Detection of somatostatin receptor-positive tumours using the new 99mTc-tricine-HYNIC-D-Phe1-Tyr3-octreotide: first results in patients and comparison with 111In-DTPA-D-Phe1-octreotide

Indium- 111 labelled DTPA-D-Phe1-octreotide (DTPA-OC, OctreoScan) has been introduced into clinical routine for the detection of somatostatin receptor (SSTR)-positive tumours, which are predominantly of neuroendocrine origin. Potential further applications in other SSTR-positive cancers (e.g. small cell lung cancer, breast cancer, melanoma) have been limited mainly by the restricted availability and the high radionuclide costs. Previous attempts to introduce technetium-99m labelled analogues of octreotide have not been very successful in terms of the labelling procedure, in vivo biodistribution and/or tumour detection capabilities. The aim of this study was to assess the performance of the new 99mTc-labelled analogue HYNIC-D-Phe1-Tyr3-octreotide (HYNIC-TOC), using tricine as co-ligand, for the detection of SSTR-positive tumours in patients in comparison with 111In-DTPA-OC. Overall, 13 patients were examined using 99mTc-tricine-HYNIC-TOC. Twelve patients had proven SSTR-positive tumours, while one patient presented with an SSTR-negative tumour. In 9 of the 13 patients both tracers (99mTc-tricine-HYNIC-TOC and 111In-DTPA-OC) were used. Serial whole-body scans, spot views and/or single-photon emission tomography studies were performed. Images were qualitatively and semi-quantitatively (ROI analyses) evaluated. The biodistribution of 99mTc-tricine-HYNIC-TOC in patients showed high physiological uptake in kidneys, moderate uptake in liver and spleen and little uptake in the gut. The tracer showed predominantly renal and negligible hepatobiliary excretion. Known SSTR-positive tumour sites showed rapid and intense tracer accumulation. 99mTc-tricine-HYNIC-TOC demonstrated rapid tissue uptake within the first hour after injection and had basically no significant clearance (<20%) from normal or tumour tissue thereafter. In contrast, 111In-DTPA-OC showed continuous clearance from normal tissues as well as renal and very little hepatobiliary excretion. Nevertheless, the patterns of accumulation of 99mTc-tricine-HYNIC-TOC in tumours and normal organs were comparable to those of 111In-DTPA-OC. A lesion-by-lesion comparison showed comparable tumour detection capabilities in intrahepatic tumour sites and superior capabilities of 99mTc-tricine-HYNIC-TOC in respect of extrahepatic lesions. In conclusion, 99mTc-tricine-HYNIC-TOC shows promise as a tracer for SSTR imaging, given its favourable clinical characteristics (specific and high receptor affinity, good biodistribution, renal excretion, low radiation exposure, high imaging quality, on-demand availability) and cost-effectiveness. 99mTc-tricine-HYNIC-TOC allows earlier diagnosis (10 min-4 h) compared with 111In-DTPA-OC (4-24 h).     

Hat die In-vitro-Maturation eine Zukunft?

Recent increases in knowledge in reproductive medicine have led to the development of a wide range of methods of assisted reproduction (ART) that can be applied in various infertility situations. Ovarian hyperstimulation with gonadotrophins represents a standardized and highly efficient treatment option to induce polyfollicular development for obtaining numerous oocytes in order to guarantee acceptable pregnancy rates. However, this technique is associated with side effects and disadvantages which has motivated a search for new solutions for infertility treatment. The concept of in-vitro maturation (IM) aims at aspirating immature cumulus-enclosed oocytes at the germinal vesicle stage (GV) from small antral follicles in order to support maturation from the GV stage to the fertilizable metaphase 2 stage (M2) in vitro. At present IVM represents a simple and cost-effective technique and preliminary data suggest that IVM appears to be a safe method. As the development time of clinical IVM is relatively short and pregnancy rates are generally lower, this technique still cannot be equally compared to conventional IVF treatment. However, IVM possesses a great developmental potential for the future.     

Pituitary neoplasia induced by expression of human neurotropic polyomavirus, JCV, early genome in transgenic mice

In recent years, there has been mounting evidence pointing to the association of polyomaviruses with a wide range of human cancers. The human neurotropic polyomavirus, JCV, infecting greater than 75% of the human population produces a regulatory protein named T-antigen which is expressed at the early phase of viral lytic infection and plays a critical role in completion of the viral life cycle. Furthermore, this protein has the ability to transform neural cells in vitro and its expression has been detected in several human neural-origin tumors. To further investigate the oncogenic potential of the JCV early protein in vivo, transgenic mice expressing JCV T-antigen under the control of its own promoter were generated. Nearly 50% of the animals developed large, solid masses within the base of the skull by 1 year of age. Evaluation of the location as well as histological and immunohistochemical data suggest that the tumors arise from the pituitary gland. As T-antigen is known to interact with several cell cycle regulators, the neoplasms were analysed for the presence of the tumor suppressor protein, p53. Immunoprecipitation/Western blot analysis demonstrated overexpression of wild-type, but not mutant p53 within tumor tissue. In addition, co-immunoprecipitation established an interaction between p53 and T-antigen and overexpression of p53 downstream target protein, p21/WAF1. This report describes the analysis of inheritable pituitary adenomas induced by expression of the human polyomavirus, JCV T-antigen in transgenic mice where T-antigen disrupts the p53 pathway by binding to and sequestering wild-type p53. This animal model may serve as a useful tool to further evaluate mechanisms of tumorigenesis by JCV T-antigen.     

Measurement of dose distributions using film in therapeutic electron beams

The feasibility of using film dosimetry data as the input data for patient treatment planning was evaluated. The central-axis depth dose and the off-axis ratios obtained from film measurements in a solid phantom were compared with those of ion-chamber measurements in water. Two techniques were used to generate isodose distributions. The first technique used only the film data, i.e., the central-axis depth dose and the off-axis ratios used for the reconstruction were determined from the film optical density (corrected for film nonlinearity). In the second technique, the central-axis depth dose measured by an ion chamber in a water phantom was combined with the off-axis ratios measured using film in the "solid water" phantom. The resulting isodose distributions from both techniques were compared with the ion-chamber measurements in water for 7-, 12-, and 18-MeV electrons, and the second technique showed better agreement with the ion-chamber measurements than did the first technique. The differences were within a clinically acceptable range.     

Wirkung von Caerulein auf die exokrine Pankreasfunktion des Menschen

Zusammenfassung Untersucht wurde die Sekretionsantwort des exokrinen Pankreas des Menschen auf verschiedene Dosen des synthetischen Dekapeptid Caerulein (Takus). 5, 10 und 20 ng/kg Caerulein während einer Infusion von 0,5 CU/kg/h Sekretin (GIH) i.v. injiziert bewirkten eine lineare Steigerung der Enzymabgabe (Amylase, Lipase, Trypsin und Chymotrypsin) sowie der Sekretin-induzierten Wasser-und Bikarbonatsekretion des Pankreas. Die Injektion von 40 ng/kg Caerulein führte zu keiner weiteren Steigerung der ekbolen Funktion. Intravenös injiziert sind 1 Ivy Hunde-Einheit (IDU/kg) sowie 20 und 40 ng/kg Caerulein in ihrer Wirkung auf das exokrine Pankreas equivalent, es fanden sich keine statistischen Unterschiede.     

Guidelines for surgical treatment of hepatoblastoma in the modern era--recommendations from the Childhood Liver Tumour Strategy Group of the International Society of Paediatric Oncology (SIOPEL)

Cisplatin-containing chemotherapy and complete surgical resection are both crucial in the cure of hepatoblastoma. Radical resection can be obtained either conventionally by partial hepatectomy or with orthotopic liver transplant, but the surgical approach to hepatoblastoma differs considerably across the world. Our main aim in this paper is to present the surgical recommendations of the Childhood Liver Tumour Strategy Group of the International Society of Paediatric Oncology (SIOPEL), as well as to stimulate international debate on this issue. We discuss biopsy, verification of resectability, resection principles, indications and potential contraindications for orthotopic liver transplant, as well as thoracic surgery for pulmonary metastases. We suggest that heroic liver resections with a high probability of leaving residual tumour should be avoided whenever possible. In such cases primary orthotopic liver transplant should be considered. Superior survival rates in hepatoblastoma patients who have received a primary transplant after a good response to chemotherapy support the strategy of avoiding partial hepatectomy in cases where radical resection appears difficult and doubtful. We recommend early referral to a transplant surgeon in cases of: (i) multifocal or large solitary PRETEXT IV (PRE Treatment EXTent of disease scoring system) hepatoblastoma involving all four sectors of the liver and (ii) unifocal, centrally located tumours involving main hilar structures or main hepatic veins. Because complete tumour resection is a prerequisite for cure, any strategy leading to an increased resection rate will result in improved survival. We advise the more frequent use of orthotopic liver transplant, as well as the standardisation of techniques for partial liver resection. These guidelines should not be seen as final, but rather as a starting point for further discussion between the various national and international liver tumour study groups.