We compared internalization of three radioiodinated octreotide (OCT) somatostatin (SS) analogs-[125I-Tyr3]OCT, [DTPA degrees, 125I-Tyr3]OCT, and [DOTA degrees,125I-Tyr3]OCT-by somatostatin receptor (SSR)-positive mouse AtT20 pituitary tumor cells and human insulinoma cells. The three SS analogs were internalized in a specific, time-dependent manner. Internalization was significantly inhibited by pertussis toxin (100 microg/l) by 38%, 43%, and 31%, and by an inhibitor of receptor-mediated endocytosis (phenyl arsine oxide; 10 microM) by 98%, 94%, and 92%, respectively. Binding affinities of the three radioligands were comparable (0.2, 0.2, and 0.3 nM, respectively). However, [DOTA degrees,125I-Tyr3]OCT was internalized in a five-fold higher amount in comparison with the two other radioligands. A comparably high uptake of [DOTA degrees, 125I-Tyr3]OCT was found in SSR-positive organs (pituitary, pancreas, and adrenals) in vivo in rats (a ten-fold, five-fold, and eight-fold higher uptake 4 hr post injection, respectively, compared with the two other radioligands). This resulted in very high target-background ratios for [DOTA degrees,125I-Tyr3]OCT 4 hr post injection amounting to 274, 566, and 623 in the pituitary, adrenals, and pancreas, respectively. Both in vivo and in vitro there was a rapid dissociation of radioactivity from the SSR-positive cells. Main conclusions are that: 1) coupling of chelating groups like DTPA or DOTA to the SS analog [Tyr3]OCT does not prevent the internalization of OCT after binding to SSRs; 2) [DOTA degrees, 125I-Tyr3]OCT is internalized in a significantly higher amount by AtT20 and human insulinoma cells and in vivo in rats in SSR-positive organs, in comparison with [DTPA degrees,125I-Tyr3]OCT and [125I-Tyr3]OCT; and 3) the very high target-background ratios in vivo make radioiodinated [DOTA degrees,Tyr3]OCT a very suitable ligand for SSR-targeted radioguided surgery of SSR-positive human neuroendocrine tumors.

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On-line electrical impedance measurement for monitoring blood viscosity during on-pump heart surgery.

BACKGROUND: The viscosity of blood (eta) as well as its electrical impedance at 20 kHz at high shear rate depends on hematocrit, temperature, concentration of macromolecules and red cell deformability. The aim of our study was to investigate the relation between viscosity and electrical impedance in a heart-lung machine-like set-up, because during on-pump heart surgery considerable viscosity changes occur. METHODS: Blood of 10 healthy volunteers was examined under temperature variation between 18.5 and 37 degrees C at four different levels of hemodilution. Blood viscosity was examined with a golden-standard technique, i.e. a Contraves LS 30 Couette viscometer, and the results were compared with measurements of the electrical resistivity (R) at 20 kHz by a specially designed device in series with the tubing system of a heart-lung machine. All measurements were performed at a shear rate of 87 s(-1). RESULTS: Using stepwise multiparameter regression analysis (SPSS) a highly significant correlation was found (r(2) = 0.882) between viscosity (eta) and resistivity (R). Adding the variables sodium ([Na(+)]) and fibrinogen ([Fibr]) concentration the coefficient of correlation further improved to r(2) = 0.928 and the relation became: eta = -0.6844 + 0.038 R + 0.038 [Na(+)] + 0.514 [Fibr]. All coefficients showed a statistical significance of p < 0. 001. CONCLUSIONS: Electrical impedance measurement is feasible in a heart-lung machine-like set-up and allows accurate continuous on-line estimation of blood viscosity; it may offer an adequate way to record and control viscosity changes during on-pump heart surgery.

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Femoral neuropathy after renal transplantation.

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Tissue distribution and metabolism of radioiodinated DTPA0, D-Tyr1 and Tyr3 derivatives of octreotide in rats.

UNLABELLED: Lesions containing somatostatin receptors (SSR) in rats and in man can be visualized in vivo using radiolabeled octreotide (OCT) analogs. SSR scintigraphy was initially performed with [123I-Tyr3]OCT and later with [111In-DTRA0]OCT. With the latter the residence time of radioactivity (111In) in SSR-positive targets is prolonged, most probably due to the DTPA group. Therefore, we hypothesized that its presence might also affect the metabolism of radioiodinated DTPA-OCT analogs. [D-Tyr1]OCT, [DTPA0, D-Tyr1]OCT, [Tyr3]OCT and [DTPA0,Tyr3]OCT were synthesized, and all 4 showed high and specific binding to the SSR in vitro, with IC50 values in the nanomolar range. The rate of internalization of the 4 radioiodinated OCT analogs by mouse AtT20 pituitary tumors cells was in accordance with the IC50 values. The metabolism and tissue distribution of the 4 radioiodinated analogs were investigated in rats at 4, 24 and 48 hours pi, and the tissue vs blood ratios were calculated. High uptake of all OCT analogs was found in the somatostatin receptor-positive tissues at 4 hours, but only remained high at 24 and 48 hours with [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT. Kidney uptake of [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT was also high. Blood clearance and disappearance from muscle was rapid for all 4 analogs. Urinary excretion of [125I-D-Tyr1]OCT, [DTPA0,125I-D-Tyr1]OCT,[125I-Tyr3]OCT and [DTPA0, 125I-Tyr3]OCT amounted to 63%, 67%, 31% and 80% of injected dose respectively. [DTPA0,125I-D-Tyr1]OCT showed highest tissue to blood ratio and residence time in SSR-positive tissues, such as adrenals (ratio: 31, 79, and 66 at 4, 24 and 48 hours respectively) and pancreas (ratio: 14, 48 and 44 at 4, 24 and 48 hours respectively). CONCLUSION: The position of the Tyr residues and the addition of the DTPA group greatly influence the biodistribution of radioiodinated [Tyr]OCT analogs.

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