THERANOSTICS: From Molecular Imaging Using Ga-68 Labeled Tracers and PET/CT to Personalized Radionuclide Therapy - The Bad Berka Experience

The acronym THERANOSTICS epitomizes the inseparability of diagnosis and therapy, the pillars of medicine and takes into account personalized management of disease for a specific patient. Molecular phenotypes of neoplasms can be determined by molecular imaging with specific probes using positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), or optical methods, so that the treatment is specifically targeted against the tumor and its environment. To meet these demands, we need to define the targets, ligands, coupling and labeling chemistry, the most appropriate radionuclides, biodistribution modifiers, and finally select the right patients for the personalized treatment. THERANOSTICS of neuroendocrine tumors (NETs) using Ga-68 labeled tracers for diagnostics with positron emission tomography/ computed tomography (PET/CT), and using Lu-177 or other metallic radionuclides for radionuclide therapy by applying the same peptide proves that personalized radionuclide therapy today is already a fact and not a fiction

FEM/SINDA: Combining the strengths of NASTRAN, SINDA, I-DEAS, and PATRAN for thermal and structural analysis

This paper describes the interface/integration between FEM/SINDA, a general purpose geometry driven thermal analysis code, and the FEM software: I-DEAS, PATRAN, and NASTRAN. FEM/SINDA brings together the advantages of the finite element method to model arbitrary geometry and anisotropic materials and SINDA's finite difference capability to model thermal properties, loads, and boundary conditions that vary with time or temperature. I-DEAS and PATRAN thermal entities are directly supported since FEM/SINDA uses the nodes of the FEM model as the point at which the temperature is determined. Output from FEM/SINDA (as well as the FEM/SINDA input deck) can be used directly by NASTRAN for structural analysis

188 Rhenium, the New Workhorse of Radio Nuclide Therapy: Concepts to Clinical Use

Editoria

Immunoscintigraphy

Imunoscintigrafija je nova metoda u nuklearnoj medicini, a sastoji se u primjeni monoklonskih protutijela obilježenih 131J, luIn ili 99mTc. Protutijala su specifična za antigene malignih tumora ili za tkivne bjelančevine nastale u zloćudno promijenjenim stanicama za vrijeme patoloških procesa (na primjer: antimyosin). Za rutinske svrhe koristi se 99mTc. Imunoscintigrafija zauzima sve značajnije mjesto u onkologiji za dokazivanje tumorskih recidiva ili za dijagnozu srčanog infarkta.Immunoscintigraphy is a new imaginig technique in nuclear medicine, based on monoclonal antibodies to various antigens labelled by 1311, 11\u27In or 99mTc. The antibodies may be directed against epitopes of malignant tumors (surface antigens) or tissue proteins expressed by a tissue only under pathological conditions (i. e. antimyosin). In routine immunoscintigraphy, "mTc will be the radionucleid of choice. Immunoscintigraphy seems to be of great importance in oncology for imaging tumor relapse and for diagnosing heart infarction

HST [Hubble Space Telescope]/STIS [Space Telescope Imaging Spectrograph] Low Dispersion Spectroscopy of Three Compact Steep Spectrum Sources: Evidence for Jet-Cloud Interaction

We present Hubble Space Telescope Imaging Spectrograph long-slit spectroscopy of the emission line nebulae in the compact steep spectrum radio sources 3C 67, 3C 277.1, and 3C 303.1. We derive BPT (Baldwin- Philips-Terlevich; Baldwin et al. 1981) diagnostic emission line ratios for the nebulae which are consistent with a mix of shock excitation and photoionization in the extended gas. In addition, line ratios indicative of lower ionization gas are found to be associated with higher gas velocities. The results are consistent with a picture in which these galaxy scale radio sources interact with dense clouds in the interstellar medium of the host galaxies, shocking the clouds thereby ionizing and accelerating them

Ramond-Ramond Fields, Fractional Branes and Orbifold Differential K-Theory

We study D-branes and Ramond-Ramond fields on global orbifolds of Type II string theory with vanishing H-flux using methods of equivariant K-theory and K-homology. We illustrate how Bredon equivariant cohomology naturally realizes stringy orbifold cohomology. We emphasize its role as the correct cohomological tool which captures known features of the low-energy effective field theory, and which provides new consistency conditions for fractional D-branes and Ramond-Ramond fields on orbifolds. We use an equivariant Chern character from equivariant K-theory to Bredon cohomology to define new Ramond-Ramond couplings of D-branes which generalize previous examples. We propose a definition for groups of differential characters associated to equivariant K-theory. We derive a Dirac quantization rule for Ramond-Ramond fluxes, and study flat Ramond-Ramond potentials on orbifolds.Comment: 46 pages; v2: typos correcte

Limb interventions in patients undergoing treatment with an unsupported bifurcated aortic endograft system: A review of the Phase II EVT Trial

AbstractIntroduction: Both supported and unsupported bifurcated endograft limbs develop flow-restricting lesions, including kinks, stenoses, and occlusions, which can be identified during or after surgery. Recognition and intervention are essential to achieve long-term graft patency and a satisfactory functional result. This report represents a comprehensive retrospective review of graft limb interventions from the Phase II EVT Trial with the Endovascular Grafting System unsupported bifurcated endograft (Guidant/EVT, Menlo Park, Calif). Methods: The study population consists of 242 patients who underwent treatment with bifurcated endografts implanted during the EVT Phase II Trial. Graft limb interventions have been divided into two groups: those in whom the intervention occurred during surgery versus those in whom the intervention occurred after surgery. Parameters studied included type, incidence, and timing of graft limb intervention, indications for intervention, procedures performed, and overall patient outcome. Results: The mean follow-up period was 31 months. Primary, primary assisted, and secondary limb patency rates were 61.6%, 93.7%, and 97.1%, respectively. Technical success rate at case completion was 97.5%. In 68 of the 242 cases, limb interventions were performed during surgery to assure patency (28.1%). In 28 cases, interventions were performed after surgery (11.6%). Of these postoperative limb problems, 82% occurred during the first 6 months. Repeat limb interventions were necessitated in three patients (1.2%). Within the intraoperative intervention group, perceived indications included kinks (15%), stenosis (57%), dissection (6%), graft redundancy (12%), and instances of twists, thrombosis, and pressure gradients (10%). These findings were successfully managed with percutaneous transluminal angioplasty only (41%), percutaneous transluminal angioplasty and stent (50%), and various combined interventions. Within the postoperative intervention group, symptomatic indications included stenosis (46%) and thrombosis/occlusion (54%). These postoperative limb events were successfully managed with stent (64%), thrombolysis (32%), and femoral-femoral bypass (21%). When limb dysfunction developed in the postoperative setting, it most often occurred within the first 6 months of implantation. Only one patient in this Phase II cohort had a lower extremity amputation unrelated to a graft limb abnormality. Conclusion: The unsupported bifurcated limbs of this endograft necessitated primary adjunctive intervention in 40% of cases. Primary intervention was two times more likely to be performed at the time of the implant rather than after surgery. Repeat limb interventions were not common. Endograft limb flow problems were successfully treated with standard endovascular or surgical interventions or both. These data may support prophylactic stenting of unsupported Ancure graft limbs. A strategy that includes both intraoperative and early postoperative graft limb surveillance is essential to detect reduced limb flow. (J Vasc Surg 2002;36:118-26.

imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real- time monitoring of disease progress and therapeutic efficacy

Geometric K-Homology of Flat D-Branes

We use the Baum-Douglas construction of K-homology to explicitly describe various aspects of D-branes in Type II superstring theory in the absence of background supergravity form fields. We rigorously derive various stability criteria for states of D-branes and show how standard bound state constructions are naturally realized directly in terms of topological K-cycles. We formulate the mechanism of flux stabilization in terms of the K-homology of non-trivial fibre bundles. Along the way we derive a number of new mathematical results in topological K-homology of independent interest.Comment: 45 pages; v2: References added; v3: Some substantial revision and corrections, main results unchanged but presentation improved, references added; to be published in Communications in Mathematical Physic

Gender-related differences in infrarenal aortic aneurysm morphologic features: Issues relevant to Ancure and Talent endografts

AbstractPurpose: The purpose of this study was to determine whether gender-related anatomic variables may reduce applicability of aortic endografting in women. Methods: Data on all patients evaluated at our institution for endovascular repair of their abdominal aortic aneurysm were collected prospectively. Ancure (Endovascular Technologies (EVT)/Guidant Corporation, Menlo Park, Calif) and Talent (World Medical/Medtronic Corporation, Sunrise, Fla) endografts were used. Preoperative imaging included contrast-enhanced computed tomography and arteriography or magnetic resonance angiography. Results: One hundred forty-one patients were evaluated (April 1998–December 1999), 19 women (13.5%) and 122 men (86.5%). Unsuitable anatomy resulted in rejection of 63.2% of the women versus only 33.6% of the men (P = .026). Maximum aneurysm diameter in women and men were similar (women, 56.94 ± 8.23 mm; men, 59.29 ± 13.22 mm; P = .5). The incidence of iliac artery tortuosity was similar across gender (women, 36.8%; men, 54.9%; P = .2). The narrowest diameter of the larger external iliac artery in women was significantly smaller (7.29 ± 2.37 mm) than in men (8.62 ± 2.07 mm; P = .02). The proximal neck length was significantly shorter in women (10.79 ± 12.5 mm) than in men (20.47 ± 19.5 mm; P = .02). The proximal neck width was significantly wider in women (30.5 ± 2.4 mm) than in men (27.5 ± 2.5 mm; P = .013). Proximal neck angulation (>60 degrees) was seen in a significantly higher proportion of women (21%) than men (3.3%; P = .012). Of the patients accepted for endografting, a significantly higher proportion of women required an iliofemoral conduit for access (women, 28.6%; men, 1.2%; P = .016). Conclusion: Gender-related differences in infrarenal aortic aneurysm morphologic features may preclude widespread applicability of aortic endografting in women, as seen by our experience with the Ancure and Talent devices. In addition to a significantly reduced iliac artery size, women are more likely to have a shorter, more dilated, more angulated proximal aortic neck. (J Vasc Surg 2001;33:S77-84.