Plasma D-dimer: a useful tool for evaluating suspected pulmonary embolus.

Although ventilation-perfusion lung scanning is widely used in evaluating patients with suspected pulmonary embolus, additional rapid screening tests are needed to supplement scintigraphy in patients in whom the scan is indeterminate or the scan results are discordant with clinical suspicion. D-dimer is a fibrin degradation product which should be elevated in the presence of intravascular coagulation. We prospectively studied patients referred for lung scanning by obtaining a plasma D-dimer latex agglutination assay at the time of the scan. Of 64 patients who had pulmonary angiography to confirm the diagnosis, 16 were positive for pulmonary embolus and only one had a normal D-dimer. The D-dimer was normal in 27 of 48 patients without embolus and elevated in 21. Although an elevated D-dimer level is a nonspecific finding, we conclude that a normal D-dimer is a good negative predictor for pulmonary embolus, with a negative predictive value of 0.97.

SPECT imaging of fluorine-18.

UNLABELLED: The objective of this work was to determine the potential clinical usefulness of SPECT to image 511-keV annihilation photons. METHODS: A triple-headed gamma camera equipped with ultra-high-energy collimators was used to image 18F. Sensitivity measurements were carried out and the FWHM and FWTM were determined in air and for a unit-density scattering medium. Additionally, tomographic phantom studies were acquired to evaluate image quality. RESULTS: The sensitivities of the three cameras were, for all practical purposes, identical. At a source-to-collimator distance of 100 mm, the FWHM and FWTM were 13 and 29 mm, respectively. A tomographic phantom study demonstrated that spheres with a diameter of 20 mm were well resolved when filled with 18F activity and placed inside a water-filled phantom. CONCLUSION: The triple-headed SPECT camera in this investigation is a practical means of acquiring tomographic 18F images. The reconstructed slices were of sufficient quality to be of value in some clinical studies.

Radiolabeled iododeoxyuridine: safety evaluation.

UNLABELLED: The emphasis of radiolabeled iododeoxyuridine (*IUdR) research at our institution to date has been to assess its safety as a potential therapeutic agent. Toward this goal, we have performed preclinical and clinical studies, using various routes of administration, to detect adverse changes in normal tissues in both humans and animals. As IUdR is rapidly dehalogenated by the liver, the intravenous route is unlikely to be successful in therapeutic efforts. We have therefore focused our attention on more "protected" routes: intra-arterial and intravesicular administration. METHODS: Studies were performed in farm pigs after multiple administrations of [125I]IUdR into the aorta, carotid artery and bladder. IUdR and metabolites were measured in venous blood samples at appropriate time intervals after administration, after which histologic examination of tissues was performed. Studies in human have been performed after intra-arterial administration of [123I]IUdR in patients with liver metastases and intravesicular administration in patients with bladder carcinoma, initially using [123I]IUdR and currently using both [123I]IUdR and [125I]IUdR. Blood samples for pharmacokinetics and metabolite analysis and tissue for autoradiography (when feasible) have been obtained. RESULTS: To date, no evidence of adverse effects on normal tissue or alteration of hematologic or metabolic indices have been seen in pigs or humans. When instilled in the bladder, there is little leakage of IUdR in the circulation. CONCLUSION: When [125I]IUdR is used as a therapeutic agent, we anticipate little or no effect on normal tissues.

High affinity dopamine D2 receptor radioligands. 3. [123I] and [125I]epidepride: in vivo studies in rhesus monkey brain and comparison with in vitro pharmacokinetics in rat brain.

Studies of [123I]epidepride uptake in rhesus monkey brain were performed using single photon tomography. Striatal uptake peaked at 0.85% of administered dose/g at 107 min post-injection, then declined slowly to 0.70% of administered dose/g at 6 h. Striatal:posterior brain ratios rose from 2 at 25 min to 6.8 at 105 min, to 15 at 4 h and to 58 at 6.4 h. [123I]Epidepride was displaced by haloperidol (0.1 and 1 mg/kg) with a half-life of washout of 55 min. Little displacement of [123I]epidepride was observed following administration of 1 or 2 mg/kg d-amphetamine, respectively, indicating [123I]epidepride is not easily displaced by endogenous dopamine. In vitro equilibrium binding studies using rat striatum revealed a KD of 46 pM and Bmax of 33 pmol/g tissue at 37 degrees C, while at 25 degrees C the KD was 25 pM and the Bmax 32 pmol/g tissue. In vitro kinetic analysis of association and dissociation curves revealed a half-life for receptor dissociation at 37 degrees C of 15 min and 79-90 min at 25 degrees C. Allowing for the temperature difference, there is good correspondence between in vivo and in vitro dissociation kinetics at 25 degrees C. Increasing in vitro incubation temperature from 25 to 37 degrees C caused a 6-fold increase in the dissociation rate, suggesting that there is a change in binding kinetics at the dopamine D2 receptor at 37 degrees C compared to in vivo binding. The results of this study indicate that [123I]epidepride is an excellent radioligand for SPECT studies of the dopamine D2 receptor in man.

Gastric emptying and orocecal transit in portal hypertension and end-stage chronic liver disease.

Our aim was to evaluate gastric emptying and orocecal transit in patients with end-stage liver disease and portal hypertension undergoing evaluation for liver transplantation. Although gastric emptying half-times for both liquid and solid emptying were similar in patients with chronic liver disease and control subjects, orocecal transit, as measured by a scintigraphic technique, was significantly prolonged in the patients with liver disease (transit time, minutes, mean +/- SEM, patients versus controls: 127 +/- 10.5 versus 80 +/- 9.5, P < .003). Serum levels of progesterone and estradiol were similar in patients and controls. We conclude that small intestinal transit is delayed in patients with advanced liver disease and portal hypertension and may contribute to gastrointestinal symptoms and promote sepsis of enteric origin in this patient population.

Delayed gastric emptying of both the liquid and solid components of a meal in chronic liver disease.

OBJECTIVES: To evaluate gastric emptying in patients with chronic liver disease and portal hypertension. METHODS: We measured gastric emptying of both the liquid and solid components of a meal in 10 consecutive patients with chronic liver disease and portal hypertension, but free of ascites, and 14 age- and sex-matched healthy controls. In the patients with liver disease, relationships between emptying and liver function were examined. To measure gastric emptying, subjects consumed a test meal that consisted of scrambled eggs labeled with 99mTc-sulfur colloid and 4 oz of water labeled with 111In-diethylene triamine pentacetic acid (DTPA). RESULTS: Patients with liver disease and portal hypertension demonstrated delayed emptying of both the liquid (t1/2, min, mean +/- SE, patients vs. CONTROLS: 69.4 +/- 19.4 vs. 31.4 +/- 1.8, p < 0.01) and solid (post-lag phase solid emptying: 141 +/- 32.9 vs. 69.8 +/- 4.6, p < 0.006) components of the meal. We could not identify any correlation between gastric emptying and tests of liver function. CONCLUSIONS: Gastric emptying is delayed in patients with liver disease and portal hypertension; this abnormal gastric motor function may contribute to the pathophysiology of foregut complaints in this patient population.

Neuroradiologic applications of central nervous system SPECT.

Single photon emission computed tomography (SPECT) of the central nervous system (CNS) has many potentially useful interventional neuroradiologic applications. CNS SPECT allows easy and safe evaluation of the collateral circulation during internal carotid balloon test occlusion. The cerebrovascular distribution of intracarotid amobarbital sodium, which is used in the Wada test, can be accurately determined with simultaneous injection of a radiopharmaceutical. Easy and safe evaluation of the extent and distribution of vasospasm associated with subarachnoid hemorrhage or cerebral angiography is also possible with CNS SPECT. Images obtained after administration of acetazolamide can be compared with baseline images to evaluate cerebrovascular reserve before carotid endarterectomy. Seizure foci can be identified if peripheral intravenous injection is performed during an ictus. Thallium-201 imaging can be used to direct stereotactic brain biopsy to check for tumor recurrence. Radiologists need to familiarize themselves and their clinical colleagues with the many uses of this imaging technique.

Tumor localization and systemic absorption of intravesical instillation of radio-iodinated iododeoxyuridine in patients with bladder cancer.

PURPOSE: We evaluated tumor uptake and systemic distribution of intravesically instilled iododeoxyuridine (IUdR) in patients with superficial bladder cancer. MATERIALS AND METHODS: We performed 24 intravesical instillation studies in 11 patients with a mean age of 71 years. Radio-iodinated IUdR was administered through a Foley catheter. Gamma camera imaging was done after instillation and after 5 to 7 bladder irrigations. Tumor uptake was estimated by region of interest analysis. Bladder biopsy samples and surgical tumor specimens were tested for acid insoluble (deoxyribonucleic acid incorporated) radioactivity. Blood samples were obtained and analyzed for systemic absorption. RESULTS: Imaging was positive in all patients with bladder cancer. Average tumor uptake plus or minus standard deviation was 0.185+/-0.120% of the instilled dose. Preferential uptake of IUdR in the tumor was observed in all 6 patients undergoing tissue analysis. The tumor-to-normal bladder ratio ranged from 3.2 to 74,000 (median 202). Systemic absorption of IUdR was minimal. Blood sample analysis performed after intravesical instillation in all 11 cases revealed an average uptake of 3.2x10(-5)% instilled dose per ml. (range 0.69x10(-5) to 6.7x10(-5)) in the systemic circulation. Instillation within 24 hours after transurethral bladder tumor resection in 5 cases resulted in a higher but not dangerous average systemic uptake of 7.3x10(-4)% instilled dose per ml. (range 1.3x10(-5) to 2.6x10(-3)). Instillation 1 to 4 weeks after transurethral surgery in 8 cases resulted in no increased systemic absorption with an average blood level of 3.4+/-1.8x10(-5)% instilled dose per ml. There was no detectable distribution of radioactivity into other organs, including the thyroid. We noted no evidence of systemic toxicity in the study. CONCLUSIONS: Intravesical instillation of radio-iodinated IUdR achieves selective localization in the bladder tumor with minimal uptake by the normal bladder and minimal systemic absorption. The use of intravesical IUdR therapy for bladder cancer appears to be promising and requires further study.

On the safety of 5-[125I]iodo-2'-deoxyuridine--Preclinical evaluation in swine.

To increase tumor incorporation and minimize hepatic degradation of radio-IUdR, compartmental administration routes are being considered as an alternative to intravenous (i.v.) injections. Although there are significant data on the biodistribution and some reports on radiotoxicity of i.v.-administered 125IUdR, similar results for other routes of delivery are not available. We have undertaken a series of experiments intended to examine radiation effects of 125IUdR after intravesical (3 swine; eight 3 mCi doses at 4-day intervals), intracarotid (3 swine; two 10 mCi doses at 2-week intervals), and intra-aortic (5 swine, single dose of 10 mCi) administration in a swine model. Liver, renal functions, and complete blood counts were monitored throughout the duration of the experiment. Pharmacokinetics, systemic distribution of radioactivity and metabolites were measured. The normal tissue 125IUdR uptake and histology were determined after necropsy. No adverse systemic effects were identified. Clinical observations, laboratory data, and necropsy results were within normal range.