Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors.

In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, His6-(ZHER2:4)2 (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of 99mTc might improve the availability of the labeled conjugate, and Tc(I)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare 99mTc-labeled His6-(ZHER2:4)2 and to evaluate its targeting properties compared with the targeting properties of 125I-4-iodobenzoate-His6-(ZHER2:4)2 [125I-His6-(ZHER2:4)2]. METHODS: The labeling of His6-(ZHER2:4)2 with 99mTc was performed with an IsoLink kit. The specificity of 99mTc-His6-(ZHER2:4)2 binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of 99mTc-His6-(ZHER2:4)2 and 125I-His6-(ZHER2:4)2 in tumor-bearing BALB/c nu/nu mice were determined. RESULTS: The labeling yield for 99mTc-His6-(ZHER2:4)2 was approximately 60% (50 degrees C), and the radiochemical purity was greater than 97%. The conjugate was stable during storage and under histidine and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%IA/g]) of 2.6 %IA/g for 99mTc-His6-(ZHER2:4)2 and 2.3 %IA/g for 125I-His6-(ZHER2:4)2 at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. CONCLUSION: The use of Tc(I)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-His6-(ZHER2:4)2 conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with 99mTc should be investigated further.     

CT scans and lipohaemarthrosis in hip fractures

Computed tomography was performed on 40 patients with recent hip trauma. Radiographs of 25 showed a fracture of the femoral neck with slight displacement; 24 of these had intra-articular fluid and 20 had a lipohaemarthrosis on the CT scan. In 15 patients, radiographs at the time of admission were normal but suspicion of fracture remained. A fracture was later verified in five patients, four of whom had lipohaemarthrosis on admission. In the remaining 10 patients no fracture could be detected; only one patient had a hip joint effusion but no free fat. Thus all 24 patients with lipohaemarthrosis had an intracapsular fracture of the hip. We suggest CT for patients with hip trauma and negative radiographs. The presence of a lipohaemarthrosis of the hip strongly suggests an intra-articular fracture of either the femoral neck or the acetabulum.     

Food intake and patterns of feeding of Norwegian infants

Norway has formed a policy on infant feeding, expressed as dietary allowances and guidelines concerning food intake. In a longitudinal and prospective study of health and development during infancy, the feeding patterns of 217 Norwegian infants were followed in order to evaluate the policy. The findings indicated that prevailing guidelines were largely followed by the parents. Forty-five per cent still got breastmilk at 6 months. Solid foods were usually introduced around 4-5 months, iron-enriched porridge being commonly used. At 10 months 91 per cent were given bread. The nutrient intakes at 10 months were mainly in accordance with the recommendations. The quality of the diet seemed to diminish somewhat when sandwiches replaced porridge. More emphasis should be put upon toddlers' diet in counselling the parents.     

A porcine model for sequential assessments of cerebral haemodynamics and metabolism

We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia.     

Tears of the medial meniscus associated with increased radionuclide activity of the proximal tibia

Summary Three patients who presented with long-standing medial knee pain and normal radiographs had an isotope bone scan in an attempt to arrive at a diagnosis. In each case there was a well-defined area of increased uptake over the medial tibial condyle and arthroscopy subsequently revealed meniscal damage. After arthroscopic menisectomy each patient became asymptomatic and the bone scan returned to normal. We suggest that patients with incapacitating knee pain, normal radiographs and a positive bone scan undergo an arthroscopy even in the absence of clinical signs of meniscal damage.

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Résumé Trois malades qui présentaient depuis longtemps des douleurs de la partie interne du genou et dont les radiographies étaient normales ont bénéficié d'une scintigraphie afin d'essayer d'ðablir un diagnostic. Dans tous les cas il y avait une zone bien limitée d'hyperfixation au niveau de la partie interne de l'extrémité supérieure du tibia, et l'arthroscopie ultérieure découvrit une lésion méniscale. Après méniscectomie arthroscopique tous les malades furent soulagés et la scintigraphie redevint normale. Nous proposons que l'on pratique une arthroscopie, même en l'absence de signes cliniques d'atteinte méniscale, chez les sujets présentant des douleurs notables du genou, avec des radiographies normales et une scintigraphie positive.

     

Cytogenetic studies on human myeloma cell lines

Cell lines (U-266, U-1957, U-1996 and U-2030) established from 4 patients with multiple myeloma (MM) were analyzed cytogenetically. The cell lines represent different stages in B-cell differentiation as evidenced by ultrastructural and functional characteristics. The karyotypic pattern in 3 newly established myeloma lines was studied after a few months in culture and compared to the old myeloma cell line U-266, which was examined after 6, 7 and 8 years of continuous cultivation. Frequency of progressive numerical and structural aberrations during long-term cultivation and their correlation with alterations in growth properties were addressed. We describe the presence of a high frequency of both numerical and structural chromosomal abnormalities in the cells of all 4 myeloma lines studied. Chromosomes often associated with structural abnormalities were 1, 3, 6, 12 and 14. A 14q + marker chromosome was detected in 2 of the 4 cell lines. The breakpoints on the chromosomes participating in structural aberrations in myeloma exhibit some correlation to chromosome sites at or close to locations of mapped oncogenes. No translocations of c-myc were found. These data were further supported by Southern blot analysis (unpublished data). The extent of numerical, but not structural, aberrations correlates with the differentiation stage of the myeloma lines in that the 2 mature lines U-266 and U-1957 were both near-diploid. Multiple progressive chromosomal changes have emerged in U-266 during a period of 8 years with development of independence of feeder cells and increased growth rate. However, capacity for production of complete Ig molecules has remained stable.     

Prognostic factors in invasive squamous cell carcinoma of the vulva.

Histological malignancy grading and its correlation to prognosis were retrospectively investigated in 303 cases of squamous cell carcinoma of the vulva. A scoring system based on several variables is suggested. The scores and the individual histological variables were tested along with clinical factors with a view to predicting survival. Various histological variables including mode of invasion, depth of invasion and nuclear polymorphism, as well as the sum of the scores were good predictors of survival. The study revealed a significantly better survival rate in stage III if no metastases were suspected. An age factor was also found showing that cancer of the vulva has a worse prognosis in older women.