22-1.47 mCi 111In-labeled polyclonal IgG; digital whole-body images, in addition to blood, urine and fecal samples, were obtained immediately after injection and at 6, 24, 48, 72, 96 and 120 hr. Whole-body counts, as well as individual organ data obtained by outlining regions of interest, were measured. Blood, urine and fecal counting were done in a well counter and compared to known standards; dosimetry calculations were performed with the MIRD technique. RESULTS: The mean whole-blood activity had a two-phase disappearance curve: the T1/2I was 11.4 hr (61.1%) and the T1/2II was 112.5 hr (38%). Twelve percent of the dose was excreted in the urine and 1.14% in the feces. Skeletal muscle had the highest percentage of uptake, followed by the bone marrow, liver and lungs; the spleen showed less than 1% uptake. Activity in the lungs varied with time, falling by 37% after 18 hr and by 68% after 72 hr. Dosimetry calculations indicated that the highest absorbed dose was to the liver (1.42 rad/mCi) followed by the testes (1.23 rad/mCi) and red marrow (0.976 rad/mCi). The total-body dose was 0.467 rad/mCi, with an effective dose equivalent of 790.84 mrem. CONCLUSION: The biodistribution of 111In IgG is similar to that of 99mTc-HMPAO-labeled leukocytes. Activity in the liver, kidneys and GI tract may make evaluation of infection in these regions difficult. The dosimetry data indicate that adequate doses can be administered for clinical imaging without exposing the patient to excessive radiation.

125I-fibrinogen: thyroid blocking with 2.5 mg potassium iodide twice daily in patients after hip surgery.

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)

Dosimetric consequences of radiopharmaceutical infiltrations.

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.

Radiopharmacology of inhaled 133Xe in skeletal sites containing deposits of Gaucher cells.

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.

An attempt to standardize the radiodiagnostic risk statement in an Institutional Review Board consent form.

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.

201Tl-labelled TlCl dosimetry revisited.

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.

Quantitative imaging of Gaucher disease.

Twenty-three patients with type 1 Gaucher disease were evaluated with a battery of quantitative imaging techniques. Plain radiographs were used to measure cortical thickness and Erlenmeyer flask deformity. Xenon-133 uptake was measured in scans of the lower extremities. Dual-energy quantitative computed tomography was used for calculation of trabecular bone and bone marrow fat content in the spine and long bones. Magnetic resonance (MR) imaging was performed to evaluate disease extent and three-dimensional splenic volume. MR images were also used to provide quantitative measurements of each vertebral fat fraction. Each imaging modality was correlated with the others as well as with the clinical history of skeletal complications and the hematocrit and acid phosphatase activity. There was a strong relationship between splenic volume and disease severity as measured clinically and with laboratory testing. The spinal fat fraction also correlated with these measures of disease severity and with the femoral fat fraction and xenon uptake. No measurement allowed discrimination of patients with from those without skeletal complications.

Audits of radiopharmaceutical formulations.

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.

A local area network for controlling the ordering and purchasing of radioactive material.

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.

Hazards of magnetic resonance imaging.

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 infiltrated radiopharmaceutical injection: dosimetric considerations.

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.