Biokinetik Tc99m-markierter RES-Kolloide im Menschen

The pictorial representation of the liver and spleen by scintigraphic methods is based on radioactive labeling of the RES cells of these organs by Tc-99m colloids, which are largely cleared from the blood by the RES cells following intravenous injection. Estimates of the radiation dose resulting from liver scans are based essentially on biokinetic data derived from animal studies. The aim of this research program was to check the biokinetic data by direct, absolute quantification in man. For this purpose appropriate methods of measurement were developped, in conjunction with other groups involved in this multi-center program. Liver and spleen activities were directly measured using a double energy window technique. Activities in other organs were quantified by the geometric mean of anterior and posterior whole-body scans. The measurement procedures were checked and compared using the Alderson phantom. Biokinetic data were obtained for the four most widely-usedcolloids : sulphur colloid, tin colloid, HSA millimicropheres and phytate. For the sulphur colloid three different commercial preparations were compared. The data obtained are based on 13-20 subjects for each type of colloid. All subjects were clinically free from liver disease, infection, and malignancy. The calculated uptake of activity differed significantly from published values, especially in liver and spleen. The liver uptake was between 54% and 75% of the total administered dose (TAD), whereas MIRD Dose Estimate Report Nr. 3 gives a value of 80%. Depending on the colloid type, spleen uptake was up to four times the 5% TAD value given in the MIRD Report. Activity measured in blood, urine, lung and thyroid proved to be far from negligible. For example, blood activity ranged from 2.4% to 16% TAD and urine activity during the first day was as high as 15% TAD. The uptake in red marrow, though not directly measured, was estimated to be 5% to 10% TAD. The radiation doses to liver and spleen calculated from the biokinetic data measured in man differ from the values published in MIRD Report Nr. 3. The mean calculated liver dose ranges from 49 to 76 $\mu$Gy/MBq (181 to 283 mrem/mCi), depending on the type of colloid. Phytate yielded the lowest spleen dose, 29 $\mu$Gy/MBq (107 mrem/mCi). For other colloids the maximum dose was up to 157 $\mu$Gy/MBq (578 mrem/mCi). The total body dose calculated for the HSA millimicrospheres, 3.5 $\mu$Gy/MBq (13 mrem/mCi), differs significantly from the corresponding MIRD value, whereas that calculated for the other colloids nearly equal the MIRD value of 5.1 $\mu$Gy/MBq (19 mrem/mCi). The results of this work suggest that the animal-based biokinetic data of colloid distribution, especially in liver and spleen, may be corrected on the basis of the direct measurements of absolute uptake in man presented here

Pituitary Adenylate Cyclase Activating Polypeptide : An Important Vascular Regulator in Human Skin in Vivo

Pituitary adenylate cyclase-activating peptide (PACAP) is an important neuropeptide and immunomodulator in various tissues. Although this peptide and its receptors (ie, VPAC1R, VPAC2R, and PAC1R) are expressed in human skin, their biological roles are unknown. Therefore, we tested whether PACAP regulates vascular responses in human skin in vivo. When injected intravenously, PACAP induced a significant, concentration-dependent vascular response (ie, flush, erythema, edema) and mediated a significant and concentration-dependent increase in intrarectal body temperature that peaked at 2.7°C. Topical application of PACAP induced marked concentration-dependent edema. Immunohistochemistry revealed a close association of PACAP-immunoreactive nerve fibers with mast cells and dermal blood vessels. VPAC1R was expressed by dermal endothelial cells, CD4+ and CD8+ T cells, mast cells, and keratinocytes, whereas VPAC2R was expressed only in keratinocytes. VPAC1R protein and mRNA were also detected in human dermal microvascular endothelial cells. The PACAP-induced change in cAMP production in these cells demonstrated VPAC1R to be functional. PACAP treatment of organ-cultured human skin strongly increased the number of CD31+ vessel cross-sections. Taken together, these results suggest that PACAP directly induces vascular responses that may be associated with neurogenic inflammation, indicating for the first time that PACAP may be a crucial vascular regulator in human skin in vivo. Antagonists to PACAP function may be beneficial for the treatment of inflammatory skin diseases with a neurogenic component