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1.
Rolleman EJ Krenning EP Bernard BF de Visser M Bijster M Visser TJ Vermeij M Lindemans J de Jong M 《European journal of nuclear medicine and molecular imaging》2007,34(2):219-227
Purpose and methods Studies on peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues have shown promising results
with regard to tumour control. The efficacy of PRRT is limited by uptake and retention in the proximal tubules of the kidney,
which might lead to radiation nephropathy. We investigated the long-term renal toxicity after different doses of [177Lu-DOTA0,Tyr3]octreotate and the effects of dose fractionation and lysine co-injection in two tumour-bearing rat models.
Results Significant renal toxicity was detected beyond 100 days after start of treatment as shown by elevated serum creatinine and
proteinuria. Microscopically, tubules were strongly dilated with flat epithelium, containing protein cylinders. Creatinine
levels rose significantly after 555 MBq [177Lu-DOTA0,Tyr3]octreotate, but were significantly lower after 278 MBq (single injection) or two weekly doses of 278 MBq. Renal damage scores
were maximal after 555 MBq and significantly lower in the 278 and 2×278 MBq groups. Three doses of 185 MBq [177Lu-DOTA0,Tyr3]octreotate with intervals of a day, a week or a month significantly influenced serum creatinine (469±18, 134±70 and 65±15 μmol/l,
respectively; p<0.001). Renal histological damage scores were not significantly influenced by dose fractionation. Lysine co-administration
with three weekly treatments of 185 MBq significantly lowered serum creatinine and proteinuria.
Conclusion Injection of high doses of [177Lu-DOTA0,Tyr3]octreotate resulted in severe renal damage in rats as indicated by proteinuria, elevated serum creatinine and histological
damage. This damage was dose dependent and became overt between 100 and 200 days after treatment. Dose fractionation had significant
beneficial effects on kidney function. Also, lysine co-injection successfully prevented functional damage. 相似文献
2.
Jaap J. M. Teunissen Eric P. Krenning Frank H. de Jong Yolanda B. de Rijke Richard A. Feelders Maarten O. van Aken Wouter W. de Herder Dik J. Kwekkeboom 《European journal of nuclear medicine and molecular imaging》2009,36(11):1758-1766
Purpose
Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. 相似文献3.
Esser JP Krenning EP Teunissen JJ Kooij PP van Gameren AL Bakker WH Kwekkeboom DJ 《European journal of nuclear medicine and molecular imaging》2006,33(11):1346-1351
Purpose Patients with somatostatin receptor subtype 2-positive metastasised neuroendocrine tumours can be treated with [177Lu-DOTA0,Tyr3]octreotate. Some use octreotide as the peptide for peptide receptor radionuclide therapy (PRRT). We compared in seven patients [177Lu-DOTA0,Tyr3]octreotide (177Lu-DOTATOC) and [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE), to see which peptide should be preferred for PRRT with 177Lu.Methods In the same patients, 3,700 MBq 177Lu-DOTATOC and 3,700 MBq 177Lu-DOTATATE was administered in separate therapy sessions. Amino acids were co-administered. Whole-body scanning was performed on days 1, 4 and 7 post therapy. Blood and urine samples were collected. We calculated residence times for tumours, spleen and kidneys.Results All patients had longer residence times in spleen, kidneys and tumours after use of 177Lu-DOTATATE (p=0.016 in each case). Comparing 177Lu-DOTATATE with 177Lu-DOTATOC, the mean residence time ratio was 2.1 for tumour, 1.5 for spleen and 1.4 for kidneys. Dose-limiting factors for PRRT are bone marrow and/or kidney dose. Although the residence time for kidneys was longer when using 177Lu-DOTATATE, the mean administered dose to tumours would still be advantageous by a factor of 1.5, assuming a fixed maximum kidney dose is reached. Plasma radioactivity after 177Lu-DOTATATE was comparable to that after 177Lu-DOTATOC. Urinary excretion of radioactivity was comparable during the first 6 h; thereafter there was a significant advantage for 177Lu-DOTATOC.Conclusion
177Lu-DOTATATE had a longer tumour residence time than 177Lu-DOTATOC. Despite a longer residence time in kidneys after 177Lu-DOTATATE, tumour dose will always be higher. Therefore, we conclude that the better peptide for PRRT is octreotate. 相似文献
4.
de Keizer B van Aken MO Feelders RA de Herder WW Kam BL van Essen M Krenning EP Kwekkeboom DJ 《European journal of nuclear medicine and molecular imaging》2008,35(4):749-755
Introduction Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative
treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled
somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate).
Materials and methods All 177Lu-octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic
neuroendocrine tumors and three patients with metastatic pheochromocytoma were included for analysis.
Results Four hundred seventy-nine patients received a total of 1,693 administrations of 177Lu-octreotate. Six of 479 patients (1%) developed severe symptoms because of massive release of bioactive substances after
the first cycle of 177Lu-octreotate. One patient had a metastatic hormone-producing small intestinal carcinoid; two patients had metastatic, hormone-producing
bronchial carcinoids; two patients had vasoactive intestinal polypeptide-producing pancreatic endocrine tumors (VIPomas);
and one patient had a metastatic pheochromocytoma. With adequate treatment, all patients eventually recovered.
Conclusion Hormonal crises after 177Lu-octreotate therapy occur in 1% of patients. Generally, 177Lu-octreotate therapy is well tolerated. 相似文献
5.
Hendrik Bergsma Mark W. Konijnenberg Wouter A. van der Zwan Boen L. R. Kam Jaap J. M. Teunissen Peter P. Kooij Katya A. L. Mauff Eric P. Krenning Dik J. Kwekkeboom 《European journal of nuclear medicine and molecular imaging》2016,43(10):1802-1811
Purpose
After peptide receptor radionuclide therapy (PRRT), renal toxicity may occur, particular in PRRT with 90Y-labelled somatostatin analogues. Risk factors have been identified for increased probability of developing renal toxicity after PRRT, including hypertension, diabetes and age. We investigated the renal function over time, the incidence of nephrotoxicity and associated risk factors in patients treated with PRRT with [177Lu-DOTA0,Tyr3]-Octreotate (177Lu-Octreotate). Also, radiation dose to the kidneys was evaluated and compared with the accepted dose limits in external beam radiotherapy and PRRT with 90Y-radiolabelled somatostatin analogues.Methods
The annual decrease in creatinine clearance (CLR) was determined in 209 Dutch patients and the incidence of grade 3 or 4 renal toxicity (according to CTCAE v4.03) was evaluated in 323 patients. Risk factors were analysed using a nonlinear mixed effects regression model. Also, radiation doses to the kidneys were calculated and their association with high annual decrease in renal function were analysed.Results
Of the 323 patients, 3 (1 %) developed (subacute) renal toxicity grade 2 (increase in serum creatinine >1.5?–?3.0 times baseline or upper limit of normal). No subacute grade 3 or 4 nephrotoxicity was observed. The estimated average baseline CLR (±?SD) was 108?±?5 ml/min and the estimated average annual decrease in CLR (±?SD) was 3.4?±?0.4 %. None of the risk factors (hypertension, diabetes, high cumulative injected activity, radiation dose to the kidneys and CTCAE grade) at baseline had a significant effect on renal function over time. The mean absorbed kidney dose in 228 patients was 20.1?±?4.9 Gy.Conclusion
Nephrotoxicity in patients treated with 177Lu-octreotate was low. No (sub)acute grade 3 or 4 renal toxicity occurred and none of the patients had an annual decrease in renal function of >20 %. No risk factors for renal toxicity could be identified. Our data support the idea that the radiation dose threshold, adopted from external beam radiotherapy and PRRT with 90Y-labelled somatostatin analogues, does not seem valid for PRRT with 177Lu-octreotate.6.
Laverman P Roosenburg S Gotthardt M Park J Oyen WJ de Jong M Hellmich MR Rutjes FP van Delft FL Boerman OC 《European journal of nuclear medicine and molecular imaging》2008,35(2):386-392
Purpose Radiolabelled cholecystokinin (CCK) and gastrin-derived peptides potentially can be used for peptide receptor radionuclide
therapy (PRRT). Recently, a splice variant version of the CCK2R has been identified, designated CCK2i4svR. Constitutive expression
of this receptor has been demonstrated in human colorectal cancer and in pancreatic cancer, but not in normal tissue. So far,
it has never been shown whether radiolabelled peptides can target the CCK2i4svR in vivo. In this paper, we investigated the
potential of sulfated 111In-labelled DOTA-CCK8 (sCCK8), a pan-CCKR-binding peptide, and [111In]DOTA-minigastrin (MG0), a CCK2R selective peptide, for the targeting of the CCK2i4svR.
Materials and methods The receptor binding affinity of [111In]DOTA-sCCK8 and [111In]DOTA-MG0 for the CCK2R and CCK2i4svR was determined using stably transfected HEK293 cell lines, expressing either CCK2R
or CCK2i4svR. Tumour targeting was studied in HEK293-CCK2i4svR tumour-bearing athymic mice.
Results [111In]DOTA-sCCK8 as well as [111In]DOTA-MG0 specifically bound both CCK2R and CCK2i4svR with affinities in the low nanomolar range. In vivo experiments revealed
that accumulation of both peptides in CCK2i4svR-positive tumours was similar (3.21 ± 0.77 and 3.01 ± 0.67%ID/g, sCCK8 and
MG0, respectively, 24 h p.i.). Kidney retention of [111In]DOTA-MG0 (32.4 ± 7.5%ID/g, 24 h p.i.) was markedly higher than that of [111In]DOTA-sCCK8 (2.75 ± 0.31%ID/g, 24 h p.i.).
Conclusion We demonstrated that the CCK2i4svR is a potential target for PRRT using a radiolabelled sulfated CCK8 peptide. As this receptor
is expressed on colorectal and pancreatic tumours, but not in normal tissue, these tumours are potentially new targets for
PRRT with CCK8 and gastrin analogs. 相似文献
7.
Flavio Forrer Eric P. Krenning Peter P. Kooij Bert F. Bernard Mark Konijnenberg Willem H. Bakker Jaap J. M. Teunissen Marion de Jong Kirsten van Lom Wouter W. de Herder Dik J. Kwekkeboom 《European journal of nuclear medicine and molecular imaging》2009,36(7):1138-1146
Purpose Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys,
the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according
to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of
the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors.
We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates.
Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called
“remainder of the body” to the bone marrow.
Methods Bone marrow aspirates were drawn in 15 patients after treatment with [177Lu-DOTA0,Tyr3]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated
cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow
was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment.
Results A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the
blood was found (r=0.914, p<0.001). No correlation between the calculated absorbed dose in the bone marrow and the change in platelets was found. There
was a considerable contribution from other organs and the remainder of the body to the bone marrow absorbed dose.
Conclusion (1) After PRRT with [177Lu-DOTA0,Tyr3]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant
binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source
organs and tumours to the bone marrow dose is significant; and (4) There is considerable variation in bone marrow absorbed
dose between patients. These findings imply that for individual dose optimization, individual calculation of the bone marrow
absorbed dose is necessary. 相似文献
8.
M. Pissarek J. Meyer-Kirchrath T. Hohlfeld S. Vollmar A. M. Oros-Peusquens U. Flögel C. Jacoby U. Krügel N. Schramm 《European journal of nuclear medicine and molecular imaging》2009,36(9):1495-1509
Purpose The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of 123I- and 99mTc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose
range thresholds for verification of differences in tracer uptake.
Methods A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of
the dopamine D2 receptor ligand [123I]IBZM and the cerebral perfusion tracer [99mTc]HMPAO (1.2–0.4 MBq/g body weight) in healthy mice. The fatty acid [123I]IPPA (0.94 ± 0.05 MBq/g body weight) and the perfusion tracer [99mTc]sestamibi (3.8 ± 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP3 receptor.
Results In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation
of striatal [123I]IBZM and of cardiac [99mTc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [123I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [99mTc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [123I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight.
Conclusion Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of 123I- and 99mTc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The
thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect
distinctions in molar activity and uptake characteristics of the tracers.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
9.
Bodei L Cremonesi M Ferrari M Pacifici M Grana CM Bartolomei M Baio SM Sansovini M Paganelli G 《European journal of nuclear medicine and molecular imaging》2008,35(10):1928-1856
Purpose Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumours with 90Y-DOTATOC and 177Lu-DOTATATE is promising. The kidney is the critical organ and despite renal protection, function loss may become evident
years later. The aim of this study was to analyse renal parameters in patients who had undergone dosimetry before PRRT.
Methods Among those in protocols at our institution, 28 patients were considered: 23 received 90Y-DOTATOC (3.8–29.2 GBq, median 12.2) and five received 177Lu-DOTATATE (20.7–29.2 GBq, median 23.2). Patients were followed up after therapy for creatinine and creatinine clearance
loss (CCL) for 3–97 months (median 30). Renal doses and bio-effective doses (BED) were calculated (MIRD, LQ model).
Results After 90Y-DOTATOC toxicity on creatinine according to NCI criteria occurred in nine cases (seven grade 1, one grade 2, one grade 3),
CCL at 1 year was >5% in 12 cases and >10% in eight. A 28-Gy BED threshold was observed in patients with risk factors (mainly
hypertension and diabetes), while it was 40 Gy in patients without risk factors. Probably due to the low number of patients,
despite the absence of severe toxicity after hyper-fractionated PRRT, clear correlations between fractionation and toxicity
could not be found. After 177Lu-DOTATATE, no toxicity occurred in 1–2 year follow-up; CCL at 1 year >5% occurred in three patients and >10% in two.
Conclusions Our results indicate the importance of clinical screening for risk factors: In this case, a BED <28 Gy is recommended. Fractionation
of therapy is important in order to decrease toxicity, and further studies are needed to evaluate its clinical impact.
An erratum to this article can be found at 相似文献
10.
Rebecca A. Gregory Claire A. Hooker Mike Partridge Glenn D. Flux 《European journal of nuclear medicine and molecular imaging》2009,36(7):1037-1048
Purpose Quantitative 124I PET imaging is challenging as 124I has a complex decay scheme. In this study the performance of a Philips Gemini dual GS PET/CT system was optimized and assessed
for 124I.
Methods The energy window giving the maximum noise equivalent count rate (NECR) and NEMA 2001-NU2 image quality were measured. The
activity concentration (AC) accuracy of images calibrated using factors from 18F and 124I decaying source measurements were investigated.
Results The energy window 455–588 keV gave the maximum NECR of 9.67 kcps for 233 MBq. 124I and 18F image quality was comparable, although 124I background variability was increased. The average underestimation in AC in 124I images was 17.9 ± 2.9% for nonuniform background and 14.7 ± 2.9% for single scatter simulation (SSS) subtraction scatter
correction. At 224 MBq the underestimation was 10.8 ± 11.3%, which is comparable to 7.7 ± 5.3% for 18F, but increased with decreasing activity.
Conclusions The best 124I PET quantitative accuracy was achieved for the optimized energy window, using SSS scatter correction and calibration factors
from decaying 124I source measurements. The quantitative accuracy for 124I was comparable to that for 18F at high activities of 224 MBq but diminishing with decreasing activity. Specific corrections for prompt γ-photons may further
improve the quantitative accuracy. 相似文献
11.
Takano A Halldin C Varrone A Karlsson P Sjöholm N Stubbs JB Schou M Airaksinen AJ Tauscher J Gulyás B 《European journal of nuclear medicine and molecular imaging》2008,35(3):630-636
Purpose (S,S)-[18F]FMeNER-D2 is a recently developed positron-emission tomography (PET) radioligand for in vivo quantification of the norepinephrine transporter
system. The aim of this study was to provide dosimetry estimates for (S,S)-[18F]FMeNER-D2 based on human whole-body PET measurements.
Methods PET scans were performed for a total of 6.4 h after the injection of 168.9 ± 31.5 MBq of (S,S)-[18F]FMeNER-D2 in four healthy male subjects. Volumes of interest were drawn on the coronal images. Estimates of the absorbed dose of radiation
were calculated using the OLINDA software.
Results Uptake was largest in lungs, followed by liver, bladder, brain and other organs. Peak values of the percent injected dose
(%ID) at a time after radioligand injection were calculated for the lung (21.6%ID at 0.3 h), liver (5.1%ID at 0.3 h), bladder
(12.2%ID at 6 h) and brain (2.3%ID at 0.3 h). The largest absorbed dose was found in the urinary bladder wall (0.039 mGy/MBq).
The calculated effective dose was 0.017 mSv/MBq.
Conclusion Based on the distribution and dose estimates, the estimated radiation burden of (S,S)-[18F]FMeNER-D2 is lower than that of [18F]FDG. The radioligand would allow multiple PET examinations in the same research subject per year. 相似文献
12.
Bernard M. Tijink Lars R. Perk Marianne Budde Marijke Stigter-van Walsum Gerard W. M. Visser Reina W. Kloet Ludger M. Dinkelborg C. René Leemans Dario Neri Guus A. M. S. van Dongen 《European journal of nuclear medicine and molecular imaging》2009,36(8):1235-1244
Purpose The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of
tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with 131I-L19-SIP was recently started. In the present study, after GMP production of 124I and efficient production of 124I-L19-SIP, we aimed to demonstrate the suitability of 124I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical
131I-L19-SIP RIT.
Methods
124I was produced in a GMP compliant way via 124Te(p,n)124I reaction and using a TERIMO™ module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of
the IODO-GEN method. The biodistribution of coinjected 124I- and 131I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while 124I PET images were obtained from mice with tumours of <50 to ∼700 mm3.
Results
124I was produced highly pure with an average yield of 15.4 ± 0.5 MBq/μAh, while separation yield was ∼90% efficient with <0.5%
loss of TeO2. Overall labelling efficiency, radiochemical purity and immunoreactive fraction were for 124I-L19-SIP: ∼80 , 99.9 and >90%, respectively. Tumour uptake was 7.3 ± 2.1, 10.8 ± 1.5, 7.8 ± 1.4, 5.3 ± 0.6 and 3.1 ± 0.4%ID/g
at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i..
Fully concordant labelling and biodistribution results were obtained with 124I- and 131I-L19-SIP. Immuno-PET with 124I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm3 and no adverse uptake in other organs.
Conclusions
124I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with 124I-L19-SIP appeared qualified for sensitive imaging of tumour neovasculature and for predicting 131I-L19-SIP biodistribution.
Bernard M. Tijink and Lars R. Perk contributed equally to this article. 相似文献
13.
Mattias Sandström Ulrike Garske Dan Granberg Anders Sundin Hans Lundqvist 《European journal of nuclear medicine and molecular imaging》2010,37(2):212-225
Purpose
In recent years, targeted radionuclide therapy with [177Lu-DOTA0, Tyr3]octreotate for neuroendocrine tumours has yielded promising results. This therapy may be further improved by using individualized dosimetry allowing optimization of the absorbed dose to the tumours and the normal organs. The aim of this study was to investigate the feasibility and reliability of individualized dosimetry based on SPECT in comparison to conventional planar imaging.Methods
Attenuation-corrected SPECT data were analysed both by using organ-based volumes of interest (VOIs) to obtain the total radioactivity in the organ, and by using small VOIs to measure the tissue radioactivity concentration. During the first treatment session in 24 patients, imaging was performed 1, 24, 96 and 168 h after [177Lu-DOTA0, Tyr3]octreotate infusion. Absorbed doses in non tumour-affected kidney, liver and spleen were calculated and compared for all three methods (planar imaging, SPECT organ VOIs, SPECT small VOIs).Results
Planar and SPECT dosimetry were comparable in areas free of tumours, but due to overlap the planar dosimetry highly overestimated the absorbed dose in organs with tumours. Furthermore, SPECT dosimetry based on small VOIs proved to be more reliable than whole-organ dosimetry.Conclusion
We conclude that SPECT dosimetry based on small VOIs is feasible and more accurate than conventional planar dosimetry, and thus may contribute towards optimising targeted radionuclide therapy. 相似文献14.
Dik J. Kwekkeboom Willem H. Bakker Peter P. Kooij Mark W. Konijnenberg Ananth Srinivasan Jack L. Erion Michelle A. Schmidt Joe L. Bugaj Marion de Jong Eric P. Krenning 《European journal of nuclear medicine and molecular imaging》2001,28(9):1319-1325
The somatostatin analogue [DOTA0,Tyr3]octreotate has a nine-fold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA0,Tyr3]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide lutetium-177, this compound has been shown to have a very favourable impact on tumour regression and animal survival in a rat model. Because of these reported advantages over the analogues currently used for somatostatin receptor-mediated radiotherapy, we decided to compare [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) with [111In-DTPA0]octreotide (111In-octreotide) in six patients with somatostatin receptor-positive tumours. Plasma radioactivity after 177Lu-octreotate expressed as a percentage of the injected dose was comparable with that after 111In-octreotide. Urinary excretion of radioactivity was significantly lower than after 111In-octreotide, averaging 64% after 24 h. The uptake after 24 h, expressed as a percentage of the injected dose of 177Lu-octreotate, was comparable to that after 111In-octreotide for kidneys, spleen and liver, but was three- to fourfold higher for four of five tumours. The spleen and kidneys received the highest absorbed doses. The doses to the kidneys were reduced by a mean of 47% after co-infusion of amino acids. It is concluded that in comparison with the radionuclide-coupled somatostatin analogues that are currently available for somatostatin receptor-mediated radiotherapy, 177Lu-octreotate potentially represents an important improvement. Higher absorbed doses can be achieved to most tumours, with about equal doses to potentially dose-limiting organs; furthermore, the lower tissue penetration range of 177Lu as compared with 90Y may be especially important for small tumours. 相似文献
15.
Naum A Tuunanen H Engblom E Oikonen V Sipilä H Iozzo P Nuutila P Knuuti J 《European journal of nuclear medicine and molecular imaging》2007,34(4):563-572
Purpose This study sought to evaluate an imaging approach using [15O]H2O and positron emission tomography (PET) for simultaneous assessment of myocardial perfusion, cardiac function and lung water
content as a potential indicator of pulmonary oedema.
Methods Twenty-six subjects divided into two groups (group I, 13 patients with idiopathic dilated cardiomyopathy; group II, 13 healthy
volunteers) underwent dynamic PET scanning after intravenous infusion of ≈995 MBq [15O]H2O. In both groups, echocardiograms were performed after the PET studies. From the dynamic [15O]H2O data, lung water content (LWC) at equilibrium, myocardial blood flow (MBF), cardiac output (CO), stroke volume (SV) and
stroke volume indexes (SVI) using the indicator dilution principle were determined.
Results LWC was 18% (p = 0.038) higher in patients than in controls. Global MBF did not differ significantly between the groups, but regional MBF
values were significantly lower (p < 0.05) in the anterior and septal walls in the patient group. The results of the Passing-Bablok regression indicated the
absence of a systematic difference between the two techniques. Bland-Altman analysis performed for each group (patients vs
healthy controls) showed a non-significant bias (p > 0.1) of −0.02 ± 0.82 vs −0.05 ± 0.54 l/min (CO), −1.44 ± 14.31 vs 1.70 ± 10.56 ml/beat (SV) and 0.47 ± 6.21 vs 0.30 ± 5.02 ml/beat/m2 (SVI). The 95% limits of agreement were −1.62 to 1.59 vs −1.11 to 1.01 l/min (CO), −26.61 to 29.49 vs −22.39 to 18.99 ml/beat
(SV) and −11.69 to 12.88 vs −9.53 to 10.14 ml/beat/m2 (SVI). Right ventricular CO was increased by 33% (p = 0.014) in the patient group as compared with normal controls.
Conclusion Our results demonstrate that additional analysis of cardiac function and lung water content are feasible from the dynamic
cardiac [15O]H2O PET studies acquired for myocardial perfusion. The parameters appear to work as expected. Further studies are warranted
to elucidate the clinical value of these new parameters.
This study was financially supported by grants from Turku University Hospital (EVO) and Finnish Foundation for Cardiovascular
Research. 相似文献
16.
Povoski SP Sarikaya I White WC Marsh SG Hall NC Hinkle GH Martin EW Knopp MV 《European journal of nuclear medicine and molecular imaging》2008,35(11):2026-2034
Purpose The purpose of the current study was to comprehensively evaluate occupational radiation exposure to all intraoperative and
perioperative personnel involved in radioguided surgical procedures utilizing 18F-fluorodeoxyglucose (18F-FDG).
Methods Radiation exposure to surgeon, anesthetist, scrub technologist, circulating nurse, preoperative nurse, and postoperative nurse,
using aluminum oxide dosimeters read by optically stimulated luminescence technology, was evaluated during ten actual radioguided
surgical procedures involving administration of 18F-FDG.
Results Mean patient dosage of 18F-FDG was 699 ± 181 MBq (range 451–984). Mean time from 18F-FDG injection to initial exposure of personnel to the patient was shortest for the preoperative nurse (75 ± 63 min, range
0–182) followed by the circulating nurse, anesthetist, scrub technologist, surgeon, and postoperative nurse. Mean total time
of exposure of the personnel to the patient was longest for the anesthetist (250 ± 128 min, range 69–492) followed by the
circulating nurse, scrub technologist, surgeon, postoperative nurse, and preoperative nurse. Largest deep dose equivalent
per case was received by the surgeon (164 ± 135 μSv, range 10–580) followed by the anesthetist, scrub technologist, postoperative
nurse, circulating nurse, and preoperative nurse. Largest deep dose equivalent per hour of exposure was received by the preoperative
nurse (83 ± 134 μSv/h, range 0–400) followed by the surgeon, anesthetist, postoperative nurse, scrub technologist, and circulating
nurse.
Conclusion On a per case basis, occupational radiation exposure to intraoperative and perioperative personnel involved in 18F-FDG radioguided surgical procedures is relatively small. Development of guidelines for monitoring occupational radiation
exposure in 18F-FDG cases will provide reassurance and afford a safe work environment for such personnel. 相似文献
17.
Breeman WA De Jong M Visser TJ Erion JL Krenning EP 《European journal of nuclear medicine and molecular imaging》2003,30(6):917-920
DOTA-conjugated peptides, such as [DOTA(0),Tyr(3)]octreotide (DOTATOC) and [DOTA(0),Tyr(3)]octreotate (DOTA-tate), can be labelled with radionuclides such as (90)Y, (111)In and (177)Lu. These radiolabelled somatostatin analogues are used for peptide receptor radionuclide therapy (PRRT). Radioligands for PRRT require high specific activities. However, although these radionuclides are produced without addition of carrier, contaminants are introduced during production and as decay products. In this study, parameters influencing the kinetics of labelling of DOTA-peptides were investigated and conditions were optimised to obtain the highest achievable specific activity. The effects of contaminants were systematically investigated, concentration dependently, in a test model mimicking conditions for labelling with minimal molar excess of DOTA-peptides over radionuclide. Kinetics of labelling of DOTA-peptides were optimal at pH 4-4.5; pH <4 strongly slowed down the kinetics. Above pH 5, reaction kinetics varied owing to the formation of radionuclide hydroxides. Labelling with (90)Y and (177)Lu was completed after 20 min at 80 degrees C, while labelling with (111)In was completed after 30 min at 100 degrees C. The effects of contaminants were systematically categorised, e.g. Cd(2+) is the target and decay product of (111)In, and it was found to be a strong competitor with (111)In for incorporation in DOTA. In contrast, Zr(4+) and Hf(4+), decay products of (90)Y and (177)Lu, respectively, did not interfere with the incorporation of these radionuclides. The following conclusions are drawn: (a) DOTA-peptides can be radiolabelled at high specific activity; (b) reaction kinetics differ for each radionuclide; and (c) reactions can be hampered by contaminants, such as target material and decay products. 相似文献
18.
Takano A Gulyás B Varrone A Karlsson P Schou M Airaksinen AJ Vandenhende F Tauscher J Halldin C 《European journal of nuclear medicine and molecular imaging》2008,35(1):153-157
Introduction (S,S)-[18F]FMeNER-D2 is a recently developed positron emission tomography (PET) ligand for in vivo quantification of norepinephrine transporter.
A monkey occupancy study with the radioligand indicated that (S,S)-[18F]FMeNER-D2 can be useful for quantitative PET analysis. In this preliminary study, regional distributions in the living human brain
were evaluated.
Materials and methods Brain PET measurements were performed for a total of 255 min after the injection of 188.3 ± 5.7 MBq of (S,S)-[18F]FMeNER-D2 in four healthy male subjects. Regions of interests were drawn on the thalamus and the caudate in the coregistered MRI/PET
images.
Results (S,S)-[18F]FMeNER-D2 displayed good brain penetration and selective retention in regions rich in norepinephrine reuptake sites. The transient
peak equilibrium was reached during the PET measurements. The ratios of radioactivity uptake in the thalamus to that in the
caudate were 1.50 ± 0.06 for the time period of 90–255 min.
Conclusion The present preliminary investigation indicates that (S,S)-[18F]FMeNER-D2 has suitable characteristics for probing the norepinephrine reuptake system with PET in the human brain. 相似文献
19.
Hendrik Bergsma Mark W. Konijnenberg Boen L. R. Kam Jaap J. M. Teunissen Peter P. Kooij Wouter W. de Herder Gaston J. H. Franssen Casper H. J. van Eijck Eric P. Krenning Dik J. Kwekkeboom 《European journal of nuclear medicine and molecular imaging》2016,43(3):453-463
Purpose
In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from 131I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit.Methods
The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined.Results
Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0?×?109/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67?±?7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq 177Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients.Conclusion
The incidence of subacute haematological toxicity after PRRT with 177Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from 131I, seems not to be valid for PRRT with 177Lu-DOTATATE.20.
Breeman WA van der Wansem K Bernard BF van Gameren A Erion JL Visser TJ Krenning EP de Jong M 《European journal of nuclear medicine and molecular imaging》2003,30(2):312-315
Peptide receptor-targeted radionuclide therapy is nowadays also being performed with DOTA-conjugated peptides, such as [DOTA(0),Tyr(3)]octreotate, labelled with radionuclides like (177)Lu. The incorporation of (177)Lu is typically >/=99.5%; however, since a total patient dose can be as high as 800 mCi, the amount of free (177)Lu(3+) (= non-DOTA-incorporated) can be substantial. Free (177)Lu(3+) accumulates in bone with unwanted irradiation of bone marrow as a consequence. (177)Lu-DTPA is reported to be stable in serum in vitro, and in vivo it has rapid renal excretion. Transforming free Lu(3+) to Lu-DTPA might reroute this fraction from accumulation in bone to renal clearance. We therefore investigated: (a) the biodistribution in rats of (177)LuCl(3), [(177)Lu-DOTA(0),Tyr(3)]octreotate and (177)Lu-DTPA; (b) the possibilities of complexing the free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate to (177)Lu-DTPA prior to intravenous injection; and (c) the effects of free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate, in the presence and absence of DTPA, on the biodistribution in rats. (177)LuCl(3) had high skeletal uptake (i.e. 5% ID per gram femur, with localization mainly in the epiphyseal plates) and a 24-h total body retention of 80% injected dose (ID). [(177)Lu-DOTA(0),Tyr(3)]octreotate had high and specific uptake in somatostatin receptor-positive tissues, and 24-h total body retention of 19% ID. (177)Lu-DTPA had rapid renal clearance, and 24-h total body retention of 4% ID. Free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate could be complexed to (177)Lu-DTPA. Accumulation of (177)Lu in femur, blood, liver and spleen showed a dose relation to the amount of free (177)Lu(3+), while these accumulations could be normalized by the addition of DTPA. After labelling [DOTA(0),Tyr(3)]octreotate with (177)Lu the addition of DTPA prior to intravenous administration of [(177)Lu-DOTA(0),Tyr(3)]octreotate is strongly recommended. 相似文献