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Notes: Abstract: The 24-h patterns of tissue thyroid hormone concentrations and type II 5′- and type III 5-iodothyronine deiodinase (5′D-II and 5D-III, respectively) activities were determined at 4-h intervals in different brain regions of male euthyroid rats entrained to a regular 12-h light/12-h dark cycle (lights on at 6:00 a.m.). Activity of 5′D-II, which catalyzes the intracellular conversion of thyroxine (T4) to 3,3′,5-triiodo-l-thyronine (T3) in the CNS, and the tissue concentrations of both T4 and T3 exhibited significant daily variations in all brain regions examined. Periodic regression analysis revealed significant circadian rhythms with amplitudes ranging from 9 to 23% (for T3) and from 15 to 40% (for T4 and 5′D-II) of the daily mean value. 5′D-II activity showed a marked nocturnal increase (1.3–2.1-fold vs. daytime basal value), with a maximum at the end of the dark period and a minimum between noon and 4:00 p.m. 5D-III did not exhibit circadian patterns of variation in any of the brain tissues investigated. Our results disclose circadian rhythms of 5′D-II activity and thyroid hormone concentrations in discrete brain regions of rats entrained to a regular 12:12-h light-dark cycle and reveal that, in the rat CNS, T3 biosynthesis is activated during the dark phase of the photoperiod. For all parameters under investigation, the patterns of variation observed were in part regionally specific, indicating that different regulatory mechanisms may be involved in generating the observed rhythms.

Notes: [Auszug] We report here the in vivo diagnostic use of a peptide–dye conjugate consisting of a cyanine dye and the somatostatin analog octreotate as a contrast agent for optical tumor imaging. When used in whole-body in vivo imaging of mouse xenografts, indotricarbocyanine-octreotate accumulated in ...

Notes: Abstract. Human adenocarcinomas of the gastroenteropancreatic system overexpress vasoactive intestinal peptide (VIP) receptors and therefore represent logical diagnostic targets for receptor scintigraphy. Using iodine-123 labelled VIP, the newly employed diagnostic procedure termed VIP receptor scintigraphy (VIP-RS) appears to detect tumour tissue, especially pancreatic metastatic tumours, in almost all cases. So far, however, only a single centre has demonstrated convincing positive results. The aim of this study was to compare the sensitivity and specificity of VIP-RS with those of computer tomography (CT) and transabdominal ultrasound in patients with extensive pancreatic metastatic adenocarcinomas and neuroendocrine tumours. VIP was radiolabelled with carrier-free 123I using the chloramine T-method and preparative high-performance liquid chromatography for purification. Patients with metastatic pancreatic (n=12) and colorectal (n=3) carcinomas (adenocarcinoma: n=13, neuroendocrine tumour: n=2) were studied by VIP-RS, CT, ultrasound and, in one case, also by radioligand receptor autoradiography. Carrier-free radioiodinated VIP of maximum specific radioactivity maintained a high biological activity as determined by cAMP formation in receptor-expressing tumour cell lines. Intravenous injection of 123I-VIP did not cause any side-effects. Biodistribution, determined over 24 h, was high in the lungs and low in abdominal organs. Although all patients had extensive metastatic disease as evidenced by CT and ultrasound, VIP-RS was unable to detect either primaries or metastases in these patients. Only in two patients could a significant uptake of radiolabel be detected in organs directly infiltrated by the primary. To exclude false-negative findings, tumour tissue in one patient with a large primary, undetectable by VIP-RS, was analysed by radioligand receptor autoradiography and shown to be receptor positive. Moreover, in vitro receptor determinations showed that pancreatic carcinomas usually have fewer VIP receptors than the normal tissues to which they metastasize, like the liver. It is concluded that VIP can be radioactively labelled with maximum specific radioactivity while maintaining biological activity. Intravenous administration leads to a biodistribution almost identical to that reported previously. However, in contrast to these reports, very low sensitivity and specificity were observed for the detection of pancreatic cancers. In retrospect, these findings are not surprising since VIP receptor expression was observed to be higher in normal tissues than in neoplastic ones.