External beam radiation therapy (EBRT) for patients with malignant pheochromocytoma and non-head and -neck paraganglioma: combination with 131I-MIBG.

In patients with malignant pheochromocytoma and paraganglioma, 131I-MIBG radiotherapy can achieve an objective response rate of 30-50% with the dose limiting toxicity being hematologic. Patients with disseminated disease, who also have a few index bulky or symptomatic lesions, may benefit from the addition of targeted external beam radiotherapy alone or in combination with systemic 131I-MIBG. The records of patients with malignant paraganglioma who were treated with external beam radiotherapy at the University of Pennsylvania from February 1973 to February 2011 were reviewed in an institutional review board approved retrospective study. Of the 17 patients with tumors in the thorax, abdomen, or pelvis, 76% had local control or clinically significant symptomatic relief for at least 1 year or until death. As expected, the predominant toxicity was due to irradiation of tumor-adjacent normal tissues without clinically significant hematologic toxicity. Due to widespread systemic metastases with areas of bulky, symptomatic tumor, 5 of the 17 patients were treated with sequential 131I-MIBG (2 mCi/kg per treatment) and external beam radiotherapy to 9 sites. In these patients, all areas that were irradiated with external beam radiotherapy showed durable objective response despite all patients eventually experiencing out-of-field systemic progression requiring other treatment. Four of these patients remain alive with excellent performance status 16, 18, 23, and 24 months after external beam radiotherapy. External beam radiotherapy can be highly effective in local management of malignant paraganglioma and can be used in conjunction with 131I-MIBG due to nonoverlapping toxicities with excellent control of locally bulky tumors.

Use of Standardized Uptake Value Ratios Decreases Interreader Variability of [18F] Florbetapir PET Brain Scan Interpretation.

BACKGROUND AND PURPOSE: Fluorine-18 florbetapir is a recently developed ß-amyloid plaque positron-emission tomography imaging agent with high sensitivity, specificity, and accuracy in the detection of moderate-to-frequent cerebral cortical ß-amyloid plaque. However, the FDA has expressed concerns about the consistency of interpretation of [(18)F] florbetapir PET brain scans. We hypothesized that incorporating automated cerebral-to-whole-cerebellar standardized uptake value ratios into [(18)F] florbetapir PET brain scan interpretation would reduce this interreader variability. MATERIALS AND METHODS: This randomized, blinded-reader study used previously acquired [(18)F] florbetapir scans from 30 anonymized patients who were enrolled in the Alzheimer's Disease Neuroimaging Initiative 2. In 4 separate, blinded-reading sessions, 5 readers classified 30 cases as positive or negative for significant ß-amyloid deposition either qualitatively alone or qualitatively with additional adjunct software that determined standardized uptake value ratios. A κ coefficient was used to calculate interreader agreement with and without the use of standardized uptake value ratios. RESULTS: There was complete interreader agreement on 20/30 cases of [(18)F] florbetapir PET brain scans by using qualitative interpretation and on 27/30 scans interpreted with the adjunct use of standardized uptake value ratios. The κ coefficient for the studies read with standardized uptake value ratios (0.92) was significantly higher compared with the qualitatively read studies (0.69, P = .006). CONCLUSIONS: Use of standardized uptake value ratios improves interreader agreement in the interpretation of [(18)F] florbetapir images.

Distribution and partial characterization of CREB-like immunoreactivity in the medicinal leech Hirudo.

The presence and distribution of immunoreactivity to the cyclic AMP response element binding protein (CREB) were determined in the central nervous system (CNS) and in peripheral tissues of the medicinal leech Hirudo. Western blots revealed several CREB-immunoreactive (CREB-IR) bands including one whose molecular weight (43-44 kDa) was similar to mammalian CREB. The 43-44 kDa CREB-like protein was detected in nuclear extracts of the ventral nerve cord and was not observed following preincubation of the primary antiserum with the epitope sequence. CREB-like immunoreactivity was detected in extracts from each of six regions of the leech CNS, and in extracts from leech body wall musculature, crop, intestine, jaw musculature, pharynx, and salivary tissues. Whole mounts of leech ganglia revealed specific CREB-IR in a restricted population of neurons distributed throughout the leech CNS. Apparent homologues to a pair of CREB-IR dorsolateral neurons were observed in most ganglia along the ventral nerve cord. Several CREB-IR neurons exhibited segmental specificity. A number of neurons stained with an antiserum to the cyclic AMP response element modulator (CREM). These neurons showed no overlap in location with CREB-IR neurons, and this staining was not eliminated with a preabsorption control. Possible roles for a CREB-like protein in the leech are discussed.