Targeted therapy in nuclear medicine—current status and future prospects

In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explore

99mTc-labelled Stealth® liposomal doxorubicin (Caelyx®) in glioblastomas and metastatic brain tumours

British Journal of Cancer (2002) 86, 659–660. DOI: 10.1038/sj/bjc/6600093 www.bjcancer.co

Gender differences in health of EU10 and EU15 populations: the double burden of EU10 men

This study compares gender differences in Healthy Life Years (HLY) and unhealthy life years (ULY) between the original (EU15) and new member states (EU10). Based on the number of deaths, population and prevalence of activity limitations from the Statistics of Living and Income Conditions Survey (SILC) survey, we calculated HLY and ULY for the EU10 and EU15 in 2006 with the Sullivan method. We used decomposition analysis to assess the contributions of mortality and disability and age to gender differences in HLY and ULY. HLY at age 15 for women in the EU10 were 3.1 years more than those for men at the same age, whereas HLY did not differ by gender in the EU15. In both populations ULY at age 15 for women exceeded those for men by 5.5 years. Decomposition showed that EU10 women had more HLY because higher disability in women only partially offset (−0.8 years) the effect of lower mortality (+3.9 years). In the EU15 women’s higher disability prevalence almost completely offset women’s lower mortality. The 5.3 fewer ULY in EU10 men than in EU10 women mainly reflected higher male mortality (4.5 years), while the fewer ULY in EU15 men than in EU15 women reflected both higher male mortality (2.9 years) and higher female disability (2.6 years). The absence of a clear gender gap in HLY in the EU15 thus masked important gender differences in mortality and disability. The similar size of the gender gap in ULY in the EU-10 and EU-15 masked the more unfavourable health situation of EU10 men, in particular the much stronger and younger mortality disadvantage in combination with the virtually absent disability advantage below age 65 in men

[89Zr]-immuno-PET prediction of response to rituximab treatment in patients with therapy refractory interstitial pneumonitis: a phase 2 trial

Introduction: Immune-mediated interstitial pneumonitis may be treated with anti-CD20 therapy after failure of conventional therapies. However, clinical response is variable. It was hypothesized that autoreactive CD20-positive cells may play an important role in this variability. This prospective study aims to elucidate if imaging of CD20-positive cells in the lungs allows prediction of the response to anti-CD20 treatment. Methods: Twenty-one patients with immune-mediated interstitial lung disease (ILD) with deteriorated pulmonary function received a dose of 1000 mg rituximab on day 1 and day 14 spiked with a tracer dose of radiolabeled [89Zr]-rituximab. PET/CT was performed on days 3 and 6. Standardized uptake values (SUV) were calculated as a measure for pulmonary CD20 expression. Based on pulmonary function tests (PFT), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO), prior to and 6 months after treatment, patients were classified as responder (stable disease or improvement) or non-responder. Results: Fifteen patients (71%) were classified as responder. Pulmonary [89Zr]-rituximab PET SUVmean was significantly correlated with the change in FVC and DLCO (K = 0.49 and 0.56, respectively) when using target-to-background ratios, but not when using SUVmean alone. [89Zr]-rituximab SUVmean was significantly higher in responders than in non-responders (0.35 SD 0.09 vs. 0.23 SD 0.06; P = 0.02). Conclusion: Rituximab treatment was effective in the majority of patients. As a higher pulmonary uptake of [89Zr]-rituximab correlated with improvement of PFT and treatment outcome, [89Zr]-rituximab PET imaging may serve as a potential predictive biomarker for anti-CD20 therapy. Trial registration: Clinicaltrials.go

Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT

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Influence of supramolecular forces on the linear viscoelasticity of gluten

Stress relaxation behavior of hydrated gluten networks was investigated by means of rheometry combined with μ-computed tomography (μ-CT) imaging. Stress relaxation behavior was followed over a wide temperature range (0–70 °C). Modulation of intermolecular bonds was achieved with urea or ascorbic acid in an effort to elucidate the presiding intermolecular interactions over gluten network relaxation. Master curves of viscoelasticity were constructed, and relaxation spectra were computed revealing three relaxation regimes for all samples. Relaxation commences with a well-defined short-time regime where Rouse-like modes dominate, followed by a power law region displaying continuous relaxation concluding in a terminal zone. In the latter zone, poroelastic relaxation due to water migration in the nanoporous structure of the network also contributes to the stress relief in the material. Hydrogen bonding between adjacent protein chains was identified as the determinant force that influences the relaxation of the networks. Changes in intermolecular interactions also resulted in changes in microstructure of the material that was also linked to the relaxation behavior of the networks

Citizen science flow – an assessment of simple streamflow measurement methods

Wise management of water resources requires data. Nevertheless, the amount of streamflow data being collected globally continues to decline. Generating hydrologic data together with citizen scientists can help fill this growing hydrological data gap. Our aim herein was to (1) perform an initial evaluation of three simple streamflow measurement methods (i.e., float, salt dilution, and Bernoulli run-up), (2) evaluate the same three methods with citizen scientists, and (3) apply the preferred method at more sites with more people. For computing errors, we used midsection measurements from an acoustic Doppler velocimeter as reference flows. First, we (authors) performed 20 evaluation measurements in headwater catchments of the Kathmandu Valley, Nepal. Reference flows ranged from 6.4 to 240&thinsp;L&thinsp;s−1. Absolute errors averaged 23&thinsp;%, 15&thinsp;%, and 37&thinsp;% with average biases of 8&thinsp;%, 6&thinsp;%, and 26&thinsp;% for float, salt dilution, and Bernoulli methods, respectively. Second, we evaluated the same three methods at 15 sites in two watersheds within the Kathmandu Valley with 10 groups of citizen scientists (three to four members each) and one “expert” group (authors). At each site, each group performed three simple methods; experts also performed SonTek FlowTracker midsection reference measurements (ranging from 4.2 to 896&thinsp;L&thinsp;s−1). For float, salt dilution, and Bernoulli methods, absolute errors averaged 41&thinsp;%, 21&thinsp;%, and 43&thinsp;% for experts and 63&thinsp;%, 28&thinsp;%, and 131&thinsp;% for citizen scientists, while biases averaged 41&thinsp;%, 19&thinsp;%, and 40&thinsp;% for experts and 52&thinsp;%, 7&thinsp;%, and 127&thinsp;% for citizen scientists, respectively. Based on these results, we selected salt dilution as the preferred method. Finally, we performed larger-scale pilot testing in week-long pre- and post-monsoon Citizen Science Flow campaigns involving 25 and 37 citizen scientists, respectively. Observed flows (n=131 pre-monsoon; n=133 post-monsoon) were distributed among the 10 headwater catchments of the Kathmandu Valley and ranged from 0.4 to 425&thinsp;L&thinsp;s−1 and from 1.1 to 1804&thinsp;L&thinsp;s−1 in pre- and post-monsoon, respectively. Future work should further evaluate uncertainties of citizen science salt dilution measurements, the feasibility of their application to larger regions, and the information content of additional streamflow data.</p