Phase II study of treatment of advanced ovarian cancer with folate-receptor-targeted therapeutic (vintafolide) and companion SPECT-based imaging agent (99mTc-etarfolatide).

BACKGROUND: This report examines (99m)Tc-etarfolatide imaging to identify the presence of folate receptor (FR) on tumors of women with recurrent/refractory ovarian or endometrial cancer and correlates expression with response to FR-targeted therapy (vintafolide). PATIENTS AND METHODS: In this phase II, single-arm, multicenter study, patients with advanced ovarian cancer were imaged with (99m)Tc-etarfolatide before vintafolide treatment. Up to 10 target lesions (TLs) were selected based on Response Evaluation Criteria In Solid Tumors criteria using computed tomography scans. Single-photon emission computed tomography images of TLs were assessed for (99m)Tc-etarfolatide uptake as either FR positive or negative. Patients were categorized by percentage of TLs positive and grouped as FR(100%), FR(10%-90%), and FR(0%). Lesion and patient response were correlated with etarfolatide uptake. RESULTS: Forty-nine patients were enrolled; 43 were available for analysis. One hundred thirty-nine lesions were (99m)Tc-etarfolatide evaluable: 110 FR positive and 29 FR negative. Lesion disease control rate (DCR = stable or response) was observed in 56.4% of FR-positive lesions versus 20.7% of FR-negative lesions (P < 0.001). Patient DCR was 57%, 36%, and 33% in FR(100%), FR(10%-90%), and FR(0%) patients, respectively. Median overall survival was 14.6, 9.6, and 3.0 months in FR(100%), FR(10%-90%), and FR(0%) patients, respectively. CONCLUSIONS: Overall response to FR-targeted therapy and DCR correlate with FR positivity demonstrated by (99m)Tc-etarfolatide imaging. CLINICAL TRIAL NUMBER: NCT00507741.

Regional gastric emptying abnormalities in functional dyspepsia and gastro-oesophageal reflux disease.

To characterize proximal and distal stomach emptying in functional dyspepsia (FD) and gastro-oesophageal reflux disease (GORD). Eighty-three patients underwent gastric emptying (GE) scintigraphy and symptom scoring for the evaluation of upper gastrointestinal symptoms and were divided into three groups: FD (n = 25), GORD (n = 20) and FD + GORD (n = 38). Total, proximal and distal gastric retention were determined scintigraphically and compared with normal controls. Delayed total GE was observed in each subgroup: FD (56%), GORD (45%) and FD + GORD (55%). Greater proximal gastric retention was observed after meal ingestion in GORD compared to FD. Greater distal gastric retention was observed in FD and FD + GORD but it was only mild in GORD. Nausea, vomiting, early satiety, distention and regurgitation were associated with proximal gastric retention whereas there was no symptom associated with distal gastric retention. Multiple regression demonstrated total gastric retention at 30 min and 1 h was positively correlated with regurgitation whereas early proximal gastric retention was positively correlated with regurgitation and negatively correlated with nausea. Selective abnormalities of proximal and distal stomach emptying were demonstrated in GORD and FD. GORD and FD symptoms were associated with proximal gastric retention suggesting that proximal stomach motor function may be important in the pathogenesis of symptoms associated with these disorders.

Binding properties of 111In-diethylenetriaminepentaacetic acid (DTPA)-fragment E1,2, a fibrin-specific probe, are dependent on use of protecting complex during attachment of DTPA groups.

Fragments E1 and E2, plasmic degradation products of crosslinked fibrin, bind specifically to polymers of fibrin. A mixture of these fragments, denoted as fragment E1,2, was radiolabeled with 111In after covalently attaching metal chelating groups (diethylenetriaminepentaacetic acid, DTPA) to the fragment, using two approaches. In the first approach, DTPA groups were attached directly to purified fragment E1,2. In the second approach, attachment sites of DTPA groups were directed away from the active region of the molecule by having fragment E1,2 bound in complex, with its active sites protected during the derivatization. Direct attachment of DTPA groups to fragment E1,2 resulted in complete loss of binding to fibrin in vitro. When derivatized in complex, 111In-DTPA-fragment E1,2 retained a higher degree of binding to human fragment DD and human plasma clots in vitro than did radioiodinated fragment E1, even when up to eight DTPA groups were attached per molecule of fragment E1,2.

Bone mineral density in postmenopausal women treated with L-thyroxine.

PURPOSE: To determine if bone mineral density is decreased in postmenopausal women treated with 1-thyroxine, and, if any decrease is observed, whether it is related to overtreatment with thyroid hormone, to deficiency of calcitonin, or to other factors. PATIENTS AND METHODS: The study consisted of 19 postmenopausal women between 50 and 75 years of age treated with 1-thyroxine for 5 years or longer, and 19 matching control subjects with no thyroid disease. Bone mineral density of the spine and hip was measured by dual-photon absorptiometry. Plasma calcitonin concentrations and serum thyroid hormone levels were determined by radioimmunoassays. RESULTS: The 1-thyroxine-treated women had lower bone density in the lumbar spine (1.013 g/cm2 [95% confidence interval, 0.945 to 1.081] versus 1.134 g/cm2 [1.026 to 1.242], p = 0.043); in the femoral neck (0.736 g/cm2 [0.694 to 0.778] versus 0.809 g/cm2 [0.747 to 0.872], p = 0.040); in Ward's triangle (0.576 g/cm2 [0.530 to 0.623] versus 0.694 g/cm2 [0.617 to 0.770], p = 0.011); and in the trochanteric area (0.626 g/cm2 [0.581 to 0.672] versus 0.722 g/cm2 [0.651 to 0.794], p = 0.027). The maximal increase in calcitonin following calcium infusion was 1.37 ng/L (95% confidence interval, -0.44 to 3.17) in the 1-thyroxine-treated patients versus 18.8 ng/L (95% confidence interval, 10.0 to 27.5) in normal women, p less than 0.001. The average dose of 1-thyroxine was 120 micrograms/day; 16 of the 19 patients had normal serum thyroxine levels. However, TSH levels were low in 13 of the 19, suggesting that 1-thyroxine treatment was supraphysiologic. Seven of the 19 patients had a history of hyperthyroidism in the distant past; these patients, considered separately, had significantly reduced bone density in the hip. The other 12 patients, considered separately, did not have a statistically significant loss of bone density. CONCLUSIONS: Long-term 1-thyroxine therapy is associated with decreased density of the spine and hip. Since subclinical hyperthyroidism, decreased calcitonin responsiveness, and a history of hyperthyroidism were demonstrated in some or all of these patients, these factors must be considered as possible causes of the decreased bone density.

Soft-tissue uptake of technetium-99m-MDP after prostate cryoablation.

Prominent soft-tissue uptake of 99mTc-methylene diphosphonate (MDP) within the prostate bed was found after cryoablation for prostate carcinoma. CT, MRI and sonographic studies demonstrated liquifactive necrosis of the prostate bed. The probable etiology for 99mTc-MDP uptake in this case is necrosis with subsequent neovascular hyperemia and microscopic calcium deposits. Three-phase scintigraphy with 99mTc-MDP appears to be useful for localizing the extent of soft tissue inflammation and necrosis.

Comparison of iodine-123-disintegrins for imaging thrombi and emboli in a canine model.

UNLABELLED: Disintegrins are peptides found in viper venoms which bind to platelets through the glycoprotein IIb-IIIa receptor. The purpose of this work was to evaluate the ability of disintegrins to image thrombi and emboli in vivo. METHODS: Eight disintegrins (bitistatin, albolabrin, echistatin, eristostatin, kistrin, mambin, halysin and barbourin) were purified from snake venom. After radiolabeling with 123I, disintegrins were tested for their ability to image 24-hr-old experimental deep vein thrombi (DVT) and pulmonary emboli in a canine model. Labeled fibrinogen and platelets were used as controls. Gamma camera imaging was performed during the first 4 hr, after which tissue samples were collected for counting. RESULTS: Of the disintegrins tested, 123I-bitistatin had higher uptake in DVT (0.21 +/- .06% ID/g) than any other disintegrin (0.009-0.036%/g, p < 0.05). Bitistatin had higher DVT-to-blood ratios (9.8 +/- 2.5) than all other disintegrins, 125I-fibrinogen or 99mTc-HMPAO-platelets (p < 0.05). Images of DVT obtained with 123I-bitistatin were focally positive within 1 hr and improved by 4 hr. In pulmonary emboli, the absolute uptake of 123I-bitistatin (0.64 +/- 0.17% ID/g) was higher than all other compounds (p < 0.05), although barbourin had moderate uptake (0.23 +/- 0.11% ID/g) and may also be useful for imaging pulmonary embolism (PE). The uptake of bitistatin in PE was superior to both 125I-fibrinogen (0.18 +/- 0.02% ID/g) (p < 0.05) and 99mTc-HMPAO-platelets (0.14 +/- 0.02% ID/g, p < 0.05). Iodine-123-bitistatin had embolus-to-blood ratios averaging 27 +/- 7, which was higher than platelets, fibrinogen, echistatin, mambin or halysin (p < 0.05). Iodine-123-bitistatin background in lungs, liver and heart were low, which permitted visualization of all pulmonary emboli by 2-4 hr after injection. CONCLUSION: Labeled bitistatin should be investigated further as an agent which may permit rapid imaging of both thrombi and emboli.

Opioid and opioid-like drug effects on whole-gut transit measured by scintigraphy.

UNLABELLED: We studied the effects of several drugs on gastrointestinal transit (tramadol HCl, acetaminophen with codeine and placebo) in a randomized, double-blind, crossover study. METHODS: Combined gastric emptying, small bowel and colonic transit scintigraphy was performed in 12 normal subjects. Each subject received a standardized diet and study drug on Days 1-5. On Day three, subjects received a radiolabeled solid and liquid phase meal. RESULTS: No significant difference in the gastric T1/2 (mean +/- s.e.m.) of solids for placebo (69 +/- 7 min), APAP/C (74 +/- 15 min) or tramadol (686 +/- 8 min) (p = 0.86) were seen. Similarly there was no significant difference in the T1/2 of liquids for placebo (31 +/- 4 min), APAP/C (41 +/- 6 min) (p = 0.29). Orocecal transit times were not significantly different for placebo (237 +/- 20 min), APAP/C (311 +/- 26 min) or tramadol (311 +/- 10 min) (p = 0.12). Colon geometric centers (GC) for placebo at 24, 48 and 72 hr were 4.6 +/- 0.35, 6.0 +/- 0.28 and 6.8 +/- 0.08. The GC for tramadol and APAP/C were all significantly lower at 72 hr, 6.4 +/- 0.17 and 6.2 +/- 0.17, respectively compared to the placebo. The GC of tramadol at 24 and 48 hr (3.8 +/- 0.4, 5.4 +/- 0.26) were not significantly different from placebo. In contrast, the GC for APAP/C at 24 and 48 hr (3.3 +/- 0.31, 5.0 +/- 0.26) were significantly delayed. All subjects recorded a significant increase in constipation on drugs compared to placebo (p = 0.04). CONCLUSION: Tramadol and APAP/C had no effect on gastric emptying or small bowel transit. At equianalgesic doses, tramadol caused less delay in colonic transit than APAP/C for 48 hr and delay in the GC agreed with the subjective complaints of constipation on both drugs.

The buildup factor: effect of scatter on absolute volume determination.

We have developed a new method for generating attenuation-corrected images for use in absolute volume and activity measurements. The technique relies on the use of a set of measured buildup factors to correct for the effects of scatter inherent in the broad-beam conditions of clinical nuclear medicine and requires anterior and posterior count-rate measurements. The scatter correction requires that the well-known attenuation factor e-mud be replaced by 1-(1-e-mud)B(infinity), where B(infinity) is the buildup factor at infinite depth. The buildup factors for four different scintillation camera window settings and three different source sizes are reported. The method was validated by calculating phantom volumes and comparing the results to a previously reported technique which does not account for the scatter contribution by assuming mu = 0.15 cm-1. The results showed that the buildup factor method provides less than 7.3% error for volume determinations at all investigated depths, window settings, and source sizes, whereas errors of 3.3-26.7% were found with the other technique.

Evaluation of indium-111-labeled anti-fibrin antibody for imaging vascular thrombi.

Monoclonal antibody 59D8 developed by Hui et al., binds to fibrin but not fibrinogen. An 111In-labeled Fab fragment of 59D8 was studied in vitro and in animal models to evaluate its potential for imaging thrombi and emboli in man. Rabbits and dogs were used as models for studying thrombus uptake in vivo. Thrombi and emboli up to 4 days old were successfully visualized at 4-24 hr postinjection in five of eight rabbits. In dogs, 0.5-hr-old and 24-hr-old thrombi were successfully imaged at 24 hr in six of eight animals, and 3/6 of these were positive at 3-4 hr postinjection. Thrombus-to-blood ratios in the dogs averaged 7.1 +/- 1.3. The findings suggest this antibody may be useful for imaging thrombi in man.

Imaging pulmonary emboli and deep venous thrombi with 99mTc-bitistatin, a platelet-binding polypeptide from viper venom.

UNLABELLED: An imaging test that could locate both pulmonary emboli (PE) and their source, active deep venous thrombi (DVT), would be valuable in patient management. Bitistatin, an 83-amino-acid polypeptide isolated from Bitis arietans venom, binds avidly to the glycoprotein IIb/IIIa receptor on platelets. The goal of this study was to label bitistatin with 99mTc and assess its potential for imaging thrombi and emboli in vivo. METHODS: Molecular modeling of bitistatin indicated that its primary amines are located on the opposite side of the molecule from the receptor-binding domain. The primary amines were reacted with succinimidyl-4-hydrazino nicotinate hydrochloride to place 2.4 hydrazino nicotinate (Hn) chelating groups per peptide molecule. Hn-bitistatin was labeled by incubation with 99mTc-glucoheptonate to 96 TBq/mmol and then tested for binding to platelets in vitro and for imaging of 24-h-old DVT and PE in a canine model used previously for other thrombus tracers. RESULTS: 99mTc-Hn-bitistatin bound to stimulated platelets with a dissociation constant (Kd) = 32 nmol/L, similar to that of 125I-bitistatin (Kd = 41 nmol/L). In vivo, focal uptake was observed in planar images as early as 30 min (DVT) and 60 min (PE) after injection. Lesion uptake of 99mTc-Hn-bitistatin at 4 h after injection was calculated in terms of percentage injected dose per gram (%ID/g) of tissue and averaged 0.89 %ID/g PE and 0.79 %ID/g DVT. Lesion-to-background ratios averaged 34:1 (PE-to-lung), 18:1 (DVT-to-blood), and 284:1 (DVT-to-muscle). These values were not significantly different from iodinated bitistatin, but uptakes were higher than other tracers tested in the same model. CONCLUSION: 99mTc-Hn-bitistatin retains the functional activity of the iodinated peptide, has higher DVT and PE uptakes than other thrombus tracers in this standardized model, and has target-to-background characteristics suitable for imaging both PE and DVT in a single test.

SPECT quantification of cerebral ischemia before and after carotid endarterectomy.

A method to assess changes in cerebral perfusion following carotid endarterectomy was developed using late (2 hr)/early (20 min) single-photon emission computed tomography (SPECT)/[123I]iodoamphetamine count ratios. Using a ratio greater than 1.0 to indicate redistribution and reversible ischemia, pre- and postoperative studies were compared for 20 patients. Regional polar plots based on 30 degrees angular sectors showed improvement greater than 2 standard deviations (s.d.s) ipsilateral to surgery in 15/19 (79%) and contralateral to the side of surgery in 8/19 (42%) patients with significant hemodynamic lesions. Using a hemispheric perfusion index (mean of four 30 degrees sectors) ipsilateral perfusion improved in 11/19 (58%) with bilateral improvement in 6/19 (32%). Visual interpretation was similar to the regional analysis with 14/19 (74%) improving on the operative side; however, it was less sensitive for contralateral changes, 4/19 (21%). We conclude that quantitation of redistribution can provide an objective index of improved perfusion and is especially important to detect contralateral changes.

Thrombus imaging with technetium-99m synthetic peptides based upon the binding domain of a monoclonal antibody to activated platelets.

UNLABELLED: Monoclonal antibodies which recognize fibrin or platelets have enabled imaging of vascular thrombi, however, early imaging has been difficult because of the slow blood disappearance of even small antibody fragments. It was theorized that it might be possible to synthesize peptides which possess the same thrombus affinity as monoclonal antibodies, but which would leave the blood pool much more rapidly. METHODS: In this study, peptides were synthesized with amino acid sequences based on the primary binding region of the platelet glycoprotein IIb/IIIa-directed monoclonal antibody PAC1. Both termini of the peptides were blocked to prevent rapid proteolysis and a metallothionein-derived sequence was incorporated as a chelating agent for reduced technetium. RESULTS: Technetium-99m-labeled peptides produced images of fresh clots in the jugular veins of rabbits and day-old thrombi in the femoral veins of dogs within 2 hr after injection. In control experiments, a 99mTc-labeled nonspecific peptide failed to produce focal images of thrombus. Another control compound, 99mTc-glucoheptonate, did produce images of fresh clots in rabbits but failed to produce focal images of day-old thrombi. As was hoped, blood clearance of the 99mTc peptides was rapid, with excretion through the kidneys, however, none of the peptides studied had better thrombus-to-blood ratios than iodinated fibrinogen and all had significantly lower deposition in the thrombus. CONCLUSION: Using labeled synthetic peptides appears to be technically feasible but the absolute binding to thrombus is not yet sufficient for reliable imaging of pre-existing thrombi.

Comparison of left anterior oblique and geometric mean gastric emptying.

A left anterior oblique image (LAO) and the geometric mean of anterior and posterior counts have both been proposed as methods for acquiring gastric emptying data. Both approaches are used to correct for the changes in attenuation that occur as the depth of radiolabeled solids changes during gastric emptying. These two methods were compared by using a power exponential curve fit to calculate a lag phase, an equilibrium emptying rate, and a half-time for gastric emptying in 20 patients. There were no significant differences (mean +/- 1 s.e.m.) in the measured half-emptying time (115 +/- 10 versus 104 +/- 7 min) (p = 0.08) or rate of gastric emptying (0.015 +/- 0.002 versus 0.015 +/- 0.002 min-1) (p = 0.56) for LAO imaging versus the geometric mean. However, the LAO measurements of the lag phase were significantly higher (69 +/- 7 min) than the geometric mean (53 +/- 6 min) measurements (p = 0.004). This resulted in 4/20 (20%) of patients with normal geometric mean lag phase measurements who would have been reclassified as abnormal using the LAO method.

SPECT in patients with cortical visual loss.

Single-photon emission computed tomography (SPECT) with 99mTc-hexamethylpropyleneamine oxime (HMPAO) was used to investigate changes in cerebral blood flow in seven patients with cortical visual impairment. Traumatic brain injury (TBI) was the cause of cortical damage in two patients, cerebral ischemia in two patients and carbon monoxide (CO) poisoning, status epilepticus and Alzheimer's Disease (AD) each in three separate patients. The SPECT scans of the seven patients were compared to T2-weighted magnetic resonance image (MRI) scans of the brain to determine the correlation between functional and anatomical findings. In six of the seven patients, the qualitative interpretation of the SPECT studies supported the clinical findings (i.e., the visual field defect) by revealing altered regional cerebral blood flow (rCBF) in the appropriate regions of the visual pathway. MR scans in all of the patients, on the other hand, were either normal or disclosed smaller lesions than those detected by SPECT. We conclude that SPECT may reveal altered rCBF in patients with cortical visual impairment of various etiologies, even when MRI studies are normal or nondiagnostic.

Preparation and preliminary evaluation of technetium-99m-labeled fragment E1 for thrombus imaging.

Fragment E1 labeled with 123I has been previously shown to permit imaging of thrombi in patients within as little as 20 min after injection. Because of the relatively rapid localization and blood disappearance of this protein, 99mTc would be the most clinically acceptable radionuclide for labeling Fragment E1. In this study, human fragment E1 was derivatized with a hydrazino nicotinate function to permit radiolabeling with reduced technetium. The modification reaction was carried out while the fragment E1 was protected in a complex, so that the modification occurred in nonfunctional regions of the fragment E1 molecule. After radiolabeling with 99mTc, the modified fragment E1 retained its functional activity, as judged by its binding to fragment DD in vitro. The ability of 99mTc-fragment E1 to produce images of venous thrombi was demonstrated in animal models. Images were focally positive within 20 min to 1 hr after injection. Thrombus-to-blood ratios exceeded those from 125I-fibrinogen in the same animals. This method of labeling appears to provide an alternative radiolabel to 123I without compromising the function of fragment E1.

Limitations of craniocaudal thallium-201 and technetium-99m-sestamibi mammoscintigraphy.

UNLABELLED: Previous studies with 201Tl and 99mTc-sestamibi (MIBI) have used large field of view (LFOV) cameras not optimized for breast imaging. The purpose of this study was to compare these agents and to determine if a small field of view (SFOV) camera designed to minimize the camera-to-breast distance could improve tumor detection. METHODS: A 28-cm (SFOV) camera was fitted with slant-hole and diverging collimators to perform craniocaudal scintigraphy for direct comparison with mammography. Of the 46 patients studied, 20 had 201Tl imaging alone and 26 had combined 201Tl and MIBI imaging. LFOV (40 cm) breast and axillary images also were obtained. Visual and quantitative analyses of tumor uptake were performed. RESULTS: The SFOV camera with nonparallel collimation showed variable 201Tl and MIBI normal breast activity. This was partly due to significant scatter from cardiac and abdominal activity. Overall, 201Tl had a sensitivity of 53%, which was 67% for tumors > or = 1.5 cm and 20% for tumors < or = 1.5 cm. MIBI sensitivity was 90% (9/10) for lesions > or = 1.5 cm. Specificity was 93% for 201Tl and 83% for MIBI. There was no significant difference in 201Tl (1.76 +/- 0.55) and MIBI (1.82 +/- 0.95) tumor uptake ratios (p = 0.75). CONCLUSION: Technetium-99m-MIBI was more sensitive than 201Tl for imaging lesions > or = 1.5 cm. Craniocaudal positioning minimized the camera-to-breast distance but did not increase 201Tl detection of tumors < 1.5 cm and increased background breast activity due to scatter.

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.

Utility of three-phase skeletal scintigraphy in suspected osteomyelitis: concise communication.

Three-phase skeletal scintigraphy, consisting of a radionuclide angiogram, an immediate postinjection "blood-pool" image, and 2--3 hr delayed images, was performed on 98 patients with suspected osteomyelitis. This procedure was evaluated by first interpreting only the delayed images, next the combination of "blood-pool" and delayed images, and finally the three-phase study. There was no change in the sensitivity (12/13 = 0.92) for detecting osteomyelitis, but the false-positive rate for osteomyelitis decreased from 0.25 (21/85) to 0.06 (5/85). In 21 of 64 patients (33%) with abnormal studies, the "blood-pool" image and/or the radionuclide angiogram led to a more accurate scintigraphic diagnosis. In 12 patients (19%) the "blood pool" alone was enough to achieve the correct final diagnosis and was used most often to identify noninfectious skeletal disease. In 9 patients (14%) the radionuclide angiogram was required for an accurate interpretation and was considered essential most often in cases of soft-tissue infection. Both radionuclide angiography and "blood-pool" imaging appear to augment the specificity of skeletal scintigraphy in patients with suspected osteomyelitis.

In vitro platelet binding compared with in vivo thrombus imaging using alpha(IIb)beta3-targeted radioligands.

Radioligands for the alpha(IIb)beta3 integrin on platelets are being studied for their ability to image venous thrombi and pulmonary emboli. One such radioligand, 123I-bitistatin, was previously shown to have higher thrombotic uptake in an animal model than other disintegrins, but the reason for this difference was not clear. The purpose of this study was to evaluate three labeled disintegrins, bitistatin, kistrin and barbourin, to look for in vitro differences in platelet binding which could explain the in vivo behavior. Disintegrins labeled with 121I were compared in vitro for extent of binding to platelets and rates of binding and dissociation. These findings were related to organ distribution and image quality for imaging thrombotic lesions, following administration of 123I-disintegrins in an animal model. Fibrinogen at 8.8 micromol/l was able to displace 125I-barbourin and 125I-kistrin more rapidly from ADP-stimulated platelets, with half-times of 3.5 and 10.7 min, compared with 125I-bitistatin (31.6 min). At equivalent concentrations in whole blood, a higher percentage of bitistatin bound to platelets compared with the other two. In vivo, kistrin and barbourin had significantly lower thrombus:muscle and pulmonary embolus:lung ratios in images compared with bitistatin. There was evidence of more metabolic deiodination of labeled kistrin and barbourin in vivo compared with bitistatin. A surprising finding was that conventional in vitro platelet binding studies did not predict the relative in vivo behavior of labeled disintegrins. The results suggest that labeled bitistatin has improved targeting of thrombi because it is less easily displaced from stimulated platelets, permitting longer lesion retention. It also appears to have a greater association with resting platelets in the blood, which may increase bioavailability and delay metabolic breakdown.

Absolute left ventricular volume from gated blood pool imaging with use of esophageal transmission measurement.

A new method for determining absolute left ventricular (LV) volume from equilibrium gated blood pool images was validated in 36 patients by comparing gated blood pool (GBP) imaging with contrast ventriculography (CV) using both Simpson's rule (SR) and area-length (AL) calculations. The technique is geometry-independent and is the first to correct for tissue attenuation with use of an in vivo point source. An orally administered capsule containing 1 to 2 mCi of technetium-99m (Tc-99m) sulfur colloid is used for this purpose. Left ventricular volumes are determined by dividing attenuation and background-corrected count rates obtained from semiautomated LV regions of interest by the count rate per milliliter from a blood sample. The correlation between GBP and CV (SR) was 0.96 (CV [SR] = 0.99 GBP + 1.32 ml; standard error of the estimate [SEE] = 21.2 ml) for diastole and 0.97 (CV [SR] = 0.93 GBP - 0.03 ml; SEE = 11.9 ml) for systole. The correlation between GBP and CV (AL) was 0.92 (CV [AL] = 0.90 GBP + 16.72 ml; SEE = 27.8 ml) for diastole and 0.95 (CV [AL] = 0.87 GBP + 4.56 ml; SEE = 14.4 ml) for systole. The method is noninvasive and can be performed easily as part of routine gated blood pool imaging and analysis.