Double-labeled metabolic maps of memory.

The physical changes representing a memory are believed to be localized to specific neurons, widely distributed in multiple parallel pathways in the brain. 2-Fluorodeoxyglucose, labeled with two discriminable radioactive tracers, was used to construct quantitative metabolic maps in split-brain cats during a visual task. One side of the brain served to estimate the metabolic variability of nonspecific influences. The other side was used to map metabolic changes related to the presence of previously learned visual cues, as well as changes related to nonspecific influences, in the same periods of time. When the two sides were compared, between 5 million and 100 million neurons (depending upon the significance level selected) were identified in which activity increased during presentation of the familiar cues. The wide distribution of these neurons throughout the brain is compatible with prior evidence of a distributed memory system. However, the large number of neurons involved is difficult to reconcile with theories in which individual neurons are dedicated to specific memories.

Regional myocardial substrate uptake in hypertensive rats: a quantitative autoradiographic measurement.

Severe hypertension causes global and regional changes in myocardial perfusion and substrate utilization. Regional perfusion and fatty acid utilization were evaluated by dual-tracer autoradiography in normotensive and hypertensive rats of the Dahl strain. The regional distributions of perfusion and fatty acid utilization were homogeneous in normotensive rats. Severe hypertension was associated with a homogeneous pattern of regional perfusion, but fatty acid utilization was focally decreased in the free wall of the left ventricle. The decrease in fatty acid uptake was associated with a concomitant increase in glucose utilization. These findings suggest that severe hypertension is associated with uniform myocardial perfusion and focal alterations in the substrates used for the performance of myocardial work.

Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: results from the first screening cycle (1998-2000).

CONTEXT: Due to the Chornobyl accident, millions were exposed to radioactive isotopes of iodine and some received appreciable iodine 131 (131I) doses. A subsequent increase in thyroid cancer has been largely attributed to this exposure, but evidence concerning autoimmune thyroiditis (AIT) remains inconclusive. OBJECTIVE: The objective of the study was to quantify risk of AIT after 131I exposure. DESIGN/SETTING/PARTICIPANTS: Baseline data were collected from the first screening cycle (1998-2000) of a large cohort of radiation-exposed individuals (n = 12,240), residents of contaminated, iodine-deficient territories of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and had thyroid radioactivity measurements made shortly after the accident. OUTCOMES: AIT was defined a priori based on various combinations of elevated antibodies to thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were considered to be an indicator of thyroid autoimmunity. RESULTS: No significant association was found between 131I thyroid dose estimates and AIT, but prevalence of elevated ATPO demonstrated a modest, significant association with 131I that was well described by several concave models. This relationship was apparent in individuals with moderately elevated ATPO and euthyroid, thyroid disease-free individuals. CONCLUSIONS: Twelve to 14 yr after the Chornobyl accident, no radiation-related increase in prevalence of AIT was found in a large cohort study, the first in which 131I thyroid doses were estimated using individual radioactivity measurements. However, a dose-response relationship with ATPO prevalence raises the possibility that clinically important changes may occur over time. Thus, further follow-up and analysis of prospective data in this cohort are necessary.

Normal organ radiation dosimetry and associated uncertainties in nuclear medicine, with emphasis on iodine-131.

In many medical applications involving the administration of iodine-131 ((131)I) in the form of iodide (I(-)), most of the dose is delivered to the thyroid gland. To reliably estimate the thyroid absorbed dose, the following data are required: the thyroid gland size (i.e. mass), the fractional uptake of (131)I by the thyroid, the spatial distribution of (131)I within the thyroid, and the length of time (131)I is retained in the thyroid before it is released back to blood, distributed in other organs and tissues, and excreted from the body. Estimation of absorbed dose to nonthyroid tissues likewise requires knowledge of the time course of activity in each organ. Such data are rarely available, however, and therefore dose calculations are generally based on reference models. The MIRD and ICRP have published metabolic models and have calculated absorbed doses per unit intake for many nuclides and radioactive pharmaceuticals. Given the activity taken into the body, one can use such models and make reasonable calculations for average organ doses. When normal retention and excretion pathways are altered, the baseline models need to be modified, and the resulting organ dose estimates are subject to larger errors. This paper describes the historical evolution of radioactive isotopes in medical diagnosis and therapy. We nonmathematically summarize the methods used in current practice to estimate absorbed dose and summarize some of the risk data that have emerged from medical studies of patients with special attention to dose and effects observed in those who received (131)I-iodide in diagnosis and/or therapy.

Intratumoral and whole-body distributions of C110 anti-carcinoembryonic antigen radioimmunotoxin after intraperitoneal and intravenous injection: a quantitative autoradiographic study.

The intratumoral and whole-body distributions of 90Y-labeled C110 anticarcinoembryonic antigen immunotoxin after i.p. and i.v. injection were compared by quantitative autoradiography. During in vitro incubation of spherical tumor nodules of LS174T human colon cancer (about 5 mm in diameter) in a medium containing C110 radioimmunotoxin (RIT), the direct penetration of the immunotoxin increased with time but was limited to the outer 300 microns of the tumor nodule after 12 h of incubation. In vivo experiments were performed in nude mice bearing LS174T xenografts as i.p. tumor nodules. Injection of C110 RIT i.p. resulted in a ring-like distribution, i.e., high uptake at the tumor periphery and considerably lower uptake at the tumor center (ratio of peripheral to central concentration, 7:1 at 1 day and 2:1 at 5 days). In contrast, i.v. injection provided a much smaller gradient in C110 RIT distribution from peripheral to central regions (ratio of peripheral to central concentration, 3:1 at 1 day and 1:1 at 5 days). Estimates of total tumor uptake of C110 RIT by quantitative autoradiography demonstrated almost equivalent tumor uptake after either i.p. or i.v. injection, while i.v. injection was associated with increased C110 RIT uptake in various normal organs, especially in the liver, as compared to i.p. injection. The results in this study suggest that (a) i.v. injection may produce more homogeneous distribution of C110 RIT in i.p. tumor nodules of LS174T but may also result in increased liver toxicity, and (b) i.p. injection may decrease C110 RIT exposure of normal tissues, which can reduce systemic toxicity, but may also produce more restricted intratumoral distribution of C110 RIT. In addition, current methods using a nude mouse model of i.p. tumor nodules and quantitative autoradiography allow us to assess intratumoral and whole-body distributions of radiolabeled immunoconjugates from various administration routes.

Preclinical assessments of 90Y-labeled C110 anti-carcinoembryonic antigen immunotoxin: a therapeutic immunoconjugate for human colon cancer.

We have synthesized 90Y-labeled immunotoxin (IT) containing ricin A chain and C110 anti-carcinoembryonic antigen monoclonal antibody (MAb) to produce a therapeutic immunoconjugate for human colon cancer. The C110 IT was labeled with 90Y via a benzylisothiocyanate derivative of diethylenetriaminepentaacetic acid. The efficiency of 90Y labeling was consistently 90 to 98%, with a specific activity of about 1 microCi/microgram. In in vitro stability studies, more than 80% of 90Y remained bound to the C110 IT for up to 5 days after incubation. The percentage of binding of 90Y-labeled C110 IT to carcinoembryonic antigen-coated microbeads was 86%, indicating good retention of the initial immunoreactivity of the C110 MAb. In in vitro protein synthesis inhibition assays, 90Y-labeled C110 IT was approximately 3.7-fold more toxic to the LS174T human colon carcinoma cell line than unmodified C110 IT and 1380-fold more toxic than 90Y-labeled C110 MAb. Biodistribution studies of 90Y-labeled C110 IT in LS174T tumor-bearing mice showed that, at 24 h following i.p. injection, high accumulation of radioactivity was seen in the i.p. tumor and liver and, thereafter, high accumulation in these tissues remained almost unchanged until up to 168 h, with percentage of injected dose/g ranging from 15 to 18% in the tumor and 10 to 15% in the liver. The radioactivity in the spleen and bone gradually increased with time and reached their highest levels (approximately 8% of injected dose/g) at 168 h. Estimation of absorbed radiation doses to the tissues showed that i.p. tumor would have received an approximately 1.5 to 7 times higher radiation dose than normal organs. In in vivo therapeutic trials, 90Y-labeled C110 IT provided survival prolongation of LS174T tumor-bearing mice superior to that with either unmodified C110 IT or 90Y-labeled C110 MAb (4 less than 0.01; Mann-Whitney U test). These results indicate that 90Y-labeled C110 anti-carcinoembryonic antigen IT may be a potent therapeutic immunoconjugate for human colon cancer and that it may have direct relevance for i.p. treatment of peritoneal carcinomatosis from colon cancers.

Pharmacokinetics in patients of an anti-carcinoembryonic antigen antibody radiolabeled with indium-111 using a novel diethylenetriamine pentaacetic acid chelator.

The pharmacokinetics of the C110 anti-carcinoembryonic antigen antibody radiolabeled with 111In via a novel benzylisothiocyanate derivative of diethylenetriamine pentaacetic acid have been determined in 12 patients. The chelator was attached to the protein via a thiourea bond and in such a way that all 5 carboxymethyl arms were presumably able to participate in chelation. Patients with known or suspected colorectal carcinoma received between 5 and 20 mg of the IgG antibody labeled with 5 mCi of 111In. Individual organ radioactivity levels were quantitated, and serum and urine samples were analyzed, principally by size exclusion high-performance liquid chromatography (HPLC). Total urinary excretion averaged 0.18% of the injected dose/h with large patient to patient variation. At early times postadministration (less than 8 h) the predominant radiolabeled species in urine was free diethylenetriamine pentaacetic acid most probably administered as a small radiocontaminant in the injectate. Thereafter, radioactivity in urine was primarily present as a low molecular weight catabolic product. Analysis of serum by size exclusion HPLC occasionally showed 3 radioactivity peaks, 2 of which are due to circulating immune complexes and labeled antibody. The third peak is of low molecular weight and is due to one or more products of antibody catabolism. Transchelation of 111In to circulating transferrin was observed but at modest levels. Quantitation of organ radioactivity showed that 18 +/- 4 (SD)% of the injected dose was in the liver at 1 day postadministration and 1.4 +/- 1.1 and 1.2 +/- 0.9% was in the spleen and in both kidneys, respectively, at this time. The mean half-life for clearance of total injected radioactivity was fitted to a single exponential and was found to be 34 h (SD, 14 h; N = 13) and that for antibody alone, assessed by size exclusion HPLC analysis of serum samples, was calculated to be 22 h (SD, 8 h; N = 10). Neither of these values nor organ radioactivity levels were affected by antibody-loading dose.

Intraperitoneal immunoconjugates.

Intracavitary instillation of radioantibodies has been proposed as therapy for anatomically confined malignant disease. To evaluate this therapeutic strategy, a monoclonal antibody reactive with human transferrin receptor (7D3) was evaluated for localization in a human malignant mesothelioma transplanted i.p. in athymic nude mice. This antibody was purified and labeled with 131I, 125I, or 111In. Radiolabeled antibody was administered i.p. or i.v. to tumor-bearing mice. Three h after injection, the percentage of injected dose/g (ID/g) of tumor was higher in free-floating ascites tumor cells (31.0%/g tumor cell pellet) after i.p. injection than after i.v. injection (12.0%). However, localization of radiolabel in i.p. solid tumors was similar (5.37% ID/g i.p. versus 4.73% of ID/g i.v.), and by 24 h both routes of administration produced similar localization of radiolabel in both free-floating ascites cells and solid tumors. In contrast, uptake of radiolabel into liver, kidney, and to a lesser extent bone and bone marrow, was less with i.p. than with i.v. administration. In clinical studies with 111In and 90Y antibodies administered i.p. to patients with ovarian cancer, confined biodistribution of the radioantibody was again seen, although interpatient variability of rate of egress of the radiolabel was documented. Therefore, both preclinical and clinical data indicate that i.p. therapy with immunoconjugates may be advantageous for cancer confined to the peritoneal cavity. This advantage stems primarily from reduced localization of isotope in organs of catabolism or toxicity (liver, kidney, bone, and bone marrow), rather than greatly increased levels of isotope in tumor. Unresolved problems include degree of antibody penetration into solid tumors, microdosimetry, and radioantibody effectiveness for tumor killing.

Quantitative whole-body autoradiography of radiolabeled antibody distribution in a xenografted human cancer model.

Quantitative whole-body autoradiography (WBAR) was used to study the biodistribution of goat anti-carcinoembryonic antigen and normal goat IgG, each labeled with 125I, in hamsters bearing the carcinoembryonic antigen-producing GW-39 human colonic carcinoma xenograft. Comparisons between computer-assisted videodensitometric profiles of WBARs and tissue radioactivity counts were made at 1, 3, and 7 days following administration of the radiolabeled IgGs. The results indicated that maximal tumor accretion of the radiolabeled antibody and normal IgG occurred within 1-3 days, with a marked selective accretion of antibody in the tumor being evidenced at 3-7 days because of clearance of normal IgG. Radioactivity derived from antibody IgG showed 6.5 to 118.7 times that found in other tissues, as measured by videodensitometry, whereas organ radioactivity counting revealed ratios of only 6.7 to 29.6. Specificity of tumor-cell accretion of the radiolabeled antibody was confirmed by microscopic autoradiography, showing intense labeling of the proliferating perimeters of GW-39 tumors. WBAR was found to have a resolution of 0.10 to 0.25 mm in 100-g hamsters, which appears to be greater than the resolving power of external body imaging by gamma camera scintigraphy. These studies suggest the use of WBAR and microautoradiography to complement external imaging methods for the analysis of antibody distribution and localization in cancer radioimmunodetection models.

Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma.

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

Initial clinical study of indium-111-labeled clone 110 anticarcinoembryonic antigen antibody in patients with colorectal cancer.

A murine monoclonal antibody directed against carcinoembryonic antigen (CEA) was labeled with indium-111 (111In) by means of a benzylisothiocyanate derivative of diethylenetriamine penta-acetic acid (DTPA) and used for clinical radioimmunodetection studies. Twenty-one patients having a history of surgically resected colorectal cancer and rising serum CEA levels suggestive of tumor recurrence were studied. Patients were infused over 20 minutes with 5, 10, or 20 mg of the monoclonal antibody labeled with 5 mCi of 111In. The mean radiochemical purity was greater than 96%. No toxicity was seen. The stability of the radiolabel on antibody in patient serum was demonstrated by high-performance liquid chromatography (HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with autoradiography, and immunoprecipitation for up to 96 hours after infusion. Tumor sites were identified in 20 of 21 patients. Sites of antibody accumulation in 20 patients were confirmed as tumor either by resection at laparotomy (16 patients) or fine-needle biopsy (four patients). Nine patients who had the identified lesion resected or irradiated showed return of the serum CEA antigen level to normal or near normal values. In the absence of high levels of circulating CEA (greater than 500 ng/mL), the disappearance of radioactivity from patient serum demonstrated first order elimination kinetics, with a mean half-life of 38 hours. The serum half-life was not affected by the dose of antibody administered or by serum CEA titers below 500 ng/mL. Despite a mean liver uptake of 18% injected dose (ID) 24 hours after administration, hepatic metastases were easily visualized as areas of increased uptake of radioactivity. Radioimmunodetection of recurrent colorectal cancer, not detected by computed tomographic (CT) scans, appears achievable with this agent. This may allow successful clinical intervention in selected patients.

Simultaneous emission and fluorescent scanning of the thyroid.

A comparison study of lithium-drifted silicon [Si(Li)] and high purity germanium (HpGe) was performed to explore the feasibility of replacing the current Si(Li) detector with the higher-efficiency HpGe detector. The improved efficiency of HpGe permits the use of collimators with higher resolution, which results in improved image quality over that achieved by the current Si(Li) system in use at Vanderbilt with an overall reduction in sensitivity of 29%. Since a 10 mm thick HpGe detector is about 75% efficient at 140 keV, the added advantage exists of simultaneously (a) imaging the stable-iodine distribution within the thyroid by x-ray fluorescence, and (b) the distribution of administered radiotracers such as [99mTc] pertechnetate. This comparison study shows that HpGe can compete with Si(Li) in overall detector efficiency, with the added benefits of better collimation to improve spatial resolution plus the simultaneous imaging of Tc-99m, all at the same equipment cost.

Evaluation of [iodine-125]N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3- propanediamine lung uptake using an isolated-perfused lung model.

Lung uptake of N,N,N'-trimethyl-N'-[2-Hydroxy-3-methyl-5-iodobenzyl]-1,3- propanediamine (HIPDM) has been reported, but the mechanism of this process has not yet been established. Thus, single-pass [125I]HIPDM accumulation was studied in rat lungs perfused with a Krebs-Ringer bicarbonate buffer containing 4.5% bovine albumin. Iodine-125 HIPDM lung accumulation was monitored by the percent of extraction per gram of lung tissue. Iodine-125 HIPDM lung uptake did not appear to occur by simple diffusion. As the time of perfusion was increased from 2 to 15 min, the rate of uptake of 2 microM [125I]HIPDM decreased by 40%. During a 2-min perfusion, 98.6% +/- 6.7 (n = 8) extraction was observed with 2 microM [125I]HIPDM, but only 38% +/- 2.0 (n = 3) was extracted when the [125I]HIPDM concentration was 1 mM. The addition of 1 mM chlorpromazine, propranolol or imipramine also decreased [125I]HIPDM lung uptake to 43.0% +/- 1.5, 51.4% +/- 2.2, and 49.8% +/- 0.8, respectively, (each n = 4 - 6, p less than 0.001). Cold (4 degrees C) had little effect on pulmonary accumulation (77.7% +/- 7.4, n = 5, p less than 0.01), and the addition of ouabain or the use of sodium-free medium had no effect. Thus, pulmonary [125I]HIPDM accumulation does not appear to occur by sodium-dependent active transport. Rather, its uptake appears to be similar to the uptake of other basic amines, such as propranolol and imipramine, which are known to bind by physico-chemical interactions to pulmonary endothelial cell membranes and reflect pulmonary vascular surface area.

Pancreas accumulation of radioiodinated HIPDM in mice and rats.

High pancreatic affinity for 131I-labeled HIPDM was observed in mice and rats. Although the brain uptake of [131I]HIPDM is very fast, the pancreatic uptake is rather slow. The pancreas to liver ratios (per gram) were 5.08 +/- 0.52 in mice and 5.15 +/- 0.65 in rats at 2 hr and 7.05 +/- 0.53 in mice and 8.06 +/- 1.14 in rats at 5 hr after administration. These ratios are higher than those obtained with routinely used pancreatic agent [75Se]selenomethionine. An increase in liver uptake and decrease in pancreatic uptake was observed at higher dose of carrier HIPDM, which resulted in lower pancreas to liver ratios. HIPDM is a new type of compound which shows predilection for pancreas. Our results suggest that [123I]HIPDM might be a useful agent for pancreas imaging.

Radiation absorbed dose from indium-111-CYT-356.

UNLABELLED: Indium-CYT-356 is an agent developed by CYTOGEN Inc. (CYT) (Princeton, NJ) for the use in staging patients with prostate cancer. This investigation was performed to provide the human dosimetry needed for Food and Drug Administration approval for routine use in patients. METHODS: Biodistribution data collected from three sites were obtained from prostate cancer patients who received diagnostic doses of 111In-CYT-356. Data included blood and urine collections, and the organ uptake value was measured from sequential conjugate whole-body and planar images over a 7-10 day period. Dose contributions from radioactivity in transit through the GI tract were estimated using a compartmental model. The calculations used the MIRD methodology and MIRDOSE 3. RESULTS: The total-body dose observed was 0.14 mGy/MBq, and the effective dose was found to be 0.25-0.29 mSv/MBq. The largest organ doses were found for the liver (1.0 mGy/MBq), kidneys (0.67 mGy/MBq) and spleen (0.88 mGy/MBq). CONCLUSION: The radiation dose to the patient from a typical 185 MBq administration of 111In-CYT-356 is comparable to the dose from other 111In-labeled whole antibodies used in the diagnosis and management of cancer patients. The inclusion of the GI tract as a source organ increases the effective dose by 18%.

Differentiation between malignant and benign solitary thyroid nodules by fluorescent scanning.

A quantitative fluorescent technique has been developed for making in vivo iodine content determinations of the total thyroid gland or of selected parts. In solitary thyroid nodules "cold" to radionuclide studies, the ratio of iodine content in the nodule to that in a corresponding area of the contralateral lobe has proven to be a good indicator of malignancy. In a preliminary study of 42 surgical patients, an iodine content ratio (ICR) below 0.60 (chosen a posteriori) proved to be an excellent indication of malignancy with a sensitivity of 100%, a specificity (predictive value) of 79%, and an overall accuracy of 90%. Further definitive studies are needed to verify these preliminary observations.

Quantitative autoradiography with radiopharmaceuticals, Part 1: Digital film-analysis system by videodensitometry: concise communication.

A simple low-cost digital film-analysis system using videodensitometry was developed to quantitate autoradiograms. It is based on a TV-film analysis system coupled to a minicomputer. Digital sampling of transmitted light intensities through the autoradiogram is performed with 8-bit gray levels according to the selected array size (128 X 128 to 1024 X 1024). The performance characteristics of the system provide sufficient stability, uniformity, linearity, and intensity response for use in quantitative analysis. Digital images of the autoradiograms are converted to radioactivity content, pixel by pixel, using step-wedge standards. This type of low-cost system can be installed on conventional mini-computers commonly used in modern nuclear medical facilities. Quantitative digital autoradiography can play an important role, with applications stretching from dosimetry calculations of radiopharmaceuticals to metabolic studies in conjunction with positron-emission tomography.

Count-rate variations with orientation of camera detector.

Variations of count rate with orientation of the detector were investigated. Scaled difference images (SDI) were generated from pairs of arrays acquired at different detector orientations. The hypothesis tested was that any variations could be totally explained by random disintegration noise. We accepted or rejected this hypothesis according to the statistical significance of the difference between the measured and theoretical means and variances of the SDIs. When two images acquired at the same angle were compared, no significant differences were noted. Differences were significant between most pairs of images obtained at different angular orientations. Cameras with inadequate magnetic shielding were more sensitive to orientation effects than those with proper magnetic shielding. The mode of variation strongly suggests an interaction with a magnetic field.

Detection of cardiomyopathy in an animal model using quantitative autoradiography.

A fatty acid analog (15-p-iodophenyl)-3,3 dimethyl-pentadecanoic acid (DMIPP) was studied in cardiomyopathic (CM) and normal age-matched Syrian hamsters. Dual tracer quantitative wholebody autoradiography (QARG) with DMIPP and 2-[14C(U)]-2-deoxy-2-fluoro-D-glucose (FDG) or with FDG and 201Tl enabled comparison of the uptake of a fatty acid and a glucose analog with the blood flow. These comparisons were carried out at the onset and mid-stage of the disease before congestive failure developed. Groups of CM and normal animals were treated with verapamil from the age of 26 days, before the onset of the disease for 41 days. In CM hearts, areas of decreased DMIPP uptake were seen. These areas were much larger than the decrease in uptake of FDG or 201Tl. In early CM only minimal changes in FDG or 201Tl uptake were observed as compared to controls. Treatment of CM-prone animals with verapamil prevented any changes in DMIPP, FDG, or 201Tl uptake. DMIPP seems to be a more sensitive indicator of early cardiomyopathic changes as compared to 201Tl or FDG. The trial of DMIPP and SPECT in the diagnosis of human disease, as well as for monitoring the effects of drugs which may prevent it seems to be warranted.