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Important progress has been made over the last decade in the classification, imaging, and treatment of neuroendocrine neoplasm (NENs), with several new agents approved for use. Although the treatment options available for patients with well-differentiated neuroendocrine tumors (NETs) have greatly expanded, the rapidly changing landscape has presented several unanswered questions about how best to optimize, sequence, and individualize therapy. Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of gastroenteropancreatic-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included 1) PRRT re-treatment, 2) PRRT and immunotherapy combinations, 3) PRRT and DNA damage repair inhibitor combinations, 4) treatment for liver-dominant disease, 5) treatment for PRRT-resistant disease, and 6) dosimetry-modified PRRT., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: This practice parameter (PP) for Lutetium-177 (Lu-177) DOTATATE peptide receptor radionuclide therapy (PRRT) aims to guide authorized users in selection of appropriate adult candidates with gastroeneropancreatic neuroendocrine tumors (GEP-NETs) from foregut, midgut, and hindgut. The essential selection criteria include somatostatin receptor-positive GEP-NETs, which are usually inoperable and progressed despite standard therapy. Lu-177 DOTATATE is a radiopharmaceutical with high avidity for somatostatin receptors that are overexpressed by these tumors. This document ensures safe handling of Lu-177 DOTATATE by the authorized users and safe management of affected patients., Methods: The document was developed according to the systematic process developed by the American College of Radiology (ACR) and described on the ACR Web site (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards). The PP development was led by 2 ACR Committees on Practice Parameters (Nuclear Medicine and Molecular Imaging and Radiation Oncology) collaboratively with the American College of Nuclear Medicine, American Society of Radiation Oncology, and Society of Nuclear Medicine and Molecular Imaging., Results: The Lu-177 DOTATATE PP reviewed pharmacology, indications, adverse effects, personnel qualifications, and required clinical evaluation before starting the treatment, as well as the recommended posttherapy monitoring, quality assurance, documentation, and appropriate radiation safety instructions provided in written form and explained to the patients., Conclusions: Lu-177 DOTATATE is available for therapy of inoperable and/or advanced GEP-NETs when conventional therapy had failed. It can reduce tumor size, improve symptoms, and increase the progression free survival. The PP document provides clinical guidance for authorized users to assure an appropriate, consistent, and safe practice of Lu-177 DOTATATE., Competing Interests: Conflicts of interest and sources of funding: N.B.D. reports a grant from Boston Scientific, consulting fees from Boston Scientific, and honoraria from MedLearning. L.B. reports a grant from AAA Novartis, and participation on an advisory board for AAA Novartis. R.K.J.B. reports participation on an advisory board for Covera Health. E.C.G. reports consulting fees from Advanced Accelerator Applications. R.F.H. reports funding from National Institutes of Health/National Cancer Institute, and a leadership role as Chairman of the Radiopharmaceutical Therapy Subcommittee of the American Association of Physicists in Medicine. T.A.H. reports grants or contracts from Philips and Clovis Oncology, consulting fees from Curium and ITM, and participation on advisory boards for Ipsen and Blue Earth Diagnostics. D.A.P. reports grants from Siemens, Nordic Nanovector, Progenics, and 511 Pharma, and consulting fees from Siemens, 511 Pharma, Progenics, Actinium, and Ipsen. B.S.-B. reports a grant from Blue Earth Diagnostics, honoraria from PETNET and Blue Earth Diagnostics, and a leadership role as Society of Nuclear Medicine and Molecular Imaging (SNMMI) co-chair of outreach committee secretary of American College of Nuclear Medicine, Central Chapter SNMMI, and Academic Council SNMMI. R.M.S. reports a grant from Endocyte Inc. For the remaining authors, none were declared., (Copyright © 2022 Clinical Nuclear Medicine and American Journal of Clinical Oncology.)

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for metastatic neuroendocrine tumors. Delivering a sufficient tumor radiation dose remains challenging because of critical-organ dose limitations. Adding 131 I-metaiodobenzylguanidine ( 131 I-MIBG) to PRRT may be advantageous in this regard. Methods: A phase 1 clinical trial was initiated for patients with nonoperable progressive neuroendocrine tumors using a combination of 90 Y-DOTATOC plus 131 I-MIBG. Treatment cohorts were defined by radiation dose limits to the kidneys and the bone marrow. Subject-specific dosimetry was used to determine the administered activity levels. Results: The first cohort treated subjects to a dose limit of 1,900 cGy to the kidneys and 150 cGy to the marrow. No dose-limiting toxicities were observed. Tumor dosimetry estimates demonstrated an expected dose increase of 34%-83% using combination therapy as opposed to 90 Y-DOTATOC PRRT alone. Conclusion: These findings demonstrate the feasibility of using organ dose for a phase 1 escalation design and suggest the safety of using 90 Y-DOTATOC and 131 I-MIBG., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

We report the impact of 177 Lu DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors (NETs) often find burdensome. Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial ( 177 Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures. Results: Patients (intent-to-treat) who received 177 Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For 177 Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 days per 4 weeks, respectively, compared with 0.99, 1.44, and 2.54 days for high-dose octreotide LAR. The mean differences were 3.11 days (95% confidence interval, 1.35-4.88; P = 0.0007) for abdominal pain, 3.11 days (1.18-5.04; P = 0.0017) for diarrhea, and 1.98 days (0.08-3.88; P = 0.0413) for flushing, favoring 177 Lu-DOTATATE. A positive repeated measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. Conclusion: In addition to efficacy and quality of life benefits, symptom diaries from NETTER-1 demonstrated that treatment with 177 Lu DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut NETs, compared with high-dose octreotide LAR, supporting a beneficial effect of 177 Lu DOTATATE on HRQoL., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Peptide receptor radionuclide therapy (PRRT) is an effective form of treatment of patients with metastatic neuroendocrine tumors, delivering modest objective tumor response rates but notable survival and symptomatic benefits. The first PRRT approved by the US Food and Drug Administration was lutetium 177-DOTATATE and is for use in adults with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. The treatment paradigm typically leads to significant improvement in symptomology coupled with an extended period of progression-free survival. Side effects are limited, with a small fraction of individuals experiencing clinically significant long-term renal or hematologic toxicity., (Published by Elsevier Inc.)

With the recent approval of 177 Lu-DOTATATE for use in gastroenteropancreatic neuroendocrine tumors, access to peptide receptor radionuclide therapy is increasing. Representatives from the North American Neuroendocrine Tumor Society and the Society of Nuclear Medicine and Molecular Imaging collaborated to develop a practical consensus guideline for the administration of 177 Lu-DOTATATE. In this paper, we discuss patient screening, maintenance somatostatin analog therapy requirements, treatment location and room preparation, drug administration, and patient release as well as strategies for radiation safety, toxicity monitoring, management of potential complications, and follow-up. Controversies regarding the role of radiation dosimetry are discussed as well. This document is designed to provide practical guidance on how to safely treat patients with this therapy., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Pretherapy PET with 86 Y-DOTATOC is considered the ideal dosimetry protocol for 90 Y-DOTATOC therapy; however, its cost, limited availability, and need for infusion of amino acids to mimic the therapy administration limit its use in the clinical setting. The goal of this study was to develop a dosimetric method for 90 Y-DOTATOC using 90 Y-DOTATOC PET/CT and bremsstrahlung SPECT/CT and to determine whether dosimetry-based administered activities differ significantly from standard administered activities. Methods: This was a prospective phase 2 trial of 90 Y-DOTATOC therapy in patients with somatostatin receptor-positive tumors. 90 Y-DOTATOC was given in 3 cycles 6-8 wk apart. In the first cycle of therapy, adults received 4.4 GBq and children received 1.85 GBq/m 2 ; the subsequent administered activities were adjusted according to the dosimetry of the preceding cycle so as not to exceed a total kidney dose of 23 Gy and bone marrow dose of 2 Gy. The radiation dose to the kidneys was determined from serial imaging sessions consisting of time-of-flight 90 Y-DOTATOC PET/CT at 5 h after therapy and 90 Y-DOTATOC bremsstrahlung SPECT/CT at 6, 24, 48, and 72 h. The PET/CT data were used to measure the absolute concentration of 90 Y-DOTATOC and to calibrate the bremsstrahlung SPECT kidney clearance data. The radiation dose to the kidneys was determined by multiplying the time-integrated activity (from the fitted biexponential curve of renal clearance of 90 Y-DOTATOC) with the energy emitted per decay, divided by the mass of the kidneys. Results: The radiation dose to the kidneys per cycle of 90 Y-DOTATOC therapy was highly variable among patients, ranging from 0.32 to 3.0 mGy/MBq. In 17 (85%) of the 20 adult patients who received the second and the third treatment cycles of 90 Y-DOTATOC, the administered activity was modified by at least 20% from the starting administered activity. Conclusion: Renal dosimetry of 90 Y-DOTATOC is feasible using 90 Y-DOTATOC time-of-flight PET/CT and bremsstrahlung SPECT/CT and has a significant impact on the administered activity in treatment cycles., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Localization of the site of the unknown primary tumor is critical for surgical treatment of patients presenting with neuroendocrine tumor (NET) with metastases. Methods: Forty patients with metastatic NET and unknown primary site underwent 68 Ga-DOTATOC PET/CT in a single-site prospective study. The 68 Ga-DOTATOC PET/CT was considered true-positive if the positive primary site was confirmed by histology or follow-up imaging. The scan was considered false-positive if no primary lesion was found corresponding to the 68 Ga-DOTATOC-positive site. All negative scans for primary tumor were considered false-negative. A scan was classified unconfirmed if 68 Ga-DOTATOC PET/CT suggested a primary, however, no histology was obtained and imaging follow-up was not confirmatory. Results: The true-positive, false-positive, false-negative, and unconfirmed rates for unknown primary tumor were 38%, 7%, 50%, and 5%, respectively. Conclusion: 68 Ga-DOTATOC PET/CT is an effective modality in the localization of unknown primary in patients with metastatic NET., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: The objective of this study was to describe the outcomes of patients in the University of Iowa Neuroendocrine Tumor (NET) Database treated with peptide receptor radionuclide therapy (PRRT)., Methods: One hundred thirty-five patients from the University of Iowa NET Database who received PRRT were analyzed, their characteristics were described, and survival was calculated., Results: The median age at diagnosis was 51 years, and 64% were men. The primary tumor was located in the small bowel (SBNET) in 37.8%, in the pancreas (PNET) in 26.0%, in the lung in 13.3%, in unknown primary in 9.6%, and in other sites in 13.3%. A radiographic response of any magnitude was observed in 65.8%, 11.1% had a mixed response, and 15.4% showed progression. The overall survival (OS) from the first PRRT was 40 months, and the median time to progression was 23.9 months. Higher pretreatment chromogranin A and pancreastatin levels predicted inferior OS., Conclusions: Peptide receptor radionuclide therapy resulted in a relatively long OS and time to progression in heavily pretreated North American patients with advanced NETs. Elevated pretreatment chromogranin A and pancreastatin predicted shorter OS after therapy. Peptide receptor radionuclide therapy is a valuable treatment option in patients with advanced NETs, especially SBNETS.

Background: Peptide receptor radionuclide therapy (PRRT) is an effective form of treatment for patients with metastatic neuroendocrine tumors (NETs). However, delivering sufficient radiation dose to the tumor to result in a high percentage of long-term tumor remissions remains challenging because of the limits imposed on administered activity levels by radiation damage to normal tissues. The goal of this study was to evaluate the dosimetric advantages of adding (131)I meta-iodobenzylguanidine ((131)I-MIBG) to (90)Y DOTA Phe1-Tyr3-octreotide ((90)Y-DOTATOC) in patients with advanced stage midgut NETs., Methods: Ten patients were imaged simultaneously with (131)I-MIBG and (111)In-pentetreotide (as a surrogate for (90)Y-DOTATOC) on days 1, 2, and 3 post-administration. Blood samples were obtained at the same time points. Using dosimetry measures from this data and our previously published methodology for calculating optimal combined administered activity levels for therapy, we determined the amount of (131)I-MIBG that could be added to (90)Y-DOTATOC without exceeding normal organ dose limits (marrow and kidneys) along with the expected increase in associated tumor dose, if any., Results: We found that a median value of 34.6 GBq of (131)I-MIBG could be safely added to (90)Y-DOTATOC (delivered over multiple cycles) by reducing the maximum total deliverable (90)Y-DOTATOC by a median value of 24.5%. Taking this treatment approach, we found that there would be a median increase in deliverable tumor dose of 4,046 cGy in six of the ten subjects. Of note, there were a small number of metastases that were positive for only one or the other of these radiopharmaceuticals within the same subject., Conclusions: We conclude that approximately half of the patients with midgut NETs that are eligible for PRRT could reasonably be expected to benefit from the addition of (131)I-MIBG to (90)Y-DOTATOC.

Objective: To evaluate the repeatability of gallium-68 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA)-D-Phe1-Try3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) in neuroendocrine tumors., Methods: Five patients with neuroendocrine tumors were imaged with 68Ga-DOTATOC PET twice within 5 days. Maximum and mean standardized uptake values (SUVmax and SUVmean) and kinetic parameters (K-Patlak and K-influx) of target lesions were measured. The repeatability of these measurements was investigated., Results: Forty-seven target lesions were identified on whole-body PET and 21 lesions on dynamic images. There was excellent repeatability with intraclass correlation coefficient of 0.99 for SUVmax, SUVmean, and K-Patlak, and 0.85 for K-influx. The median absolute percent differences and the interquartile ranges (IQR) between 2 scans for SUVmax and SUVmean were 7.4% (IQR, 14.1%) and 9.3% (IQR, 10.6%), respectively. The median absolute percent differences for K-Patlak and K-influx were 12.5% (IQR, 12.6%) and 29.9% (IQR, 22.4%), respectively. The SUVmax of target lesions did not differ by more than 25% between the 2 scans., Conclusions: 68Ga-DOTATOC PET imaging of neuroendocrine tumors is highly reproducible. A difference of more than 25% in SUVmax represents a change that is larger than the measurement error observed on repeated studies and should reflect a significant change in the biological character of the tumor.

Several diagnostic imaging techniques have been used successfully for evaluating patients with neuroendocrine tumors (NETs). These techniques include computed tomography (CT), magnetic resonance imaging, positron emission tomography/CT, single-photon emission CT (SPECT), and SPECT/CT. This article reviews the various imaging methods and their respective advantages and limitations for use in different types of NETs, in particular carcinoid tumors., (Published by Elsevier Inc.)

Well-differentiated neuroendocrine tumors (NETs) of the jejunum, ileum, and appendix are also collectively known as midgut carcinoids. Similar to NETs in general, the diagnosed incidence of the midgut NETs is on the rise. Their presenting symptoms vary depending on stage and primary site. Local-regional NETs often present with vague and nonspecific symptoms. Classic carcinoid syndrome is more likely to appear in patients with advanced disease. Local-regional NETs of the small bowel should be resected whenever possible. With the exception of small well-differentiated NETs of the appendix, NETs of the midgut have substantial risk of relapse after resection and need to be followed for at least 7 years.Metastatic/advanced NETs of the midgut are incurable. Optimal management requires a multidisciplinary approach. Somatostatin analogs are effective in the management of carcinoid syndrome. Octreotide long-acting release has also recently been shown to delay disease progression. Liver-directed therapy and surgical debulking can improve quality of life in selected patients. Pivotal phase 3 studies with bevacizumab targeting vascular endothelial growth factor and everolimus targeting mTOR (mammalian target of rapamycin) are ongoing and may lead to improved outcome. Further studies of novel approaches such as peptide receptor radiotherapy are also warranted.

Well-differentiated neuroendocrine tumors (NETs) of the stomach and pancreas represent 2 major subtypes of gastrointestinal NETs. Historically, there has been little consensus on the classification and management of patients with these tumor subtypes. We provide an overview of well-differentiated NETs of the stomach and pancreas and describe consensus guidelines for the treatment of patients with these malignancies.

In this paper, we investigate a previously proposed mathematical model describing the effects that an innovative combined radiopharmaceutical therapy might have on the delivery of radiation to the tumor and limiting critical organs. While focused on a specific dual agent therapy, this investigation will prove mathematically that for any two therapeutic radiopharmaceuticals with different limiting critical organs the model provides patient specific conditions under which combination therapy is superior to single agent therapy. In addition, this paper outlines general methods for calculating the amounts of administered radioactivity for each drug required to optimize tumor radiation dose. We also consider extensions of this model to include an arbitrary number of independent radiopharmaceuticals and/or other treatment factors.

Background: Samarium Sm 153 lexidronam (Sm-153) is an effective and well-tolerated treatment for painful bone metastases. The purpose of the analysis was to assess the safety and efficacy of repeated doses of Sm-153 in patients with metastatic bone pain., Methods: Data were collected prospectively for 202 patients administered 1.0 mCi/kg of Sm-153. Particular emphasis was placed on analysis of data from 55 patients receiving > or = 2 doses. Pain scores, adverse events, and hematologic parameters were assessed after each dose., Results: Mild, transient suppression of platelets and white blood cell counts was the most common adverse event after treatment. Nadirs were approximately half of baseline at 4 weeks after dosing with recovery by Week 8 in 90% of patients. Temporary grade 3 thrombocytopenia occurred in 11%, 12%, and 17% of patients after the first, second, and third drug administration, respectively. Grade 3 leukopenia occurred in less than 7% of patients independent of the number of administrations. Significant decreases in pain scores (P < .001) were observed at Week 4 after each of the first 3 doses and maintained at Week 8 after the first 2 doses (P < .003) but not the third. Decreases in pain scores were observed in 70%, 63%, and 80% of patients, respectively, at Week 4 after the first 3 administrations., Conclusions: Repeated dosing of 1.0 mCi/kg of Sm-153 was both safe and effective and is a reasonable treatment option in patients whose bone pain responds and then recurs after an initial dose provided that adequate hematologic function is present at the time of drug administration., ((c) 2007 American Cancer Society.)

Unlabelled: (131)I-Metaiodobenzylguanidine (MIBG) and (90)Y-DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) have been used as radiotherapeutic agents for treating neuroendocrine tumors. The tumor dose delivered by these agents is often insufficient to control or cure the disease. However, these 2 agents used together could potentially increase tumor dose without exceeding the critical organ dose because the dose-limiting tissues are different. In this paper, we investigate the conditions in which combined-agent therapy is advantageous and we quantify the expected tumor-dose gain., Methods: A series of equations was derived that predicted the optimal combination of agents and the fractional increase in tumor dose available from combined-agent therapy with respect to either (131)I-MIBG or (90)Y-DOTATOC. The results obtained from these derivations were compared with direct dose calculations using published dosimetric organ values for (131)I-MIBG and (90)Y-DOTATOC along with critical organ-dose limits. Tumor dose was calculated as a function of the tumor-dose ratio, defined as the (90)Y-DOTATOC tumor dose per megabecquerel divided by the (131)I-MIBG tumor dose per megabecquerel. Comparisons were made between the dose delivered to tumor with single-agent therapy and the dose delivered to tumor with combined-agent therapy as a function of the tumor-dose ratio and the fraction of activity contributed by each agent., Results: The dose model accurately predicted the optimal combination of agents, the range at which combined-agent therapy was advantageous, and the magnitude of the increase. For the published organ dosimetry and critical organ-dose limits, combined-agent therapy increased tumor dose when the tumor-dose ratio was greater than 0.67 and less than 5.93. The maximum combined-agent tumor-dose increase of 68% occurred for a tumor-dose ratio of 2.57, using 92% of the maximum tolerated (90)Y-DOTATOC activity supplemented with 76% of the maximum tolerated activity of (131)I-MIBG. Variations in organ dose per megabecquerel and dose-limiting values altered both the magnitude of the increase and the range at which combined-agent therapy was advantageous., Conclusion: Combining (131)I-MIBG and (90)Y-DOTATOC for radiotherapy of neuroendocrine tumors can significantly increase the delivered tumor dose over the dose obtained from using either agent alone. Prior knowledge of the normal-organ and tumor dosimetry of both agents is required to determine the magnitude of the increase.

Background: Coronary artery disease impairs cardiac vasodilatory reserve. A low ratio of cardiac to hepatic vasodilatory reserve may be diagnostic for coronary artery disease., Aim: To compare the ratio of cardiac to hepatic uptake of 99mTc-tetrofosmin during adenosine infusion and at rest in patients with and without coronary artery disease in order to determine whether the ratio was significantly different between the two groups., Methods: Fifty-one patients who underwent coronary angiography and adenosine stress myocardial perfusion imaging using 99mTc-tetrofosmin were studied retrospectively. Anterior planar images from the single photon emission computed tomography (SPECT) raw data were used to draw regions of interest around the heart and liver. The counts per pixel in each region were used to calculate the stress ratio (SR) and the rest ratio (RR) as follows: SR = (cardiac counts per pixel)at stress/(hepatic counts per pixel)at stress; RR = (cardiac counts per pixel)at rest/(hepatic counts per pixel)at rest. The SR and SR/RR ratios were compared in patients with and without significant coronary artery disease. Receiver operating characteristic curves were drawn for SR and SR/RR., Results: The SR and SR/RR ratios were significantly lower in patients with significant coronary artery disease than in patients without (P<0.001). A cut-off ratio of SR/RR = 1.00 yielded 87% sensitivity and 74% specificity for the detection of significant coronary artery disease. Combining SR/RR with standard SPECT image interpretation increased the sensitivity without substantially changing the specificity in comparison with standard SPECT image interpretation only., Conclusion: Comparison of cardiac to hepatic 99mTc-tetrofosmin concentration at rest and under adenosine stress provides useful diagnostic information for the assessment of the presence of significant coronary artery disease.

Background: 99mTc-depreotide (NeoTect) is a synthetic somatostatin analogue, which binds to somatostatin receptor (SSTR) subtypes 2, 3 and 5. Imaging patients with non-Hodgkin's lymphoma (NHL) using the somatostatin analogue In-pentetreotide (Octreoscan) has demonstrated the feasibility of identifying lymphoma sites with this class of peptide radiopharmaceutical. SSTR peptides can be labelled with beta emitters and, if sufficient tumour uptake relative to normal organs can be demonstrated, therapeutic applications can be considered., Methods: In this prospective Institutional Review Board (IRB)-approved study, patients with NHL and a recent computed tomography (CT) examination were eligible. Whole-body and selected single-photon emission computed tomography (SPECT) imaging was performed 1 h after intravenous injection of 99mTc-depreotide. Images were compared with CT scan findings. The radioactivity concentration of 99mTc-depreotide in abdominal/pelvic tumour sites, together with normal organs, was determined and expressed as the percentage of injected activity per gram of tissue (%IA x g)., Results: Paired CT and 99mTc-depreotide images for three patients with indolent and six with aggressive NHL revealed abnormal 99mTc-depreotide uptake corresponding to the tumour seen on CT in seven of these patients. In three of the patients, all known tumour sites were detected on 99mTc-depreotide images. The mean %IA x g for nine abdominal/pelvic tumour foci from four patients was found to be 0.004% (range, 0.001-0.007%). The mean tumour to bone marrow activity concentration ratio in these four patients was found to be 0.94 (range, 0.33-1.40), whereas the tumour to kidney ratio was 0.53 (range, 0.16-0.80)., Conclusions: Levels of 99mTc-depreotide in tumour suggest at least the possibility of potential therapy with beta emitter-labelled SSTR peptides; however, depreotide itself appears not to be a suitable candidate as a targeting agent due to the relatively high bone marrow concentration.

Background: Few fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) nonsmall cell lung cancer (NSCLC) trials have had sufficient patients to adequately evaluate PET for mediastinal staging. We question whether once PET is performed, is mediastinoscopy necessary?, Methods: We performed a 5-year retrospective analysis of operable patients with known or suspicious NSCLC. Standard PET techniques were used. Inclusion criteria were (1) surgical mediastinal nodal sampling by mediastinoscopy within 31 days of the PET and (2) definitive diagnosis., Results: There were 237 patients who met the evaluation criteria; ninety-nine patients with NSCLC and 138 with suspicious lesions (137 men and 100 women; aged 20 to 88 years). The PETs were performed from 0 to 29 days before mediastinoscopy (median, 7 days). The standardized uptake value for the primary lesion was 0 to 24.6 (7.9+/-5.0). Nine primary lesions had no FDG uptake (1 benign, 8 NSCLCs). Seventy-one patients (31%) had mediastinal PET positive disease, and 44 patients (19%) had histologic positive mediastinal disease; N2 41 patients (17%) and N3 9 patients (4%). In 6 patients (3%), the initial frozen sections were negative, but PET positivity encouraged further biopsies that were positive for cancer. The PET sensitivity was 82%, specificity 82%, accuracy 82%, negative predictive value 95%, and positive predictive value was 51%. All primary lesions with a standardized uptake value less than 2.5 and a negative mediastinal PET were negative histologically (n = 29). Logistic regression analysis resulted in 100% specificity for PET in this group., Conclusions: In NSCLC PET may reduce the necessity for mediastinoscopy when the primary lesion standardized uptake value is less than 2.5 and the mediastinum is PET negative. Accepting this approach in our patient population, the need for mediastinoscopy would have been reduced by 12%.

Objective: Standard uptake values (SUVs) are widely used for quantifying the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours. The objective of this study was to evaluate the accuracy of SUVs for malignancy in lung nodules/masses and to analyse the effects of tumour size, blood glucose levels and different body weight corrections on SUV., Methods: One hundred and twenty-seven patients with suspicious lung lesions imaged with 18F-FDG positron emission tomography (PET) were studied retrospectively. Pathology results were used to establish lesion diagnosis in all cases. SUVs based on maximum pixel values were obtained by placing regions of interest around the focus of abnormal 18F-FDG uptake in the lungs. The SUVs were calculated using the following normalizations: body weight (BW), lean body weight (LBW), scaled body surface area (BSA), blood glucose level (Glu) and tumour size (Tsize). Receivers operating characteristic (ROC) curves were generated to compare the accuracy of different methods of SUV calculation., Results: The areas under the ROC curves for SUV(BW), SUV(BW+Glu), SUV(LBW), SUV(LBW+Glu), SUV(BSA), SUV(BSA+Glu) and SUV(BW+Tsize) were 0.915, 0.912, 0.911, 0.912, 0.916, 0.909 and 0.864, respectively., Conclusion: The accuracy of SUV analysis for malignancy in lung nodules/masses is not improved by correction for blood glucose or tumour size or by normalizing for body surface area or lean body weight instead of body weight.

A patient with stage D3 prostate cancer was given 11 separate doses of samarium-153 lexidronam (Sm-153 ethylenediaminetetramethylene phosphonate) of 1 mCi/kg (37 MBq/kg) in a period of 28 months for bone pain from metastases. With the first five doses, Sm-153 lexidronam clearly reduced his bone pain and improved his quality of life, as determined by pain-assessment scores and the patient's self-assessment of its effect on his ability to perform activities of daily living. With doses 6 through 11, pain at baseline was on average less, and as a result beneficial effects after treatment were not as apparent. Samarium-153 lexidronam produced transient decreases in the leukocyte and platelet counts, but these never became low enough to cause clinical concern. This case shows both the efficacy and the safety of Sm-153 lexidronam in repeated treatments for metastatic bone pain in patients with prostate cancer.

Following androgen ablation therapy, skeletal metastases from prostate cancer appear in some instances to show an increase in 99Tcm-methylene diphosphonate (99Tcm-MDP) uptake. Such a phenomenon could represent a mechanism to increase delivery of bone-seeking therapeutic agents to skeletal metastatic sites. The aim of this study was to characterize more precisely the potential increase in 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone therapy. Baseline bone scans were performed within 1 week of onset of hormone therapy in patients with stage D2 prostate cancer followed by multiple repeat bone scans for up to 4-6 weeks. The count density within metastatic lesions was divided by the average count density from several areas of normal bone to obtain a lesion to normal bone uptake ratio (L/N) for each lesion in each scan. Altogether, 61 skeletal metastases were identified on bone scans from five subjects. Eighty-four percent (51/61) of these lesions showed an increase in 99Tcm-MDP activity relative to normal bone following initiation of hormone therapy with a mean peak increase of 39%. Thirty-nine of these 51 metastatic lesions showed maximum uptake at 3 weeks post-onset of hormone treatment. From our findings, it appears that approximately 3 weeks following initiation of hormone blockade, most skeletal metastases from prostate cancer will demonstrate significantly enhanced 99Tcm uptake relative to normal bone. Consequently, it may be possible to improve the uptake and effectiveness of therapeutic bone-seeking radiopharmaceuticals by administering these agents following hormone therapy in patients with prostate cancer metastases.

Background: To determine the relative utility of positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging with Combidex (MRI-C) in the non-invasive staging of non-small cell lung cancer (NSCLC) mediastinal lymph nodes (MLN), we compared the three tests' individual performance with surgical mediastinal sampling. In contrast to prior studies, cytology was not used., Methods: The MLN were evaluated using PET and CT in 64 NSCLC patients. MRI-C was performed in 9 of these patients. MLN with a PET standard uptake value greater than or equal to 2.5, or greater than 1 cm in the short axis by CT or lack of MRI-C signal change were considered positive for metastatic disease. All MLN were sampled and subjected to standard pathologic analysis. PET, CT, and MRI-C scans were interpreted blinded to the histopathological results. Sensitivity, specificity, and accuracy for each scan type to appropriately stage MLN was determined using pathologic results as the standard., Results: Thirty patients had stage I disease, 8 stage II, 9 stage IIIA, 7 stage IIIB, and 10 stage IV. Two-hundred-and-thirty MLN were sampled. Sixteen patients had metastatic mediastinal disease. Compared to the pathological results, PET, CT, and MRI-C had a sensitivity, specificity, and accuracy of 70%, 86%, 84%; 65%, 79%, 76%; 86%, 82%, and 83%, respectively. PET and MRI-C were statistically more accurate than CT (p<0.001). In cases where PET and CT did not identify MLN involvement with NSCLC, 8% (2/25) were pathologically positive., Conclusions: PET and MRI-C are statistically more accurate than CT. However, the differences are small and may not be clinically relevant. No technique was sensitive or specific enough to change the current recommendation to perform mediastinoscopy for MLN staging in NSCLC.

The present case study describes the neurobehavioural, neurodiagnostic, and positron emission tomography (PET) scan findings in a child who sustained a whiplash-type injury in a motor vehicle accident. Although neck and back pain were reported immediately, neurobehavioural symptoms, such as staring spells, gradually increased in frequency over a 2-year period following the accident. At 4 years after the accident the patient's symptoms persisted, as reported by teachers and parents, and more extensive diagnostic work-up was initiated. Standard EEG was normal while two ambulatory EEGs were abnormal and interpreted as epileptiform. A PET scan showed evidence of marked hypometabolism in both temporal lobes. Neuropsychological findings were consistent with PET findings and reflected verbal and visual memory deficits in the context of high average intelligence. Treatment with carbamazepine, verapamil, and fluoxetine greatly improved the patient's symptoms. The present case illustrates an example of a poor outcome in a paediatric case of mild traumatic brain injury, the importance of PET in demonstrating definitive evidence of brain dysfunction, and the child's positive response to anticonvulsant medication.

The exercise 201T1 imaging procedure in patients with left bundle branch block (LBBB) is associated with a relatively high frequency of false-positive septal perfusion defects. We therefore initiated a study designed to determine the frequency of false-positive septal defects seen with adenosine/thallium imaging. In total, 900 adenosine/thallium cases performed at our institution for assessment of coronary artery disease were reviewed. Sixty-eight patients had LBBB on resting electrocardiogram (ECG) and sucessfully completed the imaging procedure, of whom 25 had coronary angiography. Only 6 of the 68 patients demonstrated reversible septal defects on thallium imaging. Of these 6 patients, 3 underwent coronary angiography and all of them had significant (> 70%) LAD stenosis. Therefore, at most only 4% of the patients with LBBB had a false-positive reversible septal defect. Three additional patients had fixed septal defects. Of these three patients, one underwent cardiac catheterization and was found not to have significant LAD stenosis. The results from this study suggest that adenosine/thallium imaging is associated with an acceptably low frequency of false-positive septal defects and should be used as an alternative to exercise/thallium in patients with LBBB.

This study assesses the causes of colonic localization of labeled white blood cells (WBCs) in critically ill patients who had undergone leukocyte scintigraphy for suspected infection. Forty-two patients showed abdominal or pelvic WBC localization; 20 of these had a pattern of colonic localization, and some also showed a pattern of small bowel activity. Eight of the 20 patients had documented gastrointestinal bleeding. White blood cell scintigraphy in these eight patients showed a pattern of multifocal and/or regional bowel activity that changed in intensity and location from early (3-5-hour) to delayed (18-28-hour) images. In contrast, 5 of the 6 patients with documented pseudomembranous colitis (PMC) showed intense WBC localization involving most of the colon. In 3 of these 5 patients, early and delayed images were acquired and showed a relatively constant pattern of WBC localization. The sixth PMC patient had been treated with vancomycin before leukocyte scintigraphy and showed minimal distal small bowel activity on early images and only mild regional colonic activity on delayed images. As in the patients with gastrointestinal bleeding, the remaining six patients showed either focal or regional activity of variable intensity that changed over time. In critically ill patients, gastrointestinal bleeding and PMC accounted for 14 of the 20 patients in which labeled leukocyte scintigraphy exhibited colonic activity. A pattern of diffuse, intense colonic radiotracer activity which persists from early to delayed imaging strongly suggests the presence of PMC in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Determining the etiology of a focal lesion seen on bone scan in patients with primary tumors usually requires the use of other imaging procedures or biopsy. Single positron emission computed tomography (SPECT) with high resolution multidetector systems can localize the specific site of a vertebral lesion and in this way potentially differentiate between benign and metastatic disease. SPECT images of the lower thoracic and lumbar spine were reviewed for lesion location and intensity by two experienced interpreters. Follow-up data were adequate to ascertain the cause of 71 lesions seen on SPECT in 29 patients. Twenty-six of these lesions were not seen on planar images. Of the 71 lesions, 44 were benign and 27 metastatic. Of the 15 lesions where the pedicle was involved, 11 were found to metastatic. There were a total of 14 facet lesions, 9 of which were present in vertebra with no lesions at sites other than the facets. All 9 of these isolated facet lesions turned out to be benign. Lesion intensity did not distinguish benign from malignant disease. We conclude that SPECT imaging is useful in determining the etiology of focal lesions seen on bone scan in patients with a known primary tumor referred for evaluation of metastatic disease.

Rationale and Objectives: Simultaneous single-photon emission computed tomography (SPECT) neuroimaging with both technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and iodine-123 (123I) N-isopropyl-iodoamphetamine is a recently introduced method with potential for assessing activation phenomena in the brain. However, there is limited information on the accuracy of the technique for detecting focal cortical sites of neuroactivation. We determined, in vitro, what levels of activation could be detected as a function of the size of the activated region., Methods: A Lucite brain phantom was filled with both 123I and 99mTc so as to simulate both a nonactivated state (123I) along with focal sites of activation (99mTc). Simulated activations ranged from 0 to 18% in volumes of 7, 14, 20, and 27 cm3. Imaging was performed with a triple-detector gamma camera using a 10% symmetric window at 140 keV and 10% asymmetric window around 159 keV. No correction was made for gamma cross-talk. To determine whether a simulated activation was "detected," the 99mTc: 123I count ratios in the activated regions were compared by t test with ratios in nonactivated regions of similar volume. Detection sensitivities also were calculated as the fraction of the activated 99mTc: 123I ratios that were greater than the mean + 2 standard deviations of the corresponding nonactivated ratios., Results: All sites of simulated activations of 10% or greater were detected. The detection sensitivity was 100% (95% confidence interval, 90-100%) for the two largest chambers with simulated activations of 13-18%. Activations in the 3-6% range, in the same-sized chambers, were detected with a limited sensitivity (67% with a confidence interval of 45-84%). In the 14-cm3 chamber, simulated activations in the 13-18% range were detected with 90% sensitivity (confidence interval, 74-98%). In general, the detection sensitivity was greater for larger chambers and higher levels of simulated activation., Conclusion: We conclude that the dual-radioisotope technique using triple-detector SPECT systems and low-energy all-purpose (LEAP) collimators should be highly reliable for identifying focal brain activations above 13% that cover at least 14 cm3 of brain cortex. Smaller, less intense sites of activation will be detected with reduced frequency. These conclusions are based on our assessment of only the physical parameters involved in this methodology and other factors (e.g., the possibility that the relation between cerebral radiotracer concentration and regional cerebral blood flow) may affect the results obtained with patients.

Objective: This prospective study was designed to compare the sensitivity and specificity of a relatively simple examination, 201Tl chloride single-photon emission CT (SPECT), with a more complex examination, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), in patients thought to have recurrent brain tumor. Because both agents have been shown to be markers of viable tumor, we hypothesized that their sensitivity and specificity should be the same., Subjects and Methods: Nineteen patients with evidence of recurrent tumor on CT or MR images were studied with both 201Tl SPECT and FDG PET imaging. Two patients were examined twice, so a total of 21 studies were evaluated. The 201Tl SPECT and FDG PET examinations were performed on the same day in 17 patients, and the remaining four examinations were done within 1 week of one another. Three reviewers independently interpreted each Tl SPECT and PET scan. Inappropriate regional increases in 201Tl or FDG activity were considered indicative of tumor recurrence. Sensitivity and specificity values were based on biopsy results and clinical follow-up. The final diagnosis was tumor recurrence in 16 cases and radiation necrosis in 5 cases. The relationship of scan results to survival was analyzed., Results: The sensitivity and specificity of the 201Tl examination for detecting tumor recurrence were 11 (69%) of 16 and two (40%) of five, respectively; values for the FDG PET examination were 13 (81%) of 16 and 2 (40%) of 5, respectively. In patients with recurrent tumors less than 1.6 cm in size, results were false-negative in four 201Tl SPECT examinations and three FDG PET studies. All tumor lesions 1.6 cm or larger (n = 8) were detected. Agreement among the three nuclear medicine specialists was complete for each of the 201Tl SPECT scans. There was disagreement on the interpretation of five (24%) of the 21 FDG PET scans, which was resolved by consensus. Scintigraphic findings did not correlate with patients' survival times., Conclusion: We were unable to detect a statistically significant difference in sensitivity or specificity between the 201Tl SPECT and FDG PET scans. Both techniques were sensitive for tumor recurrence with lesions less than 1.6 cm or larger. However, given the greater availability, simplicity, and ease of interpretation and the lower cost of the 201Tl SPECT studies, this technique should be considered for detection of tumor recurrence with lesions that are demonstrated to be 1.6 cm or larger on CT or MR examinations.

This pilot study was undertaken to generate preliminary data on the accuracy of captopril-enhanced renal scintigraphy with a relatively new radiopharmaceutical, 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) for detecting significant renal artery stenosis. Truth data was based either on arteriographic or outcome criteria (blood pressure response to therapy). Twenty-seven subjects with suspected renovascular hypertension were studied with baseline and captopril-enhanced 99Tcm-MAG3 renal scintigraphy and renal arteriography. Scan interpretations were expressed as a probability of a significant renal artery stenosis. Scan interpretations were compared with renal arteriographic results, renal vein renin levels, blood pressure values after renal artery repair, and blood pressure control after 4-26 months of clinical follow-up. Using > or = 50% luminal obstruction on arteriography as the reference standard for renal artery stenosis and a high probability scan representing a positive test, the test sensitivity and specificity were 33 and 97%, respectively (using high or indeterminate probability to represent a positive scan, the test sensitivity and specificity were 67 and 83%, respectively). The negative predictive value of a low probability scan for renal artery stenosis was 80%. However, including a measure of renovascular hypertension (blood pressure response to renal artery repair) as the reference standard, the accuracy of the scan improves, with the negative predictive value of a low probability scan for renovascular hypertension increasing to 97%. Scintigraphic results were also positively correlated with renal vein renin values in a statistically significant fashion (two-tailed Fisher exact test statistic = 6.43, P = 0.0219). Captopril-enhanced 99Tcm-MAG3 renal scintigraphy is a moderately accurate technique for detecting renal artery stenosis. More importantly, our preliminary findings suggest that the scintigraphic technique using 99Tcm-MAG3 appears to predict the blood pressure response to renal artery repair in subjects with suspected renovascular hypertension, thereby separating subjects with haemodynamically insignificant renal artery stenosis from those with renovascular hypertension.

99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomographic (SPECT) brain imaging performed in conjunction with balloon test occlusion of the carotid artery has been used to assess risk of neurologic sequelae that might follow permanent surgical ligation of the artery. The predictive value of cortical hypoperfusion during temporary carotid occlusion for adverse neurologic events has been debated in previous publications. We believe that the risk of an adverse event is greater when a reduction in cortical perfusion during balloon test occlusion is associated with crossed cerebellar diaschisis (CCD). To test our hypothesis we evaluated the results of 27 99Tcm-HMPAO SPECT brain studies obtained in association with balloon test occlusions of the carotid artery. In each case we correlated clinical outcome with the presence or absence of regional decreases in cerebral perfusion and CCD. All of the 27 patients were free of neurologic symptoms during the balloon test occlusion. Seventeen of the 27 scintigraphic studies were felt to be abnormal, showing cortical perfusion defects all on the side of the occlusion. Among these 17 patients, five demonstrated CCD. Four of these five CCD patients showed evidence for cerebral cortical ischaemia on the side of the temporary carotid occlusion either shortly after the procedure or following carotid artery sacrifice. Of the remaining 12 patients with regionally reduced cerebral perfusion and no CCD, none showed evidence for cortical ischaemia in association with balloon test occlusion, and five of these 12 patients had carotid ligation without subsequent neurologic sequelae.(ABSTRACT TRUNCATED AT 250 WORDS)

This study investigated the relationship between diminished regional cerebral blood flow (rCBF) and the recovery of fluent speech in aphasia. Single-photon emission computed tomographic brain scans using [123I]N-isopropyl-p-iodoamphetamine were obtained from 14 nonfluent aphasic patients within 30 days of cerebral infarction. Measurements of speech fluency were acquired initially and at 3 months after infarction. Nearly all of the patients exhibited significant hypoperfusion to combinations of the anterior and posterior regions of the basal ganglion, the periventricular white matter, and the inferior frontal regions. Only the inferior frontal area was significantly associated with recovery of fluent speech. This region was hypoperfused in 4 of 5 patients with poor recovery while 8 of the 9 patients with good speech fluency recovery demonstrated normal rCBF to the inferior frontal region.

We prospectively compared auscultatory findings of third heart sounds with radionuclide ventriculographic analysis of systolic and diastolic function. Cardiac auscultation was done to detect an S3 in patients referred for radionuclide ventriculographic analysis of ventricular function. Of 49 adult men with the diagnosis of chronic, nonvalvular heart failure who were referred for the evaluation of heart failure, 22 (45%) at the time of the ventriculography had an S3 present on examination. For the entire study group, the radionuclide ventriculography-derived ejection fraction was 33% +/- 19.5 (mean +/- SD) with a range of 6% to 74%. The peak ejection rate was 2.05 +/- 1.09 end-diastolic volume per second with a range of 0.30 to 4.56. The peak filling rate was 1.97 +/- 1.07 end-diastolic volume per second with a range of 0.44 to 3.94, and the time to peak filling rate was 0.18 +/- 0.11 per second with a range of 0.05 to 0.61. The presence of an S3 was associated with a reduced ejection fraction and also with impaired diastolic function as determined by the peak filling rate. The sensitivity and specificity for the S3 in detecting abnormal systolic function (ejection fraction < 50%) were 51% and 90%, respectively, with a positive predictive value of 95% and a negative predictive value of only 32%. For an ejection fraction of less than 30%, the S3 had a sensitivity and specificity of 78% and 88%. The presence of an S3 was highly predictive of an abnormal ejection fraction. The absence of an S3, however, is not uncommon in patients with a mildly impaired ejection fraction.

Although surgical treatment of nontoxic multinodular goiter remains the most effective therapy, I-131 is a reasonable alternative in cases where thyroidectomy is not appropriate. Selection of I-131 activity in the management of nontoxic multinodular goiter has largely been empirical. The use of dosimetric measurements in guiding I-131 therapy in the treatment of a patient with a recurrent, nontoxic, multinodular goiter is described.

Recent progress in the treatment of coronary artery disease is reviewed from the standpoint of changes in lifestyle, surgical techniques to revascularize the myocardium and a variety of medical interventions. Among the medical modalities, heparin appears to have a greater potential than any other agent tested to neutralize the atherogenic process at most of its stages. This potential is supported by success in clinical trials of heparin administered by intravenous, subcutaneous, pulmonary, sublingual and topical routes. The suggested self-administration of low-dose heparin by inhalation appears to be well justified and easily adaptable to home therapy. The summarized evidence suggests the need for further clinical trials to test the use of heparin in the prophylaxis of atherosclerotic disease.

Background and Purpose: The purpose of this study was to determine utility of late N-isopropyl-p-(iodine-123)-iodoamphetamine distribution in predicting neurological and language outcome., Methods: We prospectively studied 29 patients with unilateral hemispheric ischemic cerebral infarction using the neuroimaging method of single-photon emission computed tomography and the above tracer. Four different imaging measures reflecting late tracer distribution or redistribution and three measures indicative of the patients' overall neurological or language outcome at 3 months were used in the data analysis. All patients had neuroimaging within 30 days of infarction, and 14 patients were imaged within 10 days of infarction. Data analysis was performed for all patients combined and then separately on the groups imaged within 10 days of and more than 10 days after infarction., Results: The volume of the late image defect significantly correlated with one measure of neurological outcome in the whole group and in those imaged more than 10 days after cerebral infarction. However, these results are difficult to explain based on the present understanding of the physiology of late N-isopropyl-p-(iodine-123)-iodoamphetamine distribution., Conclusions: We feel that the pattern of late N-isopropyl-p-(iodine-123)-iodoamphetamine distribution is probably not useful as an independent predictor of neurological and language outcome.

The pathogenesis of gastroesophageal reflux (GER) is not fully understood. There have been reports that delayed gastric emptying is a contributing factor in some patients. To determine whether delayed gastric emptying plays a role in the genesis of GER, we correlated gastric-emptying measures obtained by scintigraphic techniques with the degree of acid reflux assessed by esophageal pH monitoring. Ten patients, all of whom had evidence of esophageal mucosal disease and severe acid reflux, were studied. Four of the 10 patients with reflux had prolongation in the lag phase of gastric solid emptying, and one of the four showed prolonged gastric-emptying t1/2. There was no significant difference, however, in the mean gastric-emptying t1/2 between a control group and the patient group. Furthermore, there was no correlation between gastric-emptying measures and degree of acid reflux. We conclude that in this group of 10 patients with severe GER, delayed gastric emptying does not play an important role in the development of gastroesophageal reflux.

Anatomic features of carotid artery stenosis, as defined angiographically, do not necessarily correlate with the hemodynamic significance of the narrowing. The concept of regional cerebral vasodilatory (or perfusion) reserve has been advocated as a means of defining the hemodynamic compromise associated with carotid lesions. We evaluated the feasibility of using SPECT imaging with 5% CO2 using I-123 IMP (N-isopropyl iodoamphetamine) or Tc-99m HMPAO (hexamethylpropylene amineoxime) to measure cerebral perfusion reserve. Imaging was performed on six asymptomatic subjects and one patient with a history of transient ischemic attacks but no evidence of carotid artery disease. A perfusion reserve index (PRI) was defined to represent the percent increase in blood flow during 5% CO2 breathing in regions supplied by the middle cerebral artery normalized for injected dose and changes in blood pressure. Significant increases in cerebral perfusion were seen in six of the seven subjects studied while breathing the 5% CO2 (P less than 0.01). The mean of the PRI values for the seven subjects was 32%, with a range of -5% to 58%. We conclude that SPECT imaging with IMP or HMPAO can be used to quantitatively measure the cerebral perfusion response to 5% CO2.

Reports on clinical trials with subcutaneous and intrapulmonary administration of low-dose heparin suggest that it may be an attractive therapeutic modality for the treatment of coronary artery disease because of unprecedented reduction in mortality of treated subjects. As a preliminary to a clinical trial with low-dose intrapulmonary heparin, a pilot study was conducted on three subjects. It compares overall circadian responses of 37 blood variables following intrapulmonary administration of heparin (10,500-18,800 U) in the morning (0800 h) and in the evening (2000 h). After each of these times, blood samples, mostly at 3 h intervals for the ensuing 27 h, were analyzed for heparin, APTT, TT, functional fibrinogen, CBC, enzymes, lipids, electrolytes, and hormones. Each time series was analyzed for circadian rhythm by the least-squares fit of a 24 h cosine and circadian mesors were compared by the Bingham test of rhythm parameters. Following heparin in the evening, but not in the morning, a statistically significant increase in circulating heparin levels, as well as directional increases in APTT and TT and decreases in fibrinogen, were observed in all three subjects. Same direction changes in several other variables were also observed. It is concluded that inhalation of heparin in low-dose levels results in variable circadian effects on blood parameters measured, ranging from no changes in their levels to minimal within normal range changes, and that these effects are dependent upon the timing of dose administration. It is suggested that the timed self-administration of low-dose heparin by inhalation be seriously considered for long-term clinical trials in the treatment and prevention of atherosclerosis.

Xenon-133 washout phase imaging is often used to help determine whether the etiology of a perfusion defect is embolic or due to pulmonary parenchymal pathology, such as chronic obstructive pulmonary disease. This study was designed to evaluate the pulmonary blood flow patterns associated with isolated defects on xenon washout images. Scintigraphic lung studies were reviewed until 100 cases with abnormal ventilation results were obtained. Ventilation abnormalities were compared with the corresponding perfusion scan results at the same anatomic site. Of the 208 individual lung regions with xenon abnormalities, 111 showed isolated washout defects (that is, with normal washin). Ninety-four of these 111 sites showed either normal perfusion or a small, nonsegmental corresponding perfusion defect. Three segmental perfusion defects were noted in association with isolated xenon retention. In each of these cases, however, the patient was felt actually to have pulmonary embolism. Thus, it is recommended that, for interpretation of scintigraphic images in the assessment of pulmonary embolism, lung pathology associated with isolated xenon retention not be considered a potential cause for large or segmental perfusion defects.

Urine samples were collected at 3-hr intervals over a single 24-hr period from each of seven clinically healthy men who ranged in age from 21-25 years. Urines at each collection time were subsequently pooled using 20% of each volume and serially dialyzed against ammonium-barbituric acid buffer (pH 7.35 +/- 0.02), using a cellulose membrane permeable to compounds of less than 12,000-14,000 molecular weight (mw). When the dialyzed portions were then analyzed for total proteins, the sum of proteins in eight pools amounted to 74 mg. A 1 ml aliquot of each pool, representing approximately 50 micrograms of proteins, was concentrated and reconstituted. Approximately 20 micrograms of reconstituted proteins were then subjected to polyacrylamide gel electrophoresis. The stained gel was then scanned by laser densitometry and planimetry. Each aliquot revealed eight segments as identified by Coomassie and silver staining. Their molecular weights, estimated by extrapolation from concurrently run protein standards, and their total protein amounts were: 116,000 mw (9.44 mg), 91,000 mw (3.3 mg), 68,000 mw (11.58 mg), 53,000 mw (2.58 mg), 43,000 mw (9.12 mg), 32,000 mw (7.13 mg), 24,000 mw (4.52 mg) and 20,000 mw (5.27 mg). A statistically significant rhythm (P = 0.022 from ANOVA and 0.011 from Single Cosinor) was found for the excretion of total proteins, with an acrophase in the afternoon (1537) for these diurnally-active subjects.

Radionuclide scintigraphy is a safe and accurate means of detecting postoperative urologic complications in renal transplant recipients. Early identification of urinary leakage coupled with aggressive intervention significantly reduces the associated morbidity and mortality. Perivesical extravasate may be difficult to distinguish from adjacent or nearby bladder activity on scintiscan. Clarification of actual bladder contour and determination of its exact location within the pelvis may resolve such uncertainties. We describe imaging techniques that define the anatomic extent of the bladder and demonstrate our scintigraphic assessment of perivesical extravasation.