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排序方式: 共有394条查询结果,搜索用时 31 毫秒
1.
Hazel B Breitz Richard E Wendt Michael S Stabin Sui Shen William D Erwin Joseph G Rajendran Janet F Eary Lawrence Durack Ebrahim Delpassand William Martin Ruby F Meredith 《Journal of nuclear medicine》2006,47(3):534-542
166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation. 相似文献
2.
Golli M; Van Nhieu JT; Mathieu D; Zafrani ES; Cherqui D; Dhumeaux D; Vasile N; Rahmouni A 《Radiology》1994,190(3):741
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Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate 总被引:5,自引:2,他引:3
We observed that pretreatment of male F344 rats with benzyl selenocyanate,
a versatile organoselenium chemopreventive agent in several animal model
systems, decreases the levels of DNA and RNA modifications produced in the
liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms
involved, we pretreated male F344 rats with either benzyl selenocyanate,
its sulfur analog benzyl thiocyanate, phenobarbital or cobalt
protoporphyrin IX; the latter is a depletor of P450. We then determined (1)
the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on
2-nitropropane- induced liver DNA and RNA modifications and (3) amount of
nitrate excreted in rat urine following administration of the carcinogen.
Pretreatment with benzyl selenocyanate or phenobarbital increased the
denitrification activity of liver microsomes by 217 and 765%, respectively,
increased liver P4502B1 by 31- and 435-fold, respectively, decreased the
levels of 2-nitropropane-induced modifications in liver DNA (29-70% and
17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and
increased the 24-h urinary excretion of nitrate by 157 and 209%,
respectively. Pretreatment with benzyl thiocyanate had no significant
effect on any of these parameters. Pretreatment with cobalt protoporphyrin
IX decreased liver P4502B 1 by 87%, decreased the denitrification activity
of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate
by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic
acid modifications by 17-67%. These results indicate that the metabolic
sequence from 2-nitropropane to the reactive species causing DNA and RNA
modifications does not involve the removal of the nitro group. Moreover,
they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic
acid modifications in part by increasing its detoxication through induction
of denitrification, although it is evident that other mechanisms must also
be involved.
相似文献
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A model of corrective gene transfer in X-linked ichthyosis 总被引:5,自引:0,他引:5
Freiberg RA; Choate KA; Deng H; Alperin ES; Shapiro LJ; Khavari PA 《Human molecular genetics》1997,6(6):927-933
Single gene recessive genetic skin disorders offer attractive prototypes
for the development of therapeutic cutaneous gene delivery. We have
utilized X-linked ichthyosis (XLI), characterized by loss of function of
the steroid sulfatase arylsulfatase C (STS), to develop a model of
corrective gene delivery to human skin in vivo. A new retroviral expression
vector was produced and utilized to effect STS gene transfer to primary
keratinocytes from XLI patients. Transduction was associated with
restoration of full-length STS protein expression as well as steroid
sulfatase enzymatic activity in proportion to the number of proviral
integrations in XLI cells. Transduced and uncorrected XLI keratinocytes,
along with normal controls, were then grafted onto immunodeficient mice to
regenerate full thickness human epidermis. Unmodified XLI keratinocytes
regenerated a hyperkeratotic epidermis lacking STS expression with
defective skin barrier function, effectively recapitulating the human
disease in vivo. Transduced XLI keratinocytes from the same patients,
however, regenerated epidermis histologically indistinguishable from that
formed by keratinocytes from patients with normal skin. Transduced XLI
epidermis demonstrated STS expression in vivo by immunostaining as well as
a normalization of histologic appearance at 5 weeks post-grafting. In
addition, transduced XLI epidermis demonstrated a return of barrier
function parameters to normal. These findings demonstrate corrective gene
delivery in human XLI patient skin tissue at both molecular and functional
levels and provide a model of human cutaneous gene therapy.
相似文献
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A. KIJLSTRA D. W. KNUTSON M. R. DAHA L. A. VAN ES 《Scandinavian journal of immunology》1979,10(5):421-429
The in vivo behaviour of well-defined immune complexes in rats was studied using complexes derived from DNP-conjugated bovine thyroglobulin (DNP-BTG) and purified specific goat anti-DNP IgG. Both clearance and glomerular localization were mainly dependent on the nature of the antigen. Soluble immune complexes formed with DNP17-BTG were cleared faster and showed a more marked localization in the glomerular mesangium than complexes formed with DNP3.4-BTG. A slight increase in the antibody to antigen ratio seemed to facilitate mesangial localization of soluble immune complexes. Insoluble immune complexes showed temporary localization as microemboli in the lumina of glomerular and peritubular capillaries. This study thus shows that not only the size and composition of the complexes but also the nature of the antigen within the complex can influence the clearance and organ localization of circulating immune complexes. 相似文献
10.
Dackiw AP Sussman JJ Fritsche HA Delpassand ES Stanford P Hoff A Gagel RF Evans DB Lee JE 《Archives of surgery (Chicago, Ill. : 1960)》2000,135(5):550-5; discussion 555-7