Robert E. Reiman

The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia.

The cyclotron-produced radionuclide, 13N, was used to label ammonia and to study its metabolism in a group of 5 normal subjects and 17 patients with liver disease, including 5 with portacaval shunts and 11 with encephalopathy. Arterial ammonia levels were 52-264 micron. The rate of ammonia clearance from the vascular compartment (metabolism) was a linear function of its arterial concentration: mumol/min = 4.71 [NH3]a + 3.76, r = +0.85, P less than 0.005. Quantitative body scans showed that 7.4 +/- 0.3% of the isotope was metabolized by the brain. The brain ammonia utilization rate, calculated from brain and blood activities, was a function of the arterial ammonia concentration: mumol/min per whole brain = 0.375 [NH3]a - 3.6, r = +0.93, P less than 0.005. Assuming that cerebral blood flow and brain weights were normal, 47 +/- 3% of the ammonia was extracted from arterial blood during a single pass through the normal brains. Ammonia uptake was greatest in gray matter. The ammonia utilization reaction(s) appears to take place in a compartment, perhaps in astrocytes, that includes less than 20% of all brain ammonia. In the 11 nonencephalopathic subjects the [NH3]a was 100 +/- 8 micron and the brain ammonia utilization rate was 32 +/- 3 mumol/min per whole brain; in the 11 encephalopathic subjects these were respectively elevated to 149 +/- 18 micron (P less than 0.01), and 53 +/- 7 mumol/min per whole brain (P less than 0.01). In normal subjects, approximately equal to 50% of the arterial ammonia was metabolized by skeletal muscle. In patients with portal-systemic shunting, muscle may become the most important organ for ammonia detoxification. Muscle atrophy may thereby contribute to the development of hyperammonemic encephalopathy with an associated increase in the brain ammonia utilization rate.

Radiation Dose to the Female Breast from 16-MDCT Body Protocols

OBJECTIVE The objective of our study was to determine the radiation dose to the female breast from current 16-MDCT body examinations. MATERIALS AND METHODS Metal oxide semiconductor field effect transistor (MOSFET) detectors were placed in four quadrants of the breast of a female-configured anthropomorphic phantom to determine radiation dose to the breast. Imaging was performed on a 16-MDCT scanner (LightSpeed, GE Healthcare) using current clinical protocols designed to assess pulmonary embolus (PE) (140 kVp, 380 mA, 0.8-sec rotation, 16 x 1.25 mm collimation), appendicitis (140 kVp, 340 mA, 0.5-sec rotation, 16 x 0.625 mm collimation), and renal calculus (140 kVp, 160 mA, 0.5-sec rotation, 16 x 0.625 mm collimation). RESULTS Radiation dose to the breast ranged from 4 to 6 cGy for the PE protocol and up to 1-2 cGy in the inferior aspect of the right breast and lateral aspect of the left breast for the appendicitis protocol. The renal calculus protocol yielded less than 150 microGy absorbed breast dose. CONCLUSION Current clinical chest and abdomen protocols result in vairable radiation doses to the breast. The magnitude of exposure may have implications for imaging strategies.

Cumulative Radiation Exposure and Cancer Risk Estimation in Children With Heart Disease

Background— Children with heart disease are frequently exposed to imaging examinations that use ionizing radiation. Although radiation exposure is potentially carcinogenic, there are limited data on cumulative exposure and the associated cancer risk. We evaluated the cumulative effective dose of radiation from all radiation examinations to estimate the lifetime attributable risk of cancer in children with heart disease. Methods and Results— Children ⩽6 years of age who had previously undergone 1 of 7 primary surgical procedures for heart disease at a single institution between 2005 and 2010 were eligible for the study. Exposure to radiation-producing examinations was tabulated, and cumulative effective dose was calculated in millisieverts. These data were used to estimate lifetime attributable risk of cancer above baseline using the approach of the Committee on Biological Effects of Ionizing Radiation VII. The cohort included 337 children exposed to 13 932 radiation examinations. Conventional radiographs represented 92% of examinations, whereas cardiac catheterization and computed tomography accounted for 81% of cumulative exposure. Overall median cumulative effective dose was 2.7 mSv (range, 0.1–76.9 mSv), and the associated lifetime attributable risk of cancer was 0.07% (range, 0.001%–6.5%). Median lifetime attributable risk of cancer ranged widely depending on surgical complexity (0.006%–1.6% for the 7 surgical cohorts) and was twice as high in females per unit exposure (0.04% versus 0.02% per 1-mSv effective dose for females versus males, respectively; P<0.001). Conclusions— Overall radiation exposures in children with heart disease are relatively low; however, select cohorts receive significant exposure. Cancer risk estimation highlights the need to limit radiation dose, particularly for high-exposure modalities.

Intratumoral consumption of indium-111 labeled platelets in a patient with hemangiomatosis and intravascular coagulation (Kasabach-Merritt syndrome)

Previous studies regarding sites of platelet destruction in patients with the Kasabach‐Merritt syndrome are conflicting. The authors recently studied an adult patient with multiple large hemangiomata, thrombocytopenia, and intravascular coagulation by external imaging following the injection of autologous Indium‐111 labeled platelets. Sequential images showed prompt accumulation of platelet‐associated radioactivity in areas within the right hemithorax which corresponded to certain tumors noted on the chest roentgenogram. Despite the presence of multiple other lesions in bone and soft tissues, platelet radioactivity was otherwise normally confined to liver and spleen. Using data obtained from serial images, it was shown that radioactivity within the thoracic masses actually increased over time. These data indicate that platelet consumption occurred as an active process and that localization was not a result of tumor vascularity. It is concluded that platelets are locally consumed within certain hemangiomata. However, within the same individual, there may exist considerable heterogeneity among these tumors with respect to platelet‐trapping ability. In similar patients with multiple tumors, indium‐platelet scanning might be used to direct local therapy to particular lesions in an effort to correct the thrombocytopenia. Cancer 52:256‐2260, 1983.

9:30—9:45: Preliminary Evaluation of F-18 Fluorocholine (FCH) as a PET Tumor Imaging Agent

The purpose of this study was to develop and evaluate an F-18 labeled choline tumor imaging agent.FCH was synthesized through the intermediate F-18 fluorobromomethane that was used to alkylate dimethylethanolamine. The isolated FCH was evaluated in PC-3 human prostate cancer cells, PC-3 human prostate cancer xenograft studies, and human prostate and brain tumor patients.FCH was accumulated at a slightly lower rate than FDG in the cultures of PC-3 cells. Inhibition of choline transport and phosphorylation by hemicholinium-3 resulted in a 90% decrease in FCH uptake without altering FDG uptake. FCH had a similar biodistribution as C-14 choline in mice, with the liver and kidneys being the primary sites of uptake. Tumor uptake of FCH and FDG were comparable at 45-60 mins after injections. The tumor:blood ratio was higher for FCH (5.3 +/- 2.4) than for FDG (3.2 +/- 0.3). Brain uptake of FCH was 10% that of FDG. FCH-PET studies were compared to FDG-PET studies. In the prostate cancer patients, more lesions have been seen on the FCH studies than on the FDG studies, and the standardized uptake values (SUV) have been higher with the FCH. Decreases in FCH-PET SUV have been noted in patients treated by androgen deprivation. Patients with suspected recurrent brain tumors have had more clearly defined abnormal accumulation on the FCH-PET scans than on the FDG-PET scans. The FCH is not accumulated by normal cortex.FCH is a promising imaging agent for the evaluation of metastatic prostate cancer and recurrent brain tumor.

Preliminary evaluation of F-18 fluorocholine (FCH) as a PET tumor imaging agent

The purpose of this study was to develop and evaluate an F-18 labeled choline tumor imaging agent.FCH was synthesized through the intermediate F-18 fluorobromomethane that was used to alkylate dimethylethanolamine. The isolated FCH was evaluated in PC-3 human prostate cancer cells, PC-3 human prostate cancer xenograft studies, and human prostate and brain tumor patients.FCH was accumulated at a slightly lower rate than FDG in the cultures of PC-3 cells. Inhibition of choline transport and phosphorylation by hemicholinium-3 resulted in a 90% decrease in FCH uptake without altering FDG uptake. FCH had a similar biodistribution as C-14 choline in mice, with the liver and kidneys being the primary sites of uptake. Tumor uptake of FCH and FDG were comparable at 45-60 mins after injections. The tumor:blood ratio was higher for FCH (5.3 +/- 2.4) than for FDG (3.2 +/- 0.3). Brain uptake of FCH was 10% that of FDG. FCH-PET studies were compared to FDG-PET studies. In the prostate cancer patients, more lesions have been seen on the FCH studies than on the FDG studies, and the standardized uptake values (SUV) have been higher with the FCH. Decreases in FCH-PET SUV have been noted in patients treated by androgen deprivation. Patients with suspected recurrent brain tumors have had more clearly defined abnormal accumulation on the FCH-PET scans than on the FDG-PET scans. The FCH is not accumulated by normal cortex.FCH is a promising imaging agent for the evaluation of metastatic prostate cancer and recurrent brain tumor.

Lifetime Attributable Risk of Cancer From Radiation Exposure During Parathyroid Imaging: Comparison of 4D CT and Parathyroid Scintigraphy.

OBJECTIVE The purpose of this study is to measure the organ doses and effective dose (ED) for parathyroid 4D CT and scintigraphy and to estimate the lifetime attributable risk of cancer incidence associated with imaging. MATERIALS AND METHODS Organ radiation doses for 4D CT and scintigraphy were measured on the basis of imaging with our institutions protocols. An anthropomorphic phantom with metal oxide semiconductor field effect transistor detectors was scanned to measure CT organ dose. Organ doses from the radionuclide were based on International Commission for Radiological Protection report 80. ED was calculated for 4D CT and scintigraphy and was used to estimate the lifetime attributable risk of cancer incidence for patients differing in age and sex with the approach established by the Biologic Effects of Ionizing Radiation VII report. A 55-year-old woman was selected as the standard patient according to the demographics of patients with primary hyperparathyroidism. RESULTS Organs receiving the highest radiation dose from 4D CT were the thyroid (150.6 mGy) and salivary glands (137.8 mGy). For scintigraphy, the highest organ doses were to the colon (41.5 mGy), gallbladder (39.8 mGy), and kidneys (32.3 mGy). The ED was 28 mSv for 4D CT, compared with 12 mSv for scintigraphy. In the exposed standard patient, the lifetime attributable risk for cancer incidence was 193 cancers/100,000 patients for 4D CT and 68 cancers/100,000 patients for scintigraphy. Given a baseline lifetime incidence of cancer of 46,300 cancers/100,000 patients, imaging results in an increase in lifetime incidence of cancer over baseline of 0.52% for 4D CT and 0.19% for scintigraphy. CONCLUSION The ED of 4D CT is more than double that of scintigraphy, but both studies cause negligible increases in lifetime risk of cancer. Clinicians should not allow concern for radiation-induced cancer to influence decisions regarding workup in older patients.

Comparison of Current and Past Surgical Smoke Control Practices

In 2010, we teamed with AORN to repeat a simple web-based survey on surgical smoke control practices first conducted in 2007. This survey of AORN members assessed the level of compliance with established surgical smoke control measures (ie, use of wall suction with an in-line particulate filter, use of a smoke evacuator, use of an N95 or other National Institute for Occupational Safety and Health-approved respirator) in various medical specialties and facilities throughout North America, as well as the extent to which compliance rates may have changed since 2007. Survey responses indicate that while the use of wall suction as a control measure has increased for nearly all procedures, progress in the adoption of other control measures has been mixed, with improvement for some procedures, no change for most procedures, and a decrease in compliance for a few procedures.

Quotient imaging with N‐ 13 L‐glutamate in osteogenic sarcoma: Correlation with tumor viability

An investigation was performed to correlate the regional uptake of N‐13 L‐glutamate with histologic changes in tumor tissue in patients undergoing adjuvant chemotherapy for osteogenic sarcoma. A parametric image was produced by calculating the ratio of N‐13 uptake in the tumor in a pixel‐by‐pixel fashion, using the presurgical scan as the numerator and the pretherapy scan as the denominator. The change in N‐13 uptake in 2 × 2‐cm regions of the tumor was compared with residual cell viability as determined by microscopic examination of multiple thin sections obtained from the surgical specimens. Regions that showed decreases in N‐13 uptake of more than 30% were frequently associated with areas of highly necrotic tumor, and regions that showed increasing uptake were associated with high residual cell viability and incomplete response to chemotherapy.

Imaging studies of patients with malignant fibrous histiocytoma using C-11-alpha-aminoisobutyric acid (AIB).

Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid which is rapidly transported into viable cells by the A-type or alanine-preferring amino acid transport system, has been labeled with the shortlived, positron-emitting radionuclide carbon-11. Carbon-11 labeled AIB is currently being evaluated as a tumor imaging agent for in vivo amino acid transport studies in patients with cancer. In this study, C-11 AIB was used to image two patients with malignant fibrous histiocytoma (MFH), a pleomorphic sarcoma. Following intravenous administration of C-11 AIB, tumors in the distal femur of one patient and in the anterior chest wall of another patient were well visualized using high energy gamma scintigraphy. Since therapy may alter the accumulation of amino acids in tumor tissue, studies using C-11 AIB in patients with MFH before and after chemotherapy are in progress.