The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer

Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management.

Registry for the Evaluation of the Prognostik value of a novel integrated imaging approach combining Single Photon Emission Computed Tomography with coronary calcification imaging (REPROSPECT)

AIMS: Although an added diagnostic and prognostic value of the global coronary artery calcification (CAC) score as an adjunct to single-photon emission computed tomography (SPECT)-myocardial perfusion image (MPI) has been repeatedly documented, none of the previous studies took advantage of the anatomic information provided by the unenhanced cardiac CT. Therefore, no co-registration has so far been used to match a myocardial perfusion defect with calcifications in the subtending coronary artery. To evaluate the prognostic value of integrating SPECT-MPI with CAC images were obtained from non-enhanced cardiac computed tomography (CT) for attenuation correction to predict major adverse cardiac events (MACE). METHODS AND RESULTS: Follow-up was obtained in 462 patients undergoing a 1-day stress/rest (99m)Tc-teterofosmin SPECT and non-enhanced cardiac CT for attenuation correction. Survival free of MACE was determined using the Kaplan-Meier method. After integrating MPI and CT findings, patients were divided into three groups (i) MPI defect matched by calcification (CAC ≥ 1) in the subtending coronary artery (ii) unmatched MPI and CT finding (iii) normal finding by MPI and CT. At a mean follow-up of 34.5 ± 13 months, a MACE was observed in 80 patients (33 death, 6 non-fatal myocardial infarction, 9 hospitalizations due to unstable angina, and 32 revascularizations). Survival analysis revealed the most unfavourable outcome (P < 0.001 log-rank test) for patients with a matched finding. CONCLUSION: In the present study, a novel approach using a combined integration of cardiac SPECT-CAC imaging allows for refined risk stratification, as a matched defect emerged as an independent predictor of MACE.

Acute respiratory syndrome after inhalation of waterproofing sprays: a posteriori exposure-response assessment in 102 cases

Waterproofing agents are widely used to protect leather and textiles in both domestic and occupational activities. An outbreak of acute respiratory syndrome following exposure to waterproofing sprays occurred during the winter 2002-2003 in Switzerland. About 180 cases were reported by the Swiss Toxicological Information Centre between October 2002 and March 2003, whereas fewer than 10 cases per year had been recorded previously. The reported cases involved three brands of sprays containing a common waterproofing mixture, that had undergone a formulation change in the months preceding the outbreak. A retrospective analysis was undertaken in collaboration with the Swiss Toxicological Information Centre and the Swiss Registries for Interstitial and Orphan Lung Diseases to clarify the circumstances and possible causes of the observed health effects. Individual exposure data were generated with questionnaires and experimental emission measurements. The collected data was used to conduct numeric simulation for 102 cases of exposure. A classical two-zone model was used to assess the aerosol dispersion in the near- and far-field during spraying. The resulting assessed dose and exposure levels obtained were spread on large scales, of several orders of magnitude. No dose-response relationship was found between exposure indicators and health effects indicators (perceived severity and clinical indicators). Weak relationships were found between unspecific inflammatory response indicators (leukocytes, C-reactive protein) and the maximal exposure concentration. The results obtained disclose a high interindividual response variability and suggest that some indirect mechanism(s) predominates in the respiratory disease occurrence. Furthermore, no threshold could be found to define a safe level of exposure. These findings suggest that the improvement of environmental exposure conditions during spraying alone does not constitute a sufficient measure to prevent future outbreaks of waterproofing spray toxicity. More efficient preventive measures are needed prior to the marketing and distribution of new waterproofing agents.

Laryngeal and hypopharyngeal carcinomas after (chemo)radiotherapy: a diagnostic dilemma

PURPOSE OF REVIEW: During recent years, (chemo)radiotherapy has evolved into a primary treatment modality for both early and advanced laryngeal and hypopharyngeal carcinomas. Head and neck surgeons will be concerned more frequently with patients presenting symptoms and signs suggesting recurrent tumor or complications of (chemo)radiotherapy. RECENT FINDINGS: Analysis of histologic characteristics and tumor spread of recurrent carcinomas on whole-organ slices of salvage laryngectomy specimens showed that recurrent laryngeal carcinomas are often present with multiple tumor foci dispersed in different regions; furthermore, they may develop beneath an intact mucosa. Only a few articles analyze the reliability of laryngoscopy and biopsy in detecting recurrences after (chemo)radiotherapy: the number of false negative biopsies is relatively high. The differentiation between radionecrosis and tumor recurrence is difficult by computed tomography scan and magnetic resonance imaging in many cases. Positron emission tomography-computed tomography and diffusion-weighted magnetic resonance imaging are promising diagnostic modalities to detect or exclude persistent or recurrent disease after (chemo)radiotherapy. SUMMARY: Endoscopy with biopsy, computed tomography scan and conventional magnetic resonance imaging present several deficiencies in diagnosing recurrent disease after (chemo)radiotherapy. New imaging modalities such as positron emission tomography-computed tomography and diffusion-weighted magnetic resonance imaging show promising results, increasing the diagnostic efficacy.

Evaluation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated bombesin-based radioantagonist for the labeling with single-photon emission computed tomography, positron emission tomography, and therapeutic radionuclides

PURPOSE: G protein-coupled receptor agonists are being used as radiolabeled vectors for in vivo localization and therapy of tumors. Recently, somatostatin-based antagonists were shown to be superior to agonists. Here, we compare the new [111In/68Ga]-labeled bombesin-based antagonist RM1 with the agonist [111In]-AMBA for targeting the gastrin-releasing peptide receptor (GRPR). EXPERIMENTAL DESIGN: IC50, Kd values, and antagonist potency were determined using PC-3 and HEK-GRPR cells. Biodistribution and imaging studies were done in nude mice transplanted with the PC-3 tumor. The antagonist potency was assessed by evaluating the effects on calcium release and on receptor internalization monitored by immunofluorescence microscopy. RESULTS: The IC50 value of [(nat)In]-RM1 was 14 +/- 3.4 nmol/L. [(nat/111)In]-RM1 was found to bind to the GRPR with a Kd of 8.5 +/- 2.7 nmol/L compared with a Kd of 0.6 +/- 0.3 nmol/L of [111In]-AMBA. A higher maximum number of binding site value was observed for [111In]-RM1 (2.4 +/- 0.2 nmol/L) compared with [111In]-AMBA (0.7 +/- 0.1 nmol/L). [(nat)Lu]-AMBA is a potent agonist in the immunofluorescence-based internalization assay, whereas [(nat)In]-RM1 is inactive alone but efficiently antagonizes the bombesin effect. These data are confirmed by the calcium release assay. The pharmacokinetics showed a superiority of the radioantagonist with regard to the high tumor uptake (13.4 +/- 0.8% IA/g versus 3.69 +/- 0.75% IA/g at 4 hours after injection. as well as to all tumor-to-normal tissue ratios. CONCLUSION: Despite their relatively low GRPR affinity, the antagonists [111In/68Ga]-RM1 showed superior targeting properties compared with [111In]-AMBA. As found for somatostatin receptor-targeting radiopeptides, GRP-based radioantagonists seem to be superior to radioagonists for in vivo imaging and potentially also for targeted radiotherapy of GRPR-positive tumors.

Neural correlates of free T3 alteration after catecholamine depletion in subjects with remitted major depressive disorder and in controls.

RATIONALE: Thyroid hormones and their interactions with catecholamines play a potentially important role in alterations of mood and cognition. OBJECTIVES: This study aimed to examine the neurobiological effects of catecholamine depletion on thyroid hormones by measuring endocrine and cerebral metabolic function in unmedicated subjects with remitted major depressive disorder (RMDD) and in healthy controls. METHODS: This was a randomized, placebo-controlled, and double-blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy control subjects. The participants underwent two 3-day-long sessions at 1-week intervals; each participant was randomly administered oral α-methyl-para-tyrosine in one session (catecholamine depletion) and an identical capsule containing hydrous lactose (sham depletion) in the other session prior to a [(18)F]-fluorodeoxyglucose positron emission tomography scan. RESULTS: Serum concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and assessed with respect to their relationship to regional cerebral glucose metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less suppressed after catecholamine depletion compared with placebo treatment in the entire study sample. There was a positive association between both FT3 (P = 0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale. The relative elevation in FT3 level was correlated with a decrease in regional glucose metabolism in the right dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected). CONCLUSIONS: This study provided evidence of an association between a thyroid-catecholamine interaction and mood regulation in the rDLPFC.

A Cruciform Electron Donor-Acceptor Semiconductor with Solid-State Red Emission: 1D/2D Optical Waveguides and Highly Sensitive/Selective Detection of H2S Gas

In this paper, a new cruciform donor–acceptor molecule 2,2'-((5,5'-(3,7-dicyano-2,6-bis(dihexylamino)benzo[1,2-b:4,5-b']difuran-4,8-diyl)bis(thiophene-5,2-diyl))bis (methanylylidene))dimalononitrile (BDFTM) is reported. The compound exhibits both remarkable solid-state red emission and p-type semiconducting behavior. The dual functions of BDFTM are ascribed to its unique crystal structure, in which there are no intermolecular face-to-face π–π interactions, but the molecules are associated by intermolecular CN…π and H-bonding interactions. Firstly, BDFTM exhibits aggregation-induced emission; that is, in solution, it is almost non-emissive but becomes significantly fluorescent after aggregation. The emission quantum yield and average lifetime are measured to be 0.16 and 2.02 ns, respectively. Crystalline microrods and microplates of BDFTM show typical optical waveguiding behaviors with a rather low optical loss coefficient. Moreover, microplates of BDFTM can function as planar optical microcavities which can confine the emitted photons by the reflection at the crystal edges. Thin films show an air-stable p-type semiconducting property with a hole mobility up to 0.0015 cm2V−1s−1. Notably, an OFET with a thin film of BDFTM is successfully utilized for highly sensitive and selective detection of H2S gas (down to ppb levels).

Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist - from mice to men

UNLABELLED Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy. METHODS Biodistribution, dosimetry and tumor uptake of the GRPr antagonist ⁶⁴Cu-CB-TE2A-AR06 [(⁶⁴Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG₄-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH₂] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7). RESULTS No adverse events were observed after injection of ⁶⁴Cu-CB-TE2A-AR06. Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time. CONCLUSION ⁶⁴Cu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate cancer. Future studies evaluating ⁶⁴Cu-CB-TE2A-AR06 PET/CT for prostate cancer detection, staging, active surveillance, and radiation treatment planning are necessary.

Final Results of a Prospective Evaluation of the Predictive Value of Interim Positron Emission Tomography in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP-14 (SAKK 38/07)

PURPOSE Our main objective was to prospectively determine the prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after two cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 14 days (R-CHOP-14) under standardized treatment and PET evaluation criteria. PATIENTS AND METHODS Patients with any stage of diffuse large B-cell lymphoma were treated with six cycles of R-CHOP-14 followed by two cycles of rituximab. PET/CT examinations were performed at baseline, after two cycles (and after four cycles if the patient was PET-positive after two cycles), and at the end of treatment. PET/CT examinations were evaluated locally and by central review. The primary end point was event-free survival at 2 years (2-year EFS). RESULTS Median age of the 138 evaluable patients was 58.5 years with a WHO performance status of 0, 1, or 2 in 56%, 36%, or 8% of the patients, respectively. By local assessment, 83 PET/CT scans (60%) were reported as positive and 55 (40%) as negative after two cycles of R-CHOP-14. Two-year EFS was significantly shorter for PET-positive compared with PET-negative patients (48% v 74%; P = .004). Overall survival at 2 years was not significantly different, with 88% for PET-positive versus 91% for PET-negative patients (P = .46). By using central review and the Deauville criteria, 2-year EFS was 41% versus 76% (P < .001) for patients who had interim PET/CT scans after two cycles of R-CHOP-14 and 24% versus 72% (P < .001) for patients who had PET/CT scans at the end of treatment. CONCLUSION Our results confirmed that an interim PET/CT scan has limited prognostic value in patients with diffuse large B-cell lymphoma homogeneously treated with six cycles of R-CHOP-14 in a large prospective trial. At this point, interim PET/CT scanning is not ready for clinical use to guide treatment decisions in individual patients.