Bruce J. Barron

Yttrium 90 Resin Microspheres for the Treatment of Unresectable Colorectal Hepatic Metastases after Failure of Multiple Chemotherapy Regimens: Preliminary Results

PURPOSE Responses to liver-directed therapy with yttrium 90 microspheres (SIR-Spheres) and adjuvant intraarterial chemotherapy have occurred in patients with unresectable colorectal hepatic metastases who had received less than one chemotherapy regimen. Now, SIR-Spheres are being used to treat patients with advanced disease who have received multiple chemotherapy regimens. A retrospective analysis was performed to determine the technical feasibility of SIR-Sphere treatment in this population. MATERIALS AND METHODS The medical records of 12 patients with hepatic metastatic disease and intrahepatic progression after multiple chemotherapy regimens for unresectable colorectal hepatic metastases who were treated with one or two infusions of SIR-Spheres were retrospectively analyzed for demographics, tumor characteristics, treatment details, response, and survival. RESULTS Twelve patients underwent 17 outpatient infusions of SIR-Spheres. Percent hepatic tumor volume was less than 25% in four patients, 25%-50% in three, and more than 50% in five. Treatment in 11 patients with bilobar disease was accomplished via single infusions in six cases and sequential unilobar infusions in five patients. A single infusion was used to treat unilobar disease in the remaining patient. Median prescribed dose was 39.6 mCi (mean, 37.2 mCi; range, 17-67.5 mCi); the prescribed dose exceeded the delivered dose in six infusions (35%) as a result of embolic arterial occlusion. Radiologic response was stable in five of nine patients. Carcinoembryonic antigen levels decreased in four of seven patients. Four patients received chemotherapy concomitantly or after completion of treatment. Gastric ulceration in one patient was managed nonoperatively. Median survival times from diagnosis and treatment were 24.6 and 4.5 months, respectively. CONCLUSIONS Treatment with SIR-Spheres induces responses in patients with advanced unresectable colorectal hepatic metastases after multiple chemotherapy regimens. Inability to deliver the prescribed dose is related to the embolic effect of SIR-Spheres.

Value of Single Photon Emission Computed Tomography in Acute Stroke Therapeutic Trials

Background and Purpose New therapeutic interventions for acute ischemic stroke are aimed at improving cerebral blood flow in the first 3 to 6 hours after symptom onset. Single-photon emission-computed tomography (SPECT) performed in the setting of clinical therapeutic trials may give us a better understanding of the physiological response to new forms of treatment and could impact acute management decisions. Methods We prospectively studied 15 patients with hemispheric ischemic stroke with SPECT within 6 hours of symptom onset and again at 24 hours. The ischemic defect was assessed in a semiquantitative manner that used computer-generated regions of interest (SPECT graded scale). This measure was correlated with clinical presentation (National Institutes of Health [NIH] Stroke Scale), initial clinical course (change in NIH Stroke Scale), long-term outcome (Barthel Index at 3 months), and complications of cerebral hemorrhage and edema. Results The severity of the SPECT graded scale on the admission scan correlated with the severity of neurological deficit (admission NIH Stroke Scale) (P<.05) and was positively associated with poor long-term outcome as measured with the Barthel Index (P<.001) and the complications of cerebral hemorrhage and massive cerebral edema (P<.005). In fact, there was a threshold value for the SPECT graded scale above which all patients suffered poor long-term outcome and the complications of cerebral hemorrhage and edema. Conclusions The measurement of an ischemic defect using SPECT is a valid assessment of hemispheric stroke severity in the hyperacute setting and may be useful for selecting or stratifying patients in clinical therapeutic trials.

Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

BackgroundIt is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis.MethodsWe performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression.ResultsNo patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does.

Tumor Blood Flow Measured by PET Dynamic Imaging of First-Pass 18F-FDG Uptake: A Comparison with 15O-Labeled Water-Measured Blood Flow

PET molecular imaging of 15O-labeled water is the gold standard for measuring blood flow in humans. However, this requires an on-site cyclotron to produce the short-lived 15O tracer, which is cost-prohibitive for most clinical PET centers. The purpose of this study was to determine if the early uptake of 18F-FDG could be used to measure regional blood flow in tumors in the absence of 15O-water. Methods: PET scans were obtained in patients being evaluated for tumor perfusion and glucose metabolism in a phase I dose-escalating protocol for endostatin, a novel antiangiogenic agent. A 2-min perfusion scan was performed with a bolus injection of 2,220 MBq (60 mCi) of 15O-water, which was followed by a 370-MBq (10 mCi) dose of 18F-FDG. Four sequential scans of 18F-FDG uptake were acquired, consisting of an early 2-min uptake scan—or first-pass scan—and 3 sequential 15-min late 18F-FDG uptake scans. Regions of interest (ROIs) were drawn on 2 or more tumor sites and on back muscle, as a control ROI, for each patient. Arterial blood concentration was derived from the PET scans by drawing an ROI over a large artery in the field of view. Blood flow was computed with a simple 1-compartment blood flow model using the first 2 min of data after injection. Results: Blood flow estimated from the early uptake of 18F-FDG was linearly correlated with 15O-measured blood flow, with an intercept of 0.01, a slope of 0.86, and an R2 regression coefficient of 0.74 (r = 0.86). The 18F-FDG tumor extraction fraction relative to 15O-water averaged 0.86. A preliminary case study of a patient with prostate cancer confirms the utility of the first-pass 18F-FDG blood flow analysis in tumor diagnosis. Conclusion: These results suggest that the first-pass uptake of 18F-FDG may provide an estimate of perfusion in a tumor within the limitations of incomplete extraction of 18F-FDG compared with 15O-water.

Multimodality imaging of aortitis.

Multimodality imaging of aortitis is useful for identification of acute and chronic mural changes due to inflammation, edema, and fibrosis, as well as characterization of structural luminal changes including aneurysm and stenosis or occlusion. Identification of related complications such as dissection, hematoma, ulceration, rupture, and thrombosis is also important. Imaging is often vital for obtaining specific diagnoses (i.e., Takayasu arteritis) or is used adjunctively in atypical cases (i.e., giant cell arteritis). The extent of disease is established at baseline, with associated therapeutic and prognostic implications. Imaging of aortitis may be useful for screening, routine follow up, and evaluation of treatment response in certain clinical settings. Localization of disease activity and structural abnormality is useful for guiding biopsy or surgical revascularization or repair. In this review, we discuss the available imaging modalities for diagnosis and management of the spectrum of aortitis disorders that cardiovascular physicians should be familiar with for facilitating optimal patient care.

Pharmacokinetics, safety, and tolerability of gadoversetamide injection (OptiMARK) in subjects with central nervous system or liver pathology and varying degrees of renal function

The pharmacokinetic parameters, safety, and tolerability of OptiMARK (gadoversetamide injection), a gadolinium‐based magnetic resonance imaging (MRI) contrast agent, were evaluated in 163 subjects with either central nervous system (CNS) or liver pathology with and without renal insufficiency, for which a contrast‐enhanced MRI was indicated. A multicenter, double‐blind, randomized, placebo‐controlled, parallel‐group design was used in which subjects received 0.1, 0.3, or 0.5 mmol/kg of OptiMARK or placebo intravenously. Samples were analyzed for total gadolinium by inductively coupled plasma/mass spectrometry. Gadolinium pharmacokinetics were affected by renal impairment: area under the curve, half‐life, and steady‐state distribution volume significantly increased with declining renal function, while total body clearance decreased. In subjects with normal renal function, neither age, gender, nor liver versus CNS pathology altered gadolinium pharmacokinetics. No clinically significant changes from baseline were noted in vital signs, laboratory measures, electrocardiograms, or physical examinations. OptiMARK is safe and well‐tolerated following a single intravenous injection in subjects with either liver or CNS pathology despite a prolonged elimination half‐life in subjects with renal impairment. J. Magn. Reson. Imaging 1999; 9:317–321.

Demonstration of dose-dependent global and regional cocaine-induced reductions in brain blood flow using a novel approach to quantitative single photon emission computerized tomography

Ischemic stroke is a common cause of morbidity and mortality in cocaine addicts. Because the previous semiquantitative single photon emission computerized tomography (SPECT) method for measuring brain blood flow does not quantify blood flow, the magnitude and specificity of cocaines effects during drug taking has not been well established. Here, using a novel quantitative approach to SPECT, we established that intravenous cocaine administration to nine recently abstinent cocaine-dependent subjects was associated with significant decreases in global and regional brain blood flow to dopamine-rich areas such as the prefrontal, frontal, temporal, and subcortical gray matter. Establishing the utility of this relatively new quantitative SPECT technique provides an important tool for the management of vascular disorders of the brain. Additionally, identifying the site-specific effects of cocaine provides targets for the development of putative therapeutic medications to attenuate or minimize ischemic stroke in cocaine addicts.

Demonstration of hypoperfusion surrounding intracerebral hematoma in humans

We undertook this study to determine whether ischemic regions are present that may contribute to poor outcome after intracerebral hemorrhage (ICH) in humans. Hypoperfusion around an ICH has not been reported in humans. Brain computed tomography (CT) and (99m)Tc-HMPAO brain single photon emission computed tomography (SPECT) perfusion studies were carried out 51 +/- 12 hours after supratentorial ICH in seven patients selected from a referral hospital over an 8-month period. The widest diameters of the hematoma on CT and of reduced perfusion on SPECT were measured and compared. The diameters of reduced perfusion were measured at the 40% and 20% reduced count levels compared with the contralateral side. Reduced perfusion in and around the hematoma was seen in all seven cases. The diameters of ICH on CT (mean, 53 +/- 12 mm) were comparable to the diameters of 40% reduction of counts (mean, 61 +/- 14 mm) measured by SPECT. The mean diameter of brain demonstrating 20% reduction in counts was 76+/-19 mm, which was 43% greater than the hematoma diameter on CT (p = .004). In conclusion, substantial regions of reduced perfusion surround ICH in humans, which might contribute to poor outcome and be amenable to anti-ischemic therapy.

99mTc Anti-CD 15 Monoclonal Antibody (LeuTech) Imaging Improves Diagnostic Accuracy and Clinical Management in Patients With Equivocal Presentation of Appendicitis

BackgroundAppendicitis frequently presents in an atypical fashion leading to misdiagnosis or a delay in diagnosis. This is particularly true in early cases where the patient may be erroneously discharged from an emergency department and will invariably return with perforated appendicitis. The standard of care is hospital admission for observation or early operation. Adjunctive imaging tests have been used with mixed results in this equivocal patient population. The authors studied a promising new monoclonal antibody, 99mTc-labeled anti-CD 15 (LeuTech; Palatin Technologies, Inc., Princeton, NJ), which specifically targets neutrophils and may be used for imaging appendicitis. This prospective, multicenter, open-label study evaluated the diagnostic efficacy and clinical impact of LeuTech scintigraphy for detecting appendicitis in patients with an equivocal presentation. MethodsA total of 200 patients (121 females, 79 males; age range 5–86 years; mean age 30.5 ± 16.5 years) completed the study. Management plan was formulated before and reassessed following LeuTech imaging to determine impact on management. Following intravenous injection of LeuTech, the abdomen was imaged with a standard gamma camera for 30 to 90 minutes. ResultsFifty-nine patients had a histopathologic diagnosis of acute appendicitis. LeuTech identified 53 of 59 patients with appendicitis (90% sensitivity) and was negative in 122 of 141 patients without appendicitis (87% specificity). Accuracy, positive predictive value, and negative predictive value were 88%, 74%, and 95%, respectively. Diagnostic efficacy was unchanged in a subgroup of 48 pediatric patients (5–17 years). Diagnostic images for appendicitis were achieved within 8 minutes postinjection in 50% of patients and within 47 minutes in 90% of patients. Significant shifts in patient management decisions were evident following LeuTech results. LeuTech was well tolerated with no serious adverse events reported. ConclusionLeuTech is a convenient, safe, rapid, and sensitive imaging test for diagnosis of appendicitis and favorably impacts patient management in adult and pediatric patients with equivocal signs and symptoms.

Isradipine prevents global and regional cocaine-induced changes in brain blood flow: A preliminary study

Abstract The L-type calcium channel antagonist, isradipine, reduces brain ischemia in animal models of ischemic stroke. These effects of isradipine appear more pronounced in dopamine (DA) rich brain regions. These same DA-rich brain regions have also been shown to be the areas most affected by cocaine-induced ischemic changes. Using a novel quantified approach to single photon emission computerized tomography, we demonstrated that isradipine pre-treatment prevented cocaine-induced ischemic changes, especially in these DA-rich brain regions. This is the first demonstration that any medication, including isradipine, can prevent the ischemic effects of cocaine on brain blood flow. Isradipine may, therefore, be a useful therapeutic agent for the prevention of brain ischemia in cocaine addicts.