ABSTRACT
Medicine, including the pharmaceutical and biotechnology industries as well as many clinical practitioners, has recognized the importance of using molecular imaging biomarkers, including those labeled in such a way as to be imaged by positron emission tomography (PET), as tools for predicting outcomes in drug development and creating opportunities for "personalized" medicine, for diagnosing early-stage disease, and for the follow-up of the effectiveness of treatment.(1) However, only one important and widely used PET biomarker is currently approved by the Food and Drug Administration (FDA). If the technology is so important, we can ask why there is such a limitation to the availability of these biomarkers.
Subject(s)
Pharmacology, Clinical/methods , Positron-Emission Tomography/methods , Radioisotopes/chemistry , Radiopharmaceuticals/chemistry , Dideoxynucleosides/chemistry , Dideoxynucleosides/pharmacokinetics , Drug Approval , Fluorine Radioisotopes , Fluorodeoxyglucose F18/chemistry , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Misonidazole/chemistry , Misonidazole/pharmacokinetics , Molecular Structure , Nitriles/chemistry , Nitriles/pharmacokinetics , Radioisotopes/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , United States , United States Food and Drug AdministrationABSTRACT
As evidenced by the success of PET-CT, there are many benefits from combining imaging modalities into a single scanner. The combination of PET and MR offers potential advantages over PET-CT, including improved soft tissue contrast, access to the multiplicity of contrast mechanisms available to MR, simultaneous imaging and fast MR sequences for motion correction. In addition, PET-MR is more suitable than PET-CT for cancer screening due to the elimination of the radiation dose from CT. A key issue associated with combining PET and MR is the fact that the performance of the photomultiplier tubes (PMTs) used in conventional PET detectors is degraded in the magnetic field required for MR. Two approaches have been adopted to circumvent that issue: retention of conventional, magnetic field-sensitive PMT-based PET detectors by modification of other features of the MR or PET system, or the use of new, magnetic field-insensitive devices in the PET detectors including avalanche photo-diodes (APDs) and silicon photomultipliers (SiPMs). Taking the former approach, we are assembling a modified microPET Focus 120 within a gap in a novel, 1T superconducting magnet. The PMTs are located in a low magnetic field (approximately 30mT) through a combination of magnet design and the use of fiber optic 'bundles'. Two main features of the modified PET system have been tested, namely the effect of using long fiber optic bundles in the PET detector, and the impact of magnetic field upon the performance of the position sensitive PMTs. The design of a modified microPET-MR system for small animal imaging is completed, and assembly and testing is underway.
Subject(s)
Brain/pathology , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/instrumentation , Positron-Emission Tomography/methods , Animals , Electromagnetic Fields , Equipment Design , Image Enhancement , Image Interpretation, Computer-Assisted/methods , Magnetics , Mice , Phantoms, Imaging , Subtraction TechniqueABSTRACT
Avalanche photodiodes (APDs) have proven to be useful as light detectors for high resolution positron emission tomography (PET). Their compactness makes these devices excellent candidates for replacing bulky photomultiplier tubes (PMTs) in PET systems where space limitations are an issue. The readout of densely packed, 10 x 10 lutetium oxyorthosilicate (LSO) block detectors (crystal size 2.0 x 2.0 x 12 mm3) with custom-built monolithic 3 x 3 APD arrays was investigated. The APDs had a 5 x 5 mm2 active surface and were arranged on a 6.25 mm pitch. The dead space on the edges of the array was 1.25 mm. The APDs were operated at a bias voltage of approximately 380 V for a gain of 100 and a dark current of 10 nA per APD. The standard deviation in gain between the APDs in the array ranged from 1.8 to 6.5% as the gain was varied from 50 to 108. A fast, low-noise, multi-channel charge sensitive preamplifier application-specific integrated circuit (ASIC) was developed for the APD readout. The amplifier had a rise time of 8 ns, a noise floor of 515 e- rms and a 9 e- pF(-1) noise slope. An acquired flood image showed that all 100 crystals from the block detector could be resolved. Timing measurements with single-channel LSO-APD detectors, as well as with the array, against a plastic scintillator and PMT assembly showed a time resolution of 1.2 ns and 2.5 ns, respectively. The energy resolution measured with a single 4.0 x 4.0 x 10 mm3 LSO crystal, wrapped in four-layer polytetrafluoroethylene (PTFE) tape and coupled with optical grease on a single APD of the array, yielded 15% (full width at half maximum, FWHM) at 511 keV. Stability tests over 9 months of operation showed that the APD arrays do not degrade appreciably. These results demonstrate the ability to decode densely packed LSO scintillation blocks with compact APD arrays. The good timing and energy resolution makes these detectors suitable for high resolution PET.
Subject(s)
Equipment Failure Analysis , Gamma Cameras/veterinary , Lutetium/radiation effects , Positron-Emission Tomography/methods , Positron-Emission Tomography/veterinary , Radiometry/instrumentation , Silicates/radiation effects , Transducers , Equipment Design , Image Enhancement/instrumentation , Photochemistry/instrumentation , Radiation Dosage , Radiometry/methods , Radiometry/veterinary , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The count rate performance of the single LSO crystal layer high-resolution research tomograph (HRRT-S) PET scanner is limited by the processing speed of its electronics. Therefore, the feasibility of using an in-field-of-view (in-FOV) shield to improve the noise equivalent count rates (NECR) for small animal brain studies was investigated. The in-FOV shield consists of a lead tube of 12 cm length, 6 cm inner diameter and 9 mm wall thickness. It is large enough to shield the activity in the body of a rat or mouse. First, the effect of this shield on NECR was studied. Secondly, a number of experiments were performed to assess the effects of the shield on the accuracy of transmission scan data and, next, on reconstructed activity distribution in the brain. For activities below 150 MBq NECR improved only by 5-10%. For higher activities NECR maxima of 1.2E4 cps at 200 MBq and 2.2E4 cps at 370 MBq were found without and with shield, respectively. Listmode data taken without shield, however, were corrupted for activities above 75 MBq due to data overrun problems (time tag losses) of the electronics. When the shield was used data overrun was avoided up to activities of 150 MBq. For the unshielded part of the phantom, transmission scan data were the same with and without shield. The estimated scatter contribution was approximately 8.5% without and 5.5% with shield. Reconstructed emission data showed a difference up to 5% in the unshielded part of the phantom at 5 mm or more from the edge of the shielding. Of this 5% about 3% results from the difference in the uncorrected scatter contribution. In conclusion, an in-FOV shield can be used successfully in an HRRT PET scanner to improve NECR and accuracy of small animal brain studies. The latter is especially important when high activities are required for tracers with low brain uptake or when multiple animals are scanned simultaneously.
Subject(s)
Brain/diagnostic imaging , Equipment Failure Analysis/instrumentation , Image Enhancement/instrumentation , Tomography, Emission-Computed/instrumentation , Animals , Artifacts , Mice , Phantoms, Imaging , Quality Control , Rats , Reproducibility of Results , Sensitivity and Specificity , TransducersABSTRACT
As the use of high-throughput screening systems becomes more routine in the drug discovery process, there is an increasing need for fast and reliable analysis of the massive amounts of the resulting data. At the forefront of the methods used is data reduction, often assisted by cluster analysis. Activity thresholds reduce the data set under investigation to manageable sizes while clustering enables the detection of natural groups in that reduced subset, thereby revealing families of compounds that exhibit increased activity toward a specific biological target. The above process, designed to handle primarily data sets of sizes much smaller than the ones currently produced by high-throughput screening systems, has become one of the main bottlenecks of the modern drug discovery process. In addition to being fragmented and heavily dependent on human experts, it also ignores all screening information related to compounds with activity less than the threshold chosen and thus, in the best case, can only hope to discover a subset of the knowledge available in the screening data sets. To address the deficiencies of the current screening data analysis process the authors have developed a new method that analyzes thoroughly large screening data sets. In this report we describe in detail this new approach and present its main differences with the methods currently in use. Further, we analyze a well-known, publicly available data set using the proposed method. Our experimental results show that the proposed method can improve significantly both the ease of extraction and amount of knowledge discovered from screening data sets.
Subject(s)
Algorithms , Drug Evaluation, Preclinical/statistics & numerical data , Cluster Analysis , Data Interpretation, Statistical , Databases, Factual , Drug Design , Phylogeny , Structure-Activity RelationshipABSTRACT
The microPET Primate 4-ring system (P4) is an animal PET tomograph with a 7.8 cm axial extent, a 19 cm diameter transaxial field of view (FOV) and a 22 cm animal port. The system is composed of 168 detector modules, each with an 8 x 8 array of 2.2 x 2.2 x 10 mm3 lutetium oxyorthosilicate crystals, arranged as 32 crystal rings 26 cm in diameter. The detector crystals are coupled to a Hamamatsu R5900-C8 PS-PMT via a 10 cm long optical fibre bundle. The detectors have a timing resolution of 3.2 ns, an average energy resolution of 26%, and an average intrinsic spatial resolution of 1.75 mm. The system operates in 3D mode without inter-plane septa, acquiring data in list mode. The reconstructed image spatial resolution ranges from 1.8 mm at the centre to 3 mm at 4 cm radial offset. The tomograph has a peak system sensitivity of 2.25% at the centre of the FOV with a 250-750 keV energy window. The noise equivalent count rate peaks at 100-290 kcps for representative object sizes. Images from two phantoms and three different types of laboratory animal demonstrate the advantage of the P4 system over the original prototype microPET. including its threefold improvement in sensitivity and a large axial FOV sufficient to image an entire mouse in a single bed position.
Subject(s)
Tomography, Emission-Computed/instrumentation , Tomography, Emission-Computed/methods , Animals , Equipment Design , Image Processing, Computer-Assisted , Mice , Phantoms, Imaging , Reproducibility of Results , Time FactorsABSTRACT
PURPOSE: To compare combined whole-body PET and CT images of different cancers with PET images alone. MATERIALS AND METHODS: Thirty-two patients with known or possible cancers were examined using a combined positron emission tomographic (PET) and computed tomographic (CT) scanner. All data were acquired using this same combined scanner. After an injection of F-18 fluorodeoxyglucose (FDG), noncontrast helical CT imaging of the neck, chest, abdomen, or pelvis was performed. The spiral CT was followed by a PET scan covering the same axial extent as the CT. RESULTS: Coregistered PET-CT images identified and localized 55 lesions. In 10 patients (31%), areas with variable amounts of normal physiologic FDG uptake were distinguished from potential uptake of FDG in a nearby neoplastic lesion. Improved localization was achieved in 9 patients (for a total of 13 lesions, or 24%). CONCLUSION: Combined PET-CT images appear more effective than PET images alone to localize precisely neoplastic lesions and to distinguish normal variants from juxtaposed neoplastic lesions.
Subject(s)
Image Processing, Computer-Assisted , Neoplasms/diagnostic imaging , Tomography, Emission-Computed , Tomography, X-Ray Computed , Aged , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , RadiopharmaceuticalsABSTRACT
The 'EXACT3D' positron tomograph, which is now in routine clinical research use, was developed with the aim of achieving unprecedented sensitivity, high spatial and temporal resolution and simplicity of design using proven detector technology. It consists of six rings of standard detector blocks (CTI/Siemens EXACT HR+) with 4.39 mm x 4.05 mm x 30 mm elements, giving an axial field of view (FOV) of 23.4 cm. This extended FOV and the absence of interplane septa and retractable transmission rod sources has allowed greatly simplified gantry and detector cassette design. Operation in exclusive 3D mode requires an alternative to the conventional coincidence method for transmission scanning, and a single photon approach using a hydraulically driven 137Cs point source has been implemented. The tomograph has no other moving parts. A single time frame of data without any compression is very large (> 300 Mbyte) and two approaches are employed to overcome this difficulty: (a) adjacent sinograms can be summed automatically into different combinations and (b) listmode (event-by-event) acquisition has been instituted, which is both storage efficient (particularly for acquisition of sparse data sets) and maximizes temporal resolution. The high-speed I/O and computing hardware can maintain a sustained acquisition rate of about 4 million coincidence events per second. A disadvantage of the large axial FOV in 3D is the increased sensitivity to activity outside the coincidence FOV. However, this can be minimized by additional side shielding. The mean spatial resolution is 4.8 +/- 0.2 mm FWHM (transaxial, 1 cm off-axis) and 5.6 +/- 0.5 mm (axial, on-axis). Its absolute efficiency is 5.8% for a line source in air (just spanning the axial FOV) and 10% for a central point source (with thresholds of 350-650 keV). For a uniform 20 cm diameter cylinder, the efficiency is 69 kcps kBq(-1) ml(-1) (after subtraction of a scatter fraction of 42%). Sensitivity relative to the EXACT HR+ (with four rings of blocks) is 2.5 (3D) and 12 (2D) times respectively. The rate of random events in blood flow studies in the brain and body, using 15O-labelled water, can be controlled by limiting the administered dose and inserting additional side shielding.
Subject(s)
Phantoms, Imaging , Radioisotopes , Tomography, Emission-Computed/instrumentation , Tomography, Emission-Computed/methods , Cesium Radioisotopes , Equipment Design , Germanium , Humans , Iodine Radioisotopes , Reproducibility of Results , Scattering, Radiation , Sensitivity and Specificity , Thallium RadioisotopesABSTRACT
UNLABELLED: The availability of accurately aligned, whole-body anatomical (CT) and functional (PET) images could have a significant impact on diagnosing and staging malignant disease and on identifying and localizing metastases. Computer algorithms to align CT and PET images acquired on different scanners are generally successful for the brain, whereas image alignment in other regions of the body is more problematic. METHODS: A combined PET/CT tomograph with the unique capability of acquiring accurately aligned functional and anatomical images for any part of the human body has been designed and built. The PET/CT scanner was developed as a combination of a Siemens Somatom AR.SP spiral CT and a partial-ring, rotating ECAT ART PET scanner. All components are mounted on a common rotational support within a single gantry. The PET and CT components can be operated either separately, or in combined mode. In combined mode, the CT images are used to correct the PET data for scatter and attenuation. Fully quantitative whole-body images are obtained for an axial extent of 100 cm in an imaging time of less than 1 h. When operated in PET mode alone, transmission scans are acquired with dual 137Cs sources. RESULTS: The scanner is fully operational and the combined device has been operated successfully in a clinical environment. Over 110 patients have been imaged, covering a range of different cancers, including lung, esophageal, head and neck, melanoma, lymphoma, pancreas, and renal cell. The aligned PET and CT images are used both for diagnosing and staging disease and for evaluating response to therapy. We report the first performance measurements from the scanner and present some illustrative clinical studies acquired in cancer patients. CONCLUSION: A combined PET and CT scanner is a practical and effective approach to acquiring co-registered anatomical and functional images in a single scanning session.
Subject(s)
Neoplasms/diagnostic imaging , Tomography, Emission-Computed/instrumentation , Tomography, X-Ray Computed/instrumentation , Adult , Aged , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Data Interpretation, Statistical , Duodenal Neoplasms/diagnostic imaging , Equipment Design , Female , Fluorodeoxyglucose F18 , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Neoplasm Metastasis , Pancreatic Neoplasms/diagnostic imaging , Polyps/diagnostic imaging , Radiopharmaceuticals , Tomography, Emission-Computed/methods , Tomography, X-Ray Computed/methodsABSTRACT
A novel series of rigid P3-guanylpiperidine peptide mimics 3-14 was designed as potential factor Xa and prothrombinase inhibitors. Incorporation into a P2-gly-P1-argininal motif led to highly potent and selective inhibitors. The synthesis and biological activities of these derivatives are reported herein.
Subject(s)
Factor Xa Inhibitors , Guanine/pharmacology , Peptides/chemistry , Piperidines/pharmacology , Serine Proteinase Inhibitors/pharmacology , Cations , Guanine/analogs & derivatives , Guanine/chemistry , Guanine/pharmacokinetics , Molecular Mimicry , Piperidines/chemistry , Piperidines/pharmacokinetics , Serine Proteinase Inhibitors/chemistry , Serine Proteinase Inhibitors/pharmacokineticsABSTRACT
A novel scaffold for P4-P2 dipeptide mimics containing a rigid pyridone spacer was designed based on a virtual library strategy. Several selected nonpeptidic 4-aralkyl or 4-alkylpyridones incorporating a P1-argininal sequence were prepared. The modeling studies, synthesis and biological activities of these unique pyridone derivatives are reported herein.
Subject(s)
Arginine/chemistry , Pyridones/chemical synthesis , Thrombin/antagonists & inhibitors , Thrombin/chemistry , Factor Xa/pharmacology , Fibrinolysin/pharmacology , Inhibitory Concentration 50 , Kinetics , Models, Chemical , Trypsin/pharmacologyABSTRACT
Little is known about the relationship between teachers' family-of-origin variables, impacting their work attitudes and interpersonal skills, and students' academic outcome. This study investigated whether goodness of fit between teachers' and students' backgrounds is associated with subjective grading and objective achievement at school. One hundred one seventh graders and twenty of their teachers completed the Self-Report Family Inventory. Similarity between teachers' and students' work-culture variables was associated with the subjective grading practices of teachers. The self-report data also revealed effective teacher and successful student profiles.
Subject(s)
Achievement , Educational Measurement , Interpersonal Relations , Social Environment , Teaching , Adolescent , Analysis of Variance , Child , Female , Humans , Male , United StatesABSTRACT
A multi-centre project has been run to identify laboratory tests capable of predicting the leakage performance of disposable incontinence bedpads. Each of 95 subjects tested each of six products for a week in turn and reported whether or not they and/or their carers found the leakage performance of each product acceptable. In addition, carers noted the severity with which individual used bedpads had leaked so that, when they had been weighed, their leakage performance could be determined as a function of urine weight. These clinical data were compared with results from the 16 different laboratory tests used routinely for bedpad evaluation in three hospital laboratories. Each test was evaluated by seeing how well the data it yielded correlated with the clinical test data. No individual test was very successful at predicting the performance of bedpads when used as sole protection but a combination of an absorption capacity test and an absorption time test predicted the percentage of users/carers finding leakage performance acceptable, accurate to within +/- eight percentage points for all six test products. A different absorption capacity test proved most successful for bedpads used as back-up to body-worn products. It predicted the percentage of users/carers finding leakage performance acceptable, accurate to +/- five percentage points for all six products.
Subject(s)
Bedding and Linens , Disposable Equipment , Urinary Incontinence/therapy , Absorption , Bedding and Linens/statistics & numerical data , Disposable Equipment/statistics & numerical data , Equipment Design , Humans , Materials Testing/methods , Materials Testing/statistics & numerical data , Prognosis , United KingdomABSTRACT
An assay for the quantification of plasma and urine levels of CVS 1123, an orally bioavailable thrombin inhibitor, and its desmethyl form. CVS 738, was developed to support clinical and toxicology studies. This assay uses solid-phase extraction, reversed-phase HPLC separation, and post-column fluorescent derivatization with ninhydrin. An internal standard is added to correct for recovery. In aqueous solution, the arginine aldehyde structures of CVS 1123 and CVS 738 exist in multiple forms which can be separated under standard reversed-phase HPLC conditions. HPLC conditions were optimized to give rapid interconversion of the forms on the separation time scale, and consequently a single chromatographic peak. Extraction conditions were modified for quantitative extraction of drug compounds from large volumes of human plasma. The assay was shown to be accurate and precise, with a quantification limit of 17 ng CVS 1123/ml human plasma.
Subject(s)
Antithrombins/analysis , Arginine/chemistry , Chromatography, High Pressure Liquid/methods , Oligopeptides/analysis , Acetonitriles/chemistry , Animals , Antithrombins/chemistry , Antithrombins/urine , Arginine/analogs & derivatives , Chromatography, High Pressure Liquid/instrumentation , Esterases/blood , Esterases/metabolism , Humans , Hydrolysis , Indicators and Reagents/chemistry , Macaca fascicularis , Ninhydrin/chemistry , Oligopeptides/blood , Oligopeptides/chemistry , Oligopeptides/urine , Rats , Reproducibility of Results , Sensitivity and Specificity , Spectrometry, Fluorescence , Temperature , Trifluoroacetic Acid/chemistryABSTRACT
The N-terminal thrombin receptor peptide H-Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe-OH (1) fully activates the thrombin receptor with an EC50 of 10 microM. Structural features in the tetradecapeptide which are responsible for receptor activation have been elucidated. Agonist potency has been enhanced 1000-fold with the design of the shortened peptide H-Ala-Phe(p-F)-Arg-Cha-HArg-Tyr-NH2 (56). This analog exhibits an EC50 of 0.01 microM and is the most potent agonist for receptor activation reported to date. The monoiodinated derivative H-Ala-Phe(p-F)-Arg-Cha-HArg-Tyr(3-I)-NH2 (59) exhibits an EC50 of 0.03 microM, a level sufficient for development of a radioligand.
Subject(s)
Oligopeptides/pharmacology , Receptors, Thrombin/agonists , Amino Acid Sequence , Humans , Ligands , Molecular Sequence Data , Structure-Activity RelationshipABSTRACT
BACKGROUND: Thrombin inhibitors have been shown to be efficacious in animal models of thrombosis and in initial human clinical trials. It is unknown if their efficacy is due to their prevention of thrombin-mediated fibrin formation or to an inhibitory effect on thrombin-stimulated platelet activation. Appropriate tools to address this question have not been available. Therefore, to evaluate the role of the platelet thrombin receptor in intravascular thrombus formation, a polyclonal antibody was raised against a peptide derived from the thrombin-binding exosite region of the cloned human thrombin receptor. This antibody serves as a selective inhibitor of the thrombin receptor for in vivo evaluation. METHODS AND RESULTS: The immune IgG (IgG 9600) inhibited thrombin-stimulated aggregation and secretion of human platelets. In contrast, it had no effect on platelet activation induced by other agonists including ADP, collagen, or the thrombin receptor-derived peptide SFLLR-NH2. IgG 9600 also inhibited thrombin-induced aggregation of African Green monkey (AGM) platelets. By Western blot analysis, the IgG identified a protein of approximately 64 kD in homogenates of both human and AGM platelets. The effect of thrombin receptor blockade by this antibody on arterial thrombosis was evaluated in an in vivo model of platelet-dependent cyclic flow reductions (CFRs) in the carotid artery of the AGM. The intravenous administration of IgG 9600 (10 mg/kg) abolished CFRs in three monkeys and reduced CFR frequency by 50% in a fourth monkey. Ex vivo platelet aggregation in response to up to 100 nmol/L thrombin was completely inhibited during the 120-minute postbolus observation period in all four animals. There was a twofold increase in bleeding time, which was not statistically different from baseline, and ex vivo clotting time (APTT) was not changed. The glycoprotein IIb/IIIa receptor antagonist MK-0852 and the thrombin inhibitor recombinant hirudin also demonstrated inhibitory effects on CFRs at doses that did not significantly prolong template bleeding time. Control IgG had no effect on CFRs, ex vivo platelet aggregation, bleeding time, or APTT. CONCLUSIONS: These results demonstrate that blockade of the platelet thrombin receptor can prevent arterial thrombosis in this animal model without significantly altering hemostatic parameters and suggest that the thrombin receptor is an attractive antithrombotic target.
Subject(s)
Antibodies/therapeutic use , Receptors, Thrombin/immunology , Thrombosis/drug therapy , Animals , Antibody Formation , Chlorocebus aethiops , Platelet Aggregation/drug effects , Receptors, Thrombin/chemistry , Receptors, Thrombin/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/immunologyABSTRACT
The aggregation of platelets from a variety of animal species in response to thrombin receptor-derived activating peptides was evaluated. A series of 14-(SFLLRNPNDKYEPF), 7-(SFLLRNP-NH2), 6-(SFLLRN-HN2) or 5-(SFLLR-NH2) residue peptides, the structures of which were based on the deduced amino acid sequence of the human thrombin receptor, promoted full aggregation of platelets in plasma from humans, African Green and Rhesus monkeys, baboons and guinea pigs at 4-50 microM depending on the peptide used. Platelets in plasma from rabbit, dog, pig, and hamster underwent a shape change but failed to aggregate in response to these peptides over 3 log units of peptide up to 800 microM, despite being fully responsive to human thrombin. However, because the receptor peptides induced shape change in the platelets from these non-aggregating species, they apparently can activate some of the intracellular signaling system(s) usually initiated by thrombin in these platelets. In contrast, platelets from rats did not undergo shape change or aggregate in response to the peptides. A 7-residue receptor-derived peptide based on the deduced amino acid sequence of the clone of the hamster thrombin receptor (SFFLRNP-N2) was nearly as efficacious as the corresponding human receptor-derived 7-residue peptide to promote aggregation of human platelets. However, the hamster peptide could not promote aggregation of hamster platelets in plasma at up to 800 microM peptide, while a shape change response was elicited. Platelets from rats, rabbits and pigs also did not aggregate in response to this peptide derived from the hamster thrombin receptor, but all species except the rat underwent a shape change.(ABSTRACT TRUNCATED AT 250 WORDS)