Technology-based interventions and trainings to reduce the escalation and impact of alcohol problems.

There has been a rapid increase in the development of technological innovations to reduce the escalation and impact of alcohol problems among adolescents and adults. Technology-based interventions offer the possibility of reaching individuals who otherwise might not seek treatment, (e.g., those in remote areas, those not perceiving a need for treatment, or others who may resist treatment). This article describes four case examples of technology-based interventions for risky drinking: 1) a freely available and interactive website that provides individualized feedback and information on risky drinking patterns; 2) a brief intervention for adolescents that provides individualized feedback to teens regarding their alcohol use; 3) a computer-delivered screening and brief intervention for alcohol use among pregnant women, and 4) a simulation program for training social workers in screening and brief intervention. These case examples highlight how technology may have a role in addressing the Alcohol Misuse Grand Challenge.

Somatostatin receptor subtype specificity and in vivo binding of a novel tumor tracer, 99mTc-P829.

Recent data suggest that somatostatin receptors (SSTRs) are expressed on various tumor cells. High-level expression of SSTR on the tumor cell surface provides the basis for the successful clinical use of radiolabeled ligands for the in vivo localization of tumor sites. We have characterized the in vitro binding properties of the novel SSTR ligand 99mTc-P829 using primary human tumors (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small cell and non-small cell lung cancer, and melanomas; n = 28), various tumor cell lines, and COS7 cells transfected with the human SSTR (hSSTR) subtypes 1, 2, 3, 4, and 5. 99mTc-P829 bound to primary tumor cells and tumor cell lines with high affinity and high capacity. The dissociation constants (Kd) ranged between 1 and 20 nM. 99mTc-P829 also bound with high affinity to the transfected hSSTR2 (Kd, 2.5 nM), hSSTR5 (Kd, 2 nM), and hSSTR3 (Kd, 1.5 nM). Binding of 99mTc-P829 to hSSTR3 was found to be displaceable by unlabeled P829/([ReO]-P829), SST-14, and vasoactive intestinal peptide (VIP; IC50, 2 nM) and, less effectively, by Tyr3-octreotide (IC50, 20 nM). In contrast, the binding of 99mTc-P829 to hSSTR2 and hSSTR5 could be displaced by P829/([ReO]-P829) and Tyr3-octreotide but not by VIP. 99mTc-P829 scintigraphy revealed in vivo binding to primary or metastatic tumor sites in seven of eight patients with breast cancer and six of six patients with melanoma. In summary, our data show that 99mTc-P829 binds with high affinity to many different types of primary and cloned tumor cells. Furthermore, our data identify hSSTR2, the VIP acceptor hSSTR3, and hSSTR5 as the respective target receptors. Because these receptors are frequently expressed at high levels on primary tumor cells, 99mTc-P829 appears to be a promising novel peptide tracer for tumor imaging.

Somatostatin receptor-binding peptides labeled with technetium-99m: chemistry and initial biological studies.

The synthesis of peptides which possess a high affinity for the somatostatin receptor and contain a chelator for the radionuclide technetium-99m is described. The target compounds were designed such that they would form stable, oxotechnetium(V) chelate complexes in which the Oxorhenium(V) chelate complexes of these peptides were prepared as nonradioactive surrogates for the technetium complexes. Peptide oxorhenium complexes and Tc-99m complexes eluted closely upon HPLC analysis. The receptor-binding affinities of both the free and rhenium-coordinated species were measured in vitro. The binding affinities of the free peptides (Ki's in the 0.25 - 10 nM range) compared favorably with [DTPA]octreotide (Ki = 1.6 nM), which, as the indium-111 complex, is already approved for somatostatin receptor (SSTR)-expressing tumor imaging in the United States and Europe. Furthermore, the rhenium-coordinated peptides had binding affinities which, in many cases, were higher than those of the corresponding free peptides, with several complexes having a Ki's of 0.1 nM. Some of the more potent SSTR-binding peptides were labeled with technetium-99m and assessed in an in vivo study with tumor-bearing rats. The 99m Tc-labeled peptides prepared in this study should be useful as SSTR-expressing tumor-imaging agents due to their high SSTR-binding affinities, ease of preparation, and, because they are low molecular weight peptides, expected pharmacokinetics characterized by rapid tracer excretion from the body resulting in high-contrast images.

Acute thromboscintigraphy with (99m)Tc-apcitide: results of the phase 3 multicenter clinical trial comparing 99mTc-apcitide scintigraphy with contrast venography for imaging acute DVT. Multicenter Trial Investigators.

UNLABELLED: (99m)Tc-apcitide (formerly known as (99m)Tc-P280) is a radiolabeled peptide that binds with high affinity and specificity to the glycoprotein IIb/IIIa receptors expressed on the activated platelets that are involved in acute thrombosis. The purpose of the phase 3 multicenter clinical trials was to compare (99m)Tc-apcitide scintigraphy with contrast venography for imaging acute deep venous thrombosis (DVT). METHODS: A total of 280 patients were enrolled in 2 clinical trials conducted in North America and Europe. Patients were to be within 10 d of onset of signs and symptoms of acute DVT or within 10 d of surgery associated with a high risk of DVT. (99m)Tc-apcitide scintigraphy and contrast venography were to be performed within 36 h. Planar scintigraphic images were obtained at 10, 60, and 120-180 min after injection. (99m)Tc-apcitide scintigrams and contrast venograms were read with masking and also by the institutional investigators. RESULTS: Of a total of 243 patients who were evaluable, 61.7% were receiving heparin at the time of imaging. Masked reading of (99m)Tc-apcitide scintigraphy, compared with masked reading of contrast venography, had a sensitivity, specificity, and agreement of 73.4%, 67.5%, and 69.1%, respectively, which met the prospectively defined target efficacy endpoint in both trials. Institutional reading of (99m)Tc-apcitide scintigraphy, compared with institutional reading of contrast venography, had a sensitivity, specificity, and agreement of 75.5%, 72.8%, and 74.0%, respectively. However, the entire trial population included patients with a history of DVT who may have had old, nonacute venous thrombi that could confound the venography results. Therefore, data from patients having no history of DVT or pulmonary embolism and who presented within 3 d of onset of signs and symptoms (n = 63), i.e., patients for whom a venogram would be expected to be positive only if acute DVT were present, also were analyzed as a subset. In these patients, institutional reading of (99m)Tc-apcitide scintigraphy, compared with institutional reading of contrast venography, had a sensitivity, specificity, and agreement of 90.6%, 83.9%, and 87.3%, respectively. CONCLUSION: (99m)Tc-apcitide scintigraphy is a new diagnostic modality that is highly sensitive for imaging acute DVT.

A comparison of two cerebral perfusion tracers, N-isopropyl I-123 p-iodoamphetamine and I-123 HIPDM, in the human.

Both N-isopropyl I-123 p-iodoamphetamine (IMP) and I-123 HIPDM have been advocated as radiotracers for assessing regional cerebral perfusion. We compared the biodistribution of the two tracers in 19 patients without evidence of neurological disease. Following intravenous injection, both tracers accumulated initially in the lung. Early after injection the fraction of the total brain uptake was higher for I-123 HIPDM than for I-123 IMP. The peak brain activity for I-123 IMP was higher than for I-123 HIPDM . Brain activity was unchanged with both tracers between 30 and 60 min after injection. Tomographic images were similar in appearance for both tracers. No eye uptake greater than background was observed with either tracer in any patient at 2, 24, and 48 hr. I-123 IMP is superior for tomographic imaging because of its higher brain uptake, whereas I-123 HIPDM may be superior for studies performed during rapid changes in blood flow.

Detecting deep venous thrombosis with technetium-99m-labeled synthetic peptide P280.

UNLABELLED: Scintigraphy, using small, thrombus-avid, synthetic peptides labeled with gamma-emitting nuclides is an innovative approach to the noninvasive detection of acute deep venous thrombosis (DVT). The goal of this study was to evaluate clinically 99mTc-P280 for imaging DVT. The peptide P280 is a 26 amino acid dimer that binds with high affinity to the GPIIb/IIIa receptor expressed on activated platelets and can be labeled with 99mTc. METHODS: Scintigraphy with 99mTc-P280 (10-22 mCi) was performed in nine patients with clinical suspicion and diagnostic evidence of DVT. Planar and tomographic images of the legs, abdomen/pelvis, chest and head were obtained immediately, 1, 2, 4 and 24 hr after injection. RESULTS: No adverse effects were noted after 99mTc-P280 administration in any patient. Positive visualization of thrombi occurred in eight of nine cases with confirmed DVT within 1 hr of tracer injection. The majority of the patients had recent onset of DVT symptoms (less than 3 wk), while the only negative case was diagnosed 42 days earlier and was likely related to an accident 7 mo earlier. Thrombi-to-background ratios were essentially constant over the study. Technetium-99m-P280 accumulation was also discernible in two patients with pulmonary embolism, while in a third patient the radiotracer concentrated in a cerebellar hemangioblastoma. CONCLUSION: These human studies indicate that 99mTc-P280 is a potentially safe and sensitive procedure for diagnosing DVT and pulmonary embolism. It also may have substantial utility in monitoring active venous thrombosis.

Effect of reperfusion and hyperemia on the myocardial distribution of technetium-99m t-butylisonitrile.

Technetium-99m t-butylisonitrile ([99mTc]TBI) is a promising new radiotracer for myocardial imaging. Its myocardial uptake is sufficiently high in humans to permit planar, tomographic, and gated images of excellent technical quality. We studied the behavior of [99mTc]TBI in the dog at rest and under conditions of hyperemia and reperfusion in order to determine the relationship between [99mTc]TBI myocardial concentration and blood flow. After permanent occlusion of the left anterior descending artery, the correlation between the relative myocardial concentration of [99mTc]TBI and regional myocardial blood flow (RMBF) measured with radiolabeled microspheres was excellent. In a dog model of transient hyperemia, the concentration of [99mTc]TBI was directly related to blood flow but underestimated the degree of hyperemia. Technetium-99m TBI redistributed into transiently ischemic myocardium. The myocardial concentrations of [99mTc]TBI and thallium-201(201TI) in transiently ischemic myocardium were similar at 10 and 30 min following reperfusion and were significantly higher than blood flow prior to reperfusion. When [99mTc]TBI was injected into the left anterior descending artery, the washout was slow, falling to 78% of initial activity at 120 min after injection. In conclusion, [99mTc]TBI reflects regional myocardial blood flow accurately in ischemic and normal resting myocardium and underestimates blood flow at high flows. The rate of myocardial redistribution after reperfusion is similar for [99mTc]TBI and 201TI.

Preclinical evaluation of technetium-99m-labeled somatostatin receptor-binding peptides.

UNLABELLED: We report here the results of studies on the in vitro receptor binding affinity, in vivo tumor uptake and biodistribution of two 99m-Tc-labeled peptides. METHODS: Peptides P587 and P829 were synthesized by N-alpha-Fmoc peptide chemistry, purified by reversed-phase HPLC and characterized by fast-atom bombardment mass spectrometry. The peptides were labeled with 99mTc by ligand exchange from 99mTc-glucoheptonate. In vitro somatostatin receptors (SSTR)-binding affinities of P587, P829 and their oxorhenium complexes, [DTPA]octreotide and In-[DTPA]octreotide were determined in an inhibition assay using AR42J rat pancreatic tumor cell membranes and 125I-[Tyr3]somatostatin-14 as the probe. In vivo single- and dual-tracer studies of 99mTc peptides and 111In-[DTPA]octreotide were carried out using Lewis rats bearing CA20948 rat pancreatic tumor implants. RESULTS: Technetium-99m-P587 and 99mTc-P829 of high-specific activity (>60 Ci (2.2 TBq)/mmole) were prepared in >90% radiochemical yield. P587 and P829 had a Ki = 2.5 nM and 10 nM, respectively. [ReO]P587 and [ReO]P829, representing the 99mTc complexes, had Ki = 0.15 nM and 0.32 nM, respectively. In comparison, [DTPA]octreotide and In-[DTPA]octreotide had Ki = 1.6 and 1.2 nM, respectively. In vivo tumor uptake of 99mTc-P587 and 99mTc-P829 was high (4.1 and 4.9%ID/g at 90 min postinjection compared to 2.9% for 111In-[DTPA]octreotide). Tumor/blood and tumor/muscle ratios at 90 min postinjection were 6 and 33 for 99mTc-P587, 21 and 68 for 99mTcP829, and 22 and 64 for 111In-[DTPA]octreotide. CONCLUSION: The high SSTR-binding affinity and high receptor-specific and saturable in vivo tumor uptake indicate that 99mTc-P587 and 99mTc-P829 are promising radiotracers for the clinical detection of SSTR-expressing tumors and other tissues by 99mTc gamma scintigraphy.

Thrombus imaging with a technetium-99m-labeled activated platelet receptor-binding peptide.

UNLABELLED: The objective of this work was the preclinical evaluation of 99mTc-P280, a 99mTc-labeled peptide having high affinity and specificity for the GPIIb/IIIa receptor expressed on activated platelets, for use as a thrombus imaging agent. METHODS: The affinity and specificity of P280 peptide for the GPIIb/IIIa receptor was assessed by the inhibition of ADP-stimulated human platelet aggregation, the inhibition of the binding of fibrinogen to the GPIIb/IIIa receptor and the inhibition of the binding of vitronectin to the vitronectin receptor. P280 peptide was radiolabeled with 99mTc by ligand exchange using 99mTc-glucoheptonate. The ability of 99mTc-P280to detect thrombi in vivo was assessed using a canine venous thrombosis model and the biodistribution of 99mTc-P280 was determined in rats and rabbits. RESULTS: P280 peptide had an IC50 of 79 nM for the inhibition of aggregation of human platelets in platelet rich plasma, an IC50 of 6.8 nM for the inhibition of fibrinogen binding to the GPIIb/IIIa receptor and an IC50 of 13 microM for the inhibition of vitronectin binding to the vitronectin receptor, showing the high in vitro receptor binding affinity and specificity of the peptide. 99mTc-P280 was readily prepared in > or = 90% radiochemical and yield purity and provided images of femoral vein thrombin in the canine model by 1 hr postinjection (thrombus-to-blood ratio of 4.4 and thrombus-to-muscle ratio of 11 at 4 hr). Dog, rat and rabbit studies all showed rapid clearance of the radiotracer from the blood and rapid renal excretion. CONCLUSION: The combination of high in vitro receptor-binding affinity and specificity, in vivo thrombus imaging and fast clearance support the evaluation of 99mTc-280 as a clinical imaging agent.

Technetium-99m-white blood cell-specific imaging agent developed from platelet factor 4 to detect infection.

UNLABELLED: We have developed a leukocyte-avid, 99mTc-labeled peptide (P483H) as a potential imaging agent for infection. P483H contains the heparin-binding region of platelet factor-4 (PF-4) and a lysine-rich sequence for rapid renal clearance. Technetium-99m-P483H was evaluated for its ability to selectively label white blood cells (WBCs) in vitro and to detect focal E. coli infections in rabbits. METHODS: Technetium-99m-P483H was incubated with citrated whole human blood, layered onto WBC isolation media and subjected to density gradient centrifugation to measure WBC-associated radioactivity. Indium-111-WBCs and 99mTc-gluceptate were used as controls. In the in vivo model, E. coli infected rabbits were imaged and necropsied 4 hr after administration of 99mTc-P483H. Infected and contralateral control muscles were evaluated for %ID, %ID/g, Imax (muscle sample showing the highest uptake, i.e., %ID/g) and Imax-to-blood and Imax-to-control muscle ratios. Indium-111-WBCs, 111In-DTPA, 131I-albumin (HSA), 99mTc-nanocolloid, 67Ga and 99mTc-gluceptate were evaluated as in vivo controls. RESULTS: Technetium-99m-P483H associated predominantly with WBCs in vitro, and 99m-Tc-P483H provided high contrast images of infection in vivo. In vitro, 73% of 99mTc-P483H radioactivity was associated with WBCs. Technetium-99m-P483H outperformed 111In-WBCs, 111In-DTPA, 131I-albumin, 99mTc-nanocolloid, 67Ga-citrate and 99mTc-gluceptate with an infection Imax average of 0.062 %ID/g (+/- 0.029; n = 48). Technetium-99m-P483H also outperformed all controls, including 111In-WBCs, 111In-DTPA, 131I-albumin, 99mTc-nanocolloid, 67Ga-citrate and 99mTc-gluceptate. The Imax-to-blood and Imax-to-control muscle ratios for 99mTc-P483H averaged 3.1 (+/- 2.4) and 26.8 (+/- 16.8), respectively, and again outperformed all controls. CONCLUSION: Technetium-99m-P483H associates predominantly with WBCs in vitro and identified focal infections in vivo within 4 hr versus conventional imaging agents. Additionally, the agent showed rapid blood clearance and exclusive renal excretion, which provides a clear abdominal field for imaging abdominal infections.

Hexakis(carbomethoxyisopropylisonitrile) technetium(I), a new myocardial perfusion imaging agent: binding characteristics in cultured chick heart cells.

Cellular kinetics and binding characteristics of hexakis(carbomethoxyisopropylisonitrile) technetium(I) (Tc-CPI), a new cationic, highly lipophilic myocardial perfusion imaging agent, were evaluated in chick embryo heart cells grown in monolayer culture. Myocytes showed uptake of Tc-CPI to a plateau level with a half-time (t1/2) of 4.1 +/- 0.7 min (mean +/- s.e.m.; n = 6); t1/2 appeared independent of extracellular Tc-CPI concentration. Plateau level Tc-CPI uptakes (10(-16) to 10(-11) mole Tc-CPI/mg cell protein) were a linear function of extracellular Tc-CPI concentration (range: 10(-13)M to 10(-8)M, respectively). Tracer 99mTc-CPI uptake (binding) was not competitively displaced by carrier 99Tc-CPI. Uptake was temperature-sensitive; however, several inhibitors of cationic membrane transport (ouabain, amiloride, bumetanide, and verapamil) showed no significant effect. Extreme alkalinization of external load solution (pHo approximately 8.5) partially inhibited Tc-CPI uptake; however, intracellular pH changes showed no effect. Washout from contractile preparations could be described by a two component system: a fast component (myocytes) with a t1/2 approximately 4.5 min and a slow component (fibroblasts) with a t1/2 approximately 40 min. Cell fractionation experiments showed most of the activity to be associated with the cell membrane fraction. The data do not demonstrate a specific mechanism for uptake of Tc-CPI; however, results suggest binding to myocytes in a manner proportional to the delivery of the complex to the extracellular spaces. Such properties would be desirable for a myocardial perfusion imaging agent.

I-123 HIPDM brain imaging with a rotating gamma camera and slant-hole collimator.

The performance of a slant-hole collimator was compared with that of a standard straight-bore, low-energy collimator for tomographic imaging of I-123-iodinated amine brain agents. Improved in-slice resolution was due to the greater proximity between collimator and the subjects' heads. We conclude that high quality tomographic images of the brain can be obtained from rotating cameras equipped with slant-hole collimators.

A new Tc-99m-labeled myocardial imaging agent, hexakis(t-butylisonitrile)-technetium(I) [Tc-99m TBI]: initial experience in the human.

The cationic complex Tc-99m hexakis(t-butylisonitrile)technetium(I) (TBI) has been shown to concentrate in the myocardial tissue of several animal species. In the present preliminary study, the biodistribution of this material was examined in four normal subjects and in two patients with coronary artery disease. In three normal humans injected at rest, planar, tomographic, and gated myocardial images of high technical quality were obtained between 1 and 4 hr after injection. In one subject studied both at rest and during maximal exercise, the lung and heart activities were similar, whereas the liver-to-heart activity ratio was 3:1 at 60 min at rest compared with 1.8:1 with maximal exercise. In two patients with coronary artery disease, transient ischemia appeared as a perfusion defect up to 4 hr after injection at maximal exercise, and the image appeared normal when Tc-99m TBI was administered at rest. The images of areas of infarction appeared abnormal after injection at rest and after injection during exercise. Technetium-99m TBI is a promising myocardial imaging agent that may permit high-quality planar, gated, and tomographic imaging of myocardial ischemia and infarction.

Pre-clinical evaluation of technetium-99m platelet receptor-binding peptide.

UNLABELLED: P748 is a dimeric peptide which incorporates two high affinity GPIIb/IIIa receptor-binding domains and a novel 99mTc binding sequence, which provides the platelet imaging agent 99mTc-P748. The aim of this study was to evaluate 99mTc-P748 preclinically for use as a hot spot scintigraphic thrombus imaging agent. METHODS: Technetium-99m-P748 was prepared by either a ligand exchange or a one-vial kit. The oxorhenium congener, [ReO]P748, was prepared by ligand exchange from Bu4NReOBr4. The binding of P748 peptide and [ReO]P748 to GPIIb/IIIa receptors on activated platelets was assessed by their inhibition of ADP stimulated human platelet aggregation in platelet rich plasma (PRP). The localization of 99mTc-P748 in deep vein and pulmonary thrombi was assessed in a canine thrombosis model and the biodistribution of 99mTc-P748 was determined in rats. RESULTS: P748 peptide inhibited the aggregation of human platelets in PRP by 50% at a concentration (IC50) of 28 nM and [ReO]P748 had an IC50 of 36 nM showing the high in vitro receptor binding affinity of both the peptide and its rhenium complex (and by analogy its technetium complex). Technetium-99m-P748 was readily prepared at room temperature in 15 min in > or = 90% radiochemical yield and purity and provided definitive images of femoral vein thrombi within 20 min and pulmonary thrombi, within 1 hr in the canine model. Femoral vein thrombus-to-blood and thrombus-to-muscle ratios at 4 hr averaged 6.7 and 46, respectively. Pulmonary thrombus-to-blood and thrombus-to-normal lung ratios at 4 hr averaged 29 and 27, respectively. Dog and rat studies both showed rapid clearance of the radiotracer from the blood and with no significant hepatobiliary excretion but with notable early kidney retention. CONCLUSION: The combination of high in vitro receptor-binding affinity, high thrombus uptake and definitive in vivo images of both femoral vein and pulmonary thrombi show that 99mTc-P748 has considerable potential as a clinical imaging agent for the detection of venous thromboembolism.

Myocardial imaging with technetium-99m CPI: initial experience in the human.

The hexakis(isonitrile)technetium(I) analog [99mTc]carbomethoxyisopropyl isonitrile (CPI) has high myocardial uptake and rapid lung and liver clearance in most animal species. To evaluate [99mTc]CPI as a myocardial imaging agent in the human, we evaluated this tracer in three normals and in six patients with coronary artery disease (CAD). In normals, [99mTc]CPI cleared quickly from the lungs and accumulated in the liver and heart. The liver activity peaked at 10-15 min and cleared through the hepatobiliary system. Planar images were of excellent technical quality with high myocardial to background ratios as early as 10 min after injection. Myocardial activity fell gradually to 76.1 +/- 2.9 (s.d.)% of initial activity by 60 min after injection. In six patients with CAD, myocardial defects were present on planar images up to 2 hr after exercise and injection. In one out of six patients, the defect was not seen 3 hr after injection. In five of the six patients, normal perfusion patterns were observed 1 hr after reinjection of CPI at rest (4 hr after the initial injection). In one patient who developed spontaneous angina prior to reinjection, the perfusion defects persisted. The repeat study 3 days later with injection of [99mTc]CPI at rest was normal. Technetium-99m CPI appears to have excellent physical and biologic properties for use in association with myocardial imaging with exercise.

A multicenter trial with a somatostatin analog (99m)Tc depreotide in the evaluation of solitary pulmonary nodules.

OBJECTIVE: The affinity of various malignant neoplasms including small cell and non-small cell lung cancer for peptide analogs of somatostatin has been well documented. Depreotide is such an analog and can be complexed with technetium-99m ((99m)Tc depreotide) for optimal imaging properties. Using this radiopharmaceutical, solitary pulmonary nodules (SPN) were previously evaluated in a successful phase II/III trial. The results of the larger multicenter phase III study using (99m)Tc depreotide to differentiate malignant and benign etiologies in SPN are now presented. METHODS: Patients with SPN 30 years, and no demonstrable radiographic stability for the prior 2 years were studied. All underwent single-photon emission CT (SPECT) with (99m)Tc depreotide and subsequent tissue histologic examination. Three nuclear medicine specialists blinded to histologic findings examined the SPECT images and scored them as positive or negative based on the presence or absence of activity in the radiographic region of the SPN. The final result was determined by the majority score, which was then compared with the histologic result. RESULTS: Of the 114 individuals studied, 88 had a histologic result compatible with malignant neoplasm. (99m)Tc depreotide scintigraphy correctly identified 85 of this group, with three false-negative determinations compared with histology. There were seven false-positive determinations, including six granulomas and one hamartoma. (99m)Tc depreotide scintigraphy correctly excluded malignancy in 19 of 26 patients with benign histologic findings. The sensitivity of this method was 96.6% with a specificity of 73.1%. CONCLUSION: (99m)Tc depreotide scintigraphy is a safe and useful method for the noninvasive evaluation of SPN with a sensitivity and accuracy comparable to that reported for fluorine-18 fluorodeoxyglucose positron emission tomography.

External imaging of atherosclerosis in rabbits using an 123I-labeled synthetic peptide fragment.

The oligopeptide fragment of apolipoprotein B, SP-4, has demonstrated pronounced uptake in the healing edges of balloon-injured rabbit aortic endothelium. To assess 123I-labeled SP-4 for identification of atherosclerotic plaques by gamma camera imaging, 14 Watanabe heritable hyperlipidemic (WHHL) and 5 normal rabbits were imaged 5 minutes and 12 and 24 hours after intravenous injection of 123I-SP-4. In addition, two WHHL and two normal rabbits were injected with 125I-SP-4 for autoradiography. Twelve of the 14 WHHL, but none of the normal, rabbits had visually apparent focal radioiodine accumulation in the region of the aorta. Focus-to-lung and focus-to-heart count ratios were 2.4 +/- 1.3 and 1.0 +/- 0.4, respectively. Five of the visually positive WHHL rabbits were reimaged 4 and 8 weeks later with 123I-NaI and 123I-SP-2 (an apo E peptide), respectively, as negative controls. Perceptible, but faint, aortic localization of 123I-NaI and of 123I-SP-2 was seen in only one animal each. The distributions of atherosclerotic lesions on photographs of the opened WHHL aortas and of film blackening on 125I-SP-4 autoradiograms were identical. In contrast, the two normal rabbit aortas did not exhibit plaques on photographs or film blackening on autoradiograms. Thus, in an animal model closely simulating human atherosclerotic disease, SP-4 localizes specifically in aortic atherosclerotic lesions.

Localizing infection with a technetium-99m-labeled peptide: initial results.

In vitro-labeled leukocyte imaging is useful for the detection of infection, but an in vivo labeling method is preferable. This study sought to evaluate the safety and efficacy of a leukocyte-avid peptide for the detection of infection, to determine the effects of peptide dose on performance and to compare the peptide with in vitro-labeled leukocytes. A 23-amino acid peptide, P483, containing the platelet factor-4 heparin-binding sequence, was labeled with 99mTc and complexed with heparin (P483H). Thirty patients were injected with 29 microg (n = 11), 145 microg (n = 10) or 290 microg (n = 9) of labeled peptide, and imaged 15 min and 90-120 min later. Early and late images were interpreted individually and jointly. Twenty patients underwent (111)In-labeled leukocyte scintigraphy. Fourteen patients had infection: osteomyelitis (n = 7), vascular graft (n = 2), abscess (n = 2), joint replacement (n = 1), surgical wound (n = 1) and pneumonia (n = 1). There were 10 adverse events in six patients; all were mild and resolved spontaneously, and without any intervention. The sensitivity, specificity and accuracy were the same for both early and late imaging: 0.86, 0.81 and 0.83, respectively. Interpreting early and late images together did not improve the results. No relationship between peptide dose and study accuracy was found. In patients undergoing both examinations, the accuracies of the peptide and in vitro-labeled leukocyte imaging were identical: 0.80. In summary, 99mTc-P483H safely, rapidly and accurately detected focal infection, was comparable with in vitro-labeled leukocyte imaging and therefore merits further investigation.

The utilization of technetium-99m CPI as a myocardial perfusion imaging agent in exercise studies.

Myocardial perfusion imaging with Tc-99m carbomethoxyisopropylisonitrile (CPI) was compared with Tl-201 imaging in 22 patients who were assessed for coronary artery disease. There was agreement between Tc-99m CPI and Tl-201 imaging for detecting segmental myocardial ischemia and fixed defects in 185/198 (93%) of left ventricular segments. There was also an excellent correlation between the two tracers for the detection of coronary artery disease (18/22 patients). Myocardial clearance of the isonitrile complex was slow, and there was no redistribution into ischemic regions; the normal to ischemic myocardial ratio remained relatively constant over time. Reinjection at rest was used to distinguish transient ischemia from infarction. The isonitrile complex was excreted rapidly via the hepatobiliary system. After 3 hours, background activity was reduced to about 20% of the initial activity. Tc-99m CPI appears comparable to Tl-201 thallous chloride for detecting coronary artery disease. Tc-99m CPI may be useful as a myocardial imaging agent because there is no myocardial redistribution, myocardial clearance is slow, and clearance from background tissues is rapid.

Chronic medication does not affect hyperactive error responses in obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) show an increased error-related negativity (ERN), yet previous studies have not controlled for medication use, which may be important given evidence linking performance monitoring to neurotransmitter systems targeted by treatment, such as serotonin. In an examination of 19 unmedicated OCD patients, 19 medicated OCD patients, 19 medicated patient controls without OCD, and 21 unmedicated healthy controls, we found greater ERNs in OCD patients than in controls, irrespective of medication use. Severity of generalized anxiety and depression was associated with ERN amplitude in controls but not patients. These data confirm previous findings of an exaggerated error response in OCD, further showing that it cannot be attributed to medication. The absence in patients of a relationship between ERN amplitude and anxiety/depression, as was found in controls, suggests that elevated error signals in OCD may be disorder-specific.