Detection and characterization of metastatic cervical adenopathy by MR imaging: comparison of different MR techniques

Thirty-five patients scheduled to undergo a neck dissection for squamous cell carcinoma of the head and neck were evaluated preoperatively by magnetic resonance (MR) imaging. Axial and occasionally sagittal and coronal images were obtained. To define the most reliable technique to detect cervical lymph node metastasis, we compared several MR pulse sequences with and without Gd-DTPA administration to histopathologic findings in the neck dissection specimens. T1-weighted spin echo combined with T2-weighted gradient recalled echo (GE) sequences were found to be more useful than any other combination of pulse sequences in localizing lymph nodes. On T2-weighted GE images, lymph nodes were depicted with intermediate to high signal intensity in contrast to low signal muscular and fatty tissue. Gadolinium DTPA enhanced T1-weighted GE images reliably depict central lymph node necrosis, the most specific criterion for lymph node metastasis.     

89Zr immuno-PET: comprehensive procedures for the production of 89Zr-labeled monoclonal antibodies.

The use of immuno-PET, the combination of PET with monoclonal antibodies (mAbs), is an attractive option to improve tumor detection and mAb quantification. The long-lived positron emitter (89)Zr has ideal physical characteristics for immuno-PET, such as a half-life of 3.27 d, which is compatible with the time needed for intact mAbs to achieve optimal tumor-to-nontumor ratios. Thus far, a major limitation in the use of (89)Zr has been the lack of suitable methods for its stable coupling to mAbs. In this article, practical protocols for reproducible isolation of highly pure (89)Zr and the production of optimal-quality mAb-(89)Zr conjugates are provided. METHODS: (89)Zr was produced by a (p,n) reaction on natural yttrium ((89)Y), isolated with a hydroxamate column, and used for labeling of premodified mAbs. mAbs were premodified with a novel bifunctional derivative of the chelate desferrioxamine B (Df) via a new linker chemistry. To this end, Df was initially succinylated (N-sucDf), temporarily filled with Fe(III), esterified by use of tetrafluorophenol, and then directly coupled to mAbs. Chimeric mAb (cmAb) U36, directed against head and neck cancer, was used for in vitro and in vivo evaluation. The in vitro stability of cmAb U36-N-sucDf-(89)Zr was assessed in human serum, and its in vivo behavior was evaluated by biodistribution and PET imaging studies in tumor-bearing nude mice. A cmAb U36-Df-(89)Zr conjugate containing a previously described succinimide ring-thioether unit in the linker was used as a reference. RESULTS: (89)Zr was produced in large batches (6.5-13.5 GBq) and isolated with improved radionuclidic purity (>99.99%) and high yield (>94%). The Df-premodified mAbs gave (89)Zr-labeling efficiencies of 80% within 30 min, resulting in conjugates with preserved integrity and immunoreactivity. With respect to stability, the novel cmAb U36-N-sucDf-(89)Zr conjugate appeared to be superior to the reference conjugate. In vivo, the novel conjugate demonstrated selective tumor targeting, and on PET images obtained at 24, 48, and 72 h after injection of this conjugate, small tumors in the range of 19-154 mg were readily visualized. CONCLUSION: Methods were developed for improved purification of the long-lived positron emitter (89)Zr. Moreover, a novel bifunctional Df chelate was synthesized for the reproducible coupling of (89)Zr to mAbs. The suitability of such conjugates to detect millimeter-sized tumors in xenograft-bearing nude mice was demonstrated.     

Beta-adrenoceptor stimulant properties of amidoalkylamino-substituted 1-aryl-2-ethanols and 1-(aryloxy)-2-propanols

Parallel series of 2-[(2-amidoethyl)amino]-1-arylethanols and 1-[(2-amidoethyl)amino]-3-(aryloxy)-2-propanols have been prepared, and the compounds were tested as beta-adrenoceptor stimulants on the heart and circulation of the dog. The corresponding 2-(alkylamino)-1-arylethanols and 3-(alkylamino)-2-propanols have been tested for comparison and the structure-activity relationships (SAR) examined. The arylethanols are potent full agonists, showing selectivity for the heart relative to blood vessels, while the (aryloxy)propanols are even more cardioselective and are partial agonists. Within a narrow series of 1-[(amidoethyl)amino]-3-(4-hydroxyphenoxy)-2-propanols, careful examination of the SAR of the amide group showed that great variation in cardioselectivity and degree of agonism may be produce. From this study ICI 118587, N-[20[[2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethyl]-4-morpholinecarboxamide, was selected for its high cardioselectivity and 50% agonist properties. This compound in under clinical evaluation as a cardiac stimulant.     

Electrical resistance of the cochlear partition

The relationship between the calculated value of the effective electrical resistance of the cochlear partition and the distance between the electrode for measuring the EP and the stimulating electrodes has been studied. The calculated value of the effective electical resistance of the cochlear partition declines linearly with increasing distance between these electrodes. The correlation coefficient (r) is −0.806. In calculations of the effective electrical resistance of the cochlear partition, attention must be paid to the distance between the microelectrodes.     

Virus infections and acute renal transplant rejection.

The date of onset of 360 acute renal transplant rejection episodes from 1969 to 1973 have been compared with the prevalence of various common viral infections and infections due to Mycoplasma pnuemoniae. A positive correlation was found for influenza B infections (r=0.43, p less than 0.01) up to 5 months before transplantation and for adenovirus infections (r=0.32, p less than 0.05) at 1 month before kidney grafting.