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.     

Long-latency auditory event-related potentials in schizophrenia and in bipolar and unipolar affective disorder.

Long-latency auditory event-related potentials were examined in 96 subjects with schizophrenia, 99 with bipolar affective disorder and 48 with major depressive (unipolar) disorder, and compared with 32 in-patient and 213 normal controls. The latency of the P3 component was significantly greater in the schizophrenic and bipolar subjects compared to other groups. The difference was stable with respect to clinical state at the time of testing and was not due to age differences or the effect of psychotropic medications. The results support the clinical distinction between bipolar and unipolar affective disorders, but also show that P3 change is not specific to schizophrenia and found in bipolar but not unipolar affective disorder.     

The role of arthroscopy in the problem total knee replacement

Fourteen patients were retrospectively reviewed to examine the role of arthroscopy in the diagnosis and treatment of the problem total knee arthroplasty (TKA), and to define parameters for indications, techniques, and results. All patients had undergone a previous TKA, and postoperatively had problems with pain and/or range of motion. Routine evaluation failed to reveal sepsis or aseptic loosening. Arthroscopy was used to evaluate and treat certain specific conditions. The arthroscope was successful in removing loose bodies, correcting patella subluxation with an arthroscopic lateral release, excising a symptomatic pseudomeniscus, and releasing intraarticular adhesions to improve motion and relieve pain. The postoperative knee score improved 73%. Arthroscopy is a valuable tool to evaluate a painful TKA, and can be used to treat certain conditions that would otherwise require an arthrotomy. The rehabilitation time is easier on the patient and much quicker. Arthroscopy of a TKA does not compromise any future procedures. However, it remains a technically demanding procedure whose indications and expectations are still being defined.     

Pseudophakic bullous keratopathy

The number of cataract extractions in Switzerland has tripled since 1981. In 1986, a total of 15,500 cataract operations were performed, 95% of which were accompanied by an intraocular lens implantation. In spite of this tremendous increase pseudophakic bullous keratopathy remains a rare indication for keratoplasties: between 1980 and 1986 only 20 grafts were performed at the authors' clinic for irreversible corneal edema following lens implantation. After implantation of posterior chamber lenses, penetrating keratoplasty for corneal decompensation is performed after a significantly shorter period (one year) than with anterior chamber lenses (three years), or in iris-supported lenses (four years). In Switzerland, the incidence of pseudophakic bullous keratopathy among patients with posterior chamber lenses is around 0.1 to 0.3%. A long-term investigation of the endothelial cell density over a period of seven years in 16 patients with a Binkhorst two-loop lens revealed a quite stable and satisfactory cell density of 1600 cells/mm2.     

Biomonitoring of benzene exposure by trace analyses of phenylguanine

Summary From preliminary experiments it was known that radiolabelled benzene and some of its metabolites during its metabolic activation process produce different in vitro DNA-phenyladducts in mitoplasts [5, 11].As we reported previously [9] at least one of these adducts, N-7-phenylguanine, is excreted in the urine of rats in measurable amounts, probably through an excision-repair mechanism after an inhalation experiment. Now we found, after i.p. application of benzene in the urine of rats, a compound separated by cation-exchange chromatography that behaves like a synthezised N-7-phenylguanine reference substance with respect to its retention index and the UV-absorption. This finding could be confirmed by HPLC-measurements with reversed-phase carrier materials. Silylation and gaschromatographic/mass spectrometric (GC/MS) separation of the fraction, which contains the phenylguanine, revealed that these fractions contain further phenyl adducts. Furthermore we studied the time-dependent excretion of the DNA-base adduct. Surprisingly the excretion dropped to zero on the fourth day and showed a new increase thereafter.     

Pediatric ophthalmology: reasons for examination and disease pictures

A representative sample of 800 patients was taken from 15,000 children treated between 1972 and 1984 in the Department of Pediatric Ophthalmology of Frankfurt University Eye Hospital. Their charts were reviewed to answer two questions: what are the most frequent reasons for ophthalmological examination in children under 15 years old and what are the most frequent diagnoses? Ophthalmological examinations were most frequently scheduled because of strabismus, errors of refraction and trauma or inflammation of the anterior segment, though also in a large number of cases because of general diseases, most often neurologic diseases such as epilepsy or elevated intracerebral pressure. The diseases diagnosed ophthalmologically were classified as congenital or acquired eye diseases and congenital or acquired general diseases with ocular symptoms. The most frequent are indicated in the text. Acquired diseases were more frequent than congenital diseases, though this group proved to be much larger in pediatric patients than in adult patients.     

Hepatobiliary scintigraphy in a patient with bilhemia

A 4-year-old child referred for acute jaundice following percutaneous needle biopsy of the liver underwent hepatobiliary scintigraphy. Although all conventional liver tests suggested preservation of hepatocyte function, the tracer uptake in the liver appeared dramatically reduced at scintigraphy and the blood pool activity did not decrease significantly until the end of the study. Visualization of the bile ducts indicated, however, that the tracer was taken up by the hepatocyte and further excreted into the biliary tree. There was no tracer pooling in the biliary tree although no bowel activity was observed, even on delayed images. The association of persistent blood pool activity, bile duct visualization without tracer pooling, and nonvisualization of the bowel was caused by a continuous recirculation of the tracer from the biliary tree into the bloodstream. The presence of a biliovenous fistula was further proven by percutaneous transhepatic cholangiography performed 24 h later. Since 1975, only 16 cases of bilhemia have been reported. To the best of our knowledge the scintigraphic pattern of this rare but lifethreatening complication has not previously been reported.