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Peter Caravan - One of the best experts on this subject based on the ideXlab platform.
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Yttrium 86 is a positron emitting surrogate of gadolinium for noninvasive quantification of whole body distribution of gadolinium based contrast agents
Angewandte Chemie, 2020Co-Authors: Mariane Le Fur, Nicholas J Rotile, Carlos Correcher, Veronica Clavijo Jordan, Alana Ross, Ciprian Catana, Peter CaravanAbstract:Gadolinium-based contrast agents (GBCAs) are used to provide diagnostic information in clinical magnetic resonance (MR) examinations. Gadolinium (Gd) has been detected in the brain, bone and skin of patients, months and years following GBCA administration, raising concerns about long term toxicity. Despite increased scrutiny, the concentration, chemical form and fate of the retained gadolinium species remain unknown. Importantly, the whole body biodistribution and organ clearance of GBCAs is poorly understood in humans. Gadolinium lacks suitable isotopes for nuclear imaging. We demonstrate that the Yttrium-86 isotope can be used as a gadolinium surrogate. We show that Gd and their analogous Y complexes have similar properties both in solution and in vivo, and that Yttrium-86 PET can be used to track the biodistribution of GBCAs over a two-day period.
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Yttrium 86 pet imaging in rodents to better understand the biodistribution and clearance of gadolinium based contrast agents used in mri
The Journal of Nuclear Medicine, 2019Co-Authors: Mariane Le Fur, Nicholas J Rotile, Veronica Clavijo Jordan, Alana Ross, Ciprian Catana, Peter CaravanAbstract:346 Objectives: Gadolinium-based contrast agents (GBCAs) have been used in combination with MRI for more than three decades1 and are considered extremely safe. However, trace amounts of gadolinium have been detected in the skin and central nervous system of patients with normal renal function, months to years after administration of a GBCA.2 The biodistribution and clearance of the commercially available GBCAs as well as the chemical form of the retained gadolinium species remain to be fully understood.3 Yttrium(III) and Gd(III) have very similar ionic radii leading to very similar chemical behavior. The objective of this work was to determine if Y-86 (t1/2 = 14.7h, 31.9% β+) could serve as a PET imaging reporter for Gd in GBCAs. Methods: Biodistribution study in mice. An equimolar solution of Y-DTPA and Gd-DTPA complexes at pH 7 was prepared and the absence of free Y3+ or Gd3+ was confirmed by HPLC coupled to ICP-MS. 6 mice were administered, by IV injection, a dose of Y/Gd-DTPA at 0.6 mmol/kg and sacrificed 7 days after injection. 21 organs and tissues were collected and digested in nitric acid with dysprosium used as an internal standard. Y and Gd concentration were measured by ICP-MS. 86Y Radiolabeling. DTPA was incubated with 86YCl3 in sodium citrate buffer at pH 6 at 80°C. After 15 minutes, the quantitative labeling was confirmed by radioHPLC using an HILIC column. The solution was purified on a chelex column and filtered through a 0.2 μm filter. PET/MR imaging and biodistribution in rats. 4 rats were administered, by IV injection, a microdose of 86Y-DTPA (135-157 μCi) mixed with a commercial solution of Gd-DTPA at 0.6 mmol/kg and scanned 7 to 11h and 52 to 56h after injection. After the last scan, rats were sacrificed, and the organs collected. The counts in each organ were measured using a Wizard gamma counter. The organs were then digested in nitric acid and the Gd concentration measured by ICP-MS. Results: 7 days after the concomitant injection of 0.6 mmol/kg Y-DTPA/Gd-DTPA in mice, the Yttrium and gadolinium concentration per organ or tissues were very similar, Figure 1A, with no statistically significant differences and the Y:Gd ratio was close to 1 demonstrating very similar in vivo behavior of the two complexes, Figure 1B. The highest concentration was detected in the kidneys (Figure 1A). DTPA was quantitatively labeled with Yttrium-86. PET-MR imaging of rats 56h after injection of 86Y-DTPA/Gd-DTPA demonstrated that the residual contrast agent in the kidneys could be detected by PET. ICP-MS of digested kidney revealed a similar concentration of Gd as predicted by the measurement of radioactivity. Conclusions: Y3+ can be used as a surrogate for Gd3+ in GBCAs. Yttrium-86 labeled GBCAs represents a useful new tool to study the whole body distribution and elimination of GBCAs over a 2 to 3 day period after administration. Research support. National Institute for Biomedical Imaging and Bioengineering for funding (EB009062). 1) J. Wahsner, E. M. Gale, A. Rodriguez-Rodriguez and P. Caravan, Chem. Rev., 2018, Article ASAP. 2) R. J. McDonald, D. Levine et al. Radiology, 2018, 289, 517-534. 3) M. Le Fur and P. Caravan, Metallomics, 2019, Advance Article. Figure 1: Biodistribution in mice. A) Amount of retained gadolinium and Yttrium measured in the harvested organs and tissues, expressed in nmol of Gd per gram of wet tissue, 7 days after injection of a solution of Gd-DTPA and Y-DTPA at 0.6 mmol/kg. [asterisk]The amount of Gd and Y measured in the blood was below the limit of quantification. B) Y to Gd ratio in the harvested organs and tissues calculated from the Y and Gd concentrations (nmol/g) after injection of Y/Gd-DTPA. The red dashed lines correspond to the mean ratio. Figure 2: A) MR images of a rat 56h after injection of a mixture of 86Y-DTPA (153 μCi) and Magnevist (0.6 mmol/kg). B) PET images are superimposed to the MR images. The crosshairs show the position of the right kidney.
Mariane Le Fur - One of the best experts on this subject based on the ideXlab platform.
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Yttrium 86 is a positron emitting surrogate of gadolinium for noninvasive quantification of whole body distribution of gadolinium based contrast agents
Angewandte Chemie, 2020Co-Authors: Mariane Le Fur, Nicholas J Rotile, Carlos Correcher, Veronica Clavijo Jordan, Alana Ross, Ciprian Catana, Peter CaravanAbstract:Gadolinium-based contrast agents (GBCAs) are used to provide diagnostic information in clinical magnetic resonance (MR) examinations. Gadolinium (Gd) has been detected in the brain, bone and skin of patients, months and years following GBCA administration, raising concerns about long term toxicity. Despite increased scrutiny, the concentration, chemical form and fate of the retained gadolinium species remain unknown. Importantly, the whole body biodistribution and organ clearance of GBCAs is poorly understood in humans. Gadolinium lacks suitable isotopes for nuclear imaging. We demonstrate that the Yttrium-86 isotope can be used as a gadolinium surrogate. We show that Gd and their analogous Y complexes have similar properties both in solution and in vivo, and that Yttrium-86 PET can be used to track the biodistribution of GBCAs over a two-day period.
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Yttrium 86 pet imaging in rodents to better understand the biodistribution and clearance of gadolinium based contrast agents used in mri
The Journal of Nuclear Medicine, 2019Co-Authors: Mariane Le Fur, Nicholas J Rotile, Veronica Clavijo Jordan, Alana Ross, Ciprian Catana, Peter CaravanAbstract:346 Objectives: Gadolinium-based contrast agents (GBCAs) have been used in combination with MRI for more than three decades1 and are considered extremely safe. However, trace amounts of gadolinium have been detected in the skin and central nervous system of patients with normal renal function, months to years after administration of a GBCA.2 The biodistribution and clearance of the commercially available GBCAs as well as the chemical form of the retained gadolinium species remain to be fully understood.3 Yttrium(III) and Gd(III) have very similar ionic radii leading to very similar chemical behavior. The objective of this work was to determine if Y-86 (t1/2 = 14.7h, 31.9% β+) could serve as a PET imaging reporter for Gd in GBCAs. Methods: Biodistribution study in mice. An equimolar solution of Y-DTPA and Gd-DTPA complexes at pH 7 was prepared and the absence of free Y3+ or Gd3+ was confirmed by HPLC coupled to ICP-MS. 6 mice were administered, by IV injection, a dose of Y/Gd-DTPA at 0.6 mmol/kg and sacrificed 7 days after injection. 21 organs and tissues were collected and digested in nitric acid with dysprosium used as an internal standard. Y and Gd concentration were measured by ICP-MS. 86Y Radiolabeling. DTPA was incubated with 86YCl3 in sodium citrate buffer at pH 6 at 80°C. After 15 minutes, the quantitative labeling was confirmed by radioHPLC using an HILIC column. The solution was purified on a chelex column and filtered through a 0.2 μm filter. PET/MR imaging and biodistribution in rats. 4 rats were administered, by IV injection, a microdose of 86Y-DTPA (135-157 μCi) mixed with a commercial solution of Gd-DTPA at 0.6 mmol/kg and scanned 7 to 11h and 52 to 56h after injection. After the last scan, rats were sacrificed, and the organs collected. The counts in each organ were measured using a Wizard gamma counter. The organs were then digested in nitric acid and the Gd concentration measured by ICP-MS. Results: 7 days after the concomitant injection of 0.6 mmol/kg Y-DTPA/Gd-DTPA in mice, the Yttrium and gadolinium concentration per organ or tissues were very similar, Figure 1A, with no statistically significant differences and the Y:Gd ratio was close to 1 demonstrating very similar in vivo behavior of the two complexes, Figure 1B. The highest concentration was detected in the kidneys (Figure 1A). DTPA was quantitatively labeled with Yttrium-86. PET-MR imaging of rats 56h after injection of 86Y-DTPA/Gd-DTPA demonstrated that the residual contrast agent in the kidneys could be detected by PET. ICP-MS of digested kidney revealed a similar concentration of Gd as predicted by the measurement of radioactivity. Conclusions: Y3+ can be used as a surrogate for Gd3+ in GBCAs. Yttrium-86 labeled GBCAs represents a useful new tool to study the whole body distribution and elimination of GBCAs over a 2 to 3 day period after administration. Research support. National Institute for Biomedical Imaging and Bioengineering for funding (EB009062). 1) J. Wahsner, E. M. Gale, A. Rodriguez-Rodriguez and P. Caravan, Chem. Rev., 2018, Article ASAP. 2) R. J. McDonald, D. Levine et al. Radiology, 2018, 289, 517-534. 3) M. Le Fur and P. Caravan, Metallomics, 2019, Advance Article. Figure 1: Biodistribution in mice. A) Amount of retained gadolinium and Yttrium measured in the harvested organs and tissues, expressed in nmol of Gd per gram of wet tissue, 7 days after injection of a solution of Gd-DTPA and Y-DTPA at 0.6 mmol/kg. [asterisk]The amount of Gd and Y measured in the blood was below the limit of quantification. B) Y to Gd ratio in the harvested organs and tissues calculated from the Y and Gd concentrations (nmol/g) after injection of Y/Gd-DTPA. The red dashed lines correspond to the mean ratio. Figure 2: A) MR images of a rat 56h after injection of a mixture of 86Y-DTPA (153 μCi) and Magnevist (0.6 mmol/kg). B) PET images are superimposed to the MR images. The crosshairs show the position of the right kidney.
Hans Herzog - One of the best experts on this subject based on the ideXlab platform.
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radiation dose calculation of analogous Yttrium 90 radiotherapeutics measurement of pharmacokinetics of Yttrium 86 radiopharmaceuticals with pet and
2014Co-Authors: Hans Herzog, Frank Rosch, G Stocklin, Christoph Lueders, Syed M Qaim, L E FeinendegenAbstract:J Nucl Med. Hans Herzog, Frank Rosch, Gerhard Stocklin, Christoph Lueders, Syed M. Qaim and Ludwig E. Feinendegen Radiation Dose Calculation of Analogous Yttrium-90 Radiotherapeutics Measurement of Pharmacokinetics of Yttrium-86 Radiopharmaceuticals with PET and http://jnm.snmjournals.org/content/34/12/2222 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml Information about reproducing figures, tables, or other portions of this article can be found online at:
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pet imaging with Yttrium 86 comparison of phantom measurements acquired with different pet scanners before and after applying background subtraction
European Journal of Nuclear Medicine and Molecular Imaging, 2003Co-Authors: Hansgeorg Buchholz, Frank Rosch, Hans Herzog, Gregor J Forster, Helmut Reber, O Nickel, Peter BartensteinAbstract:Quantitative imaging with the positron emitter 86Y is the method of choice to determine the uptake and dosimetry of 90Y-labelled radiopharmaceuticals. To examine the quantitative accuracy of positron emission tomography findings with 86Y, this non-pure positron emitter was evaluated in a cylindrical phantom with rods of Teflon, water and air and measured with three different scanners: ECAT EXACT (2D/3D), ECAT HR+ (2D/3D) and PC4096+ (2D). After standard reconstruction, 86Y radioactivity measured with the ECAT EXACT and related to the true radioactivity varied between 0.84 and 0.99 in 2D and between 0.93 and 1.20 in 3D from the first to the last acquisition (eight half-life times later). The water and Teflon rods exhibited considerable amounts of reconstructed radioactivity—21% in 2D and 67% in 3D for water and 65% and 147%, respectively, for Teflon—compared with the actual 86Y radioactivity of the phantom. For the ECAT HR+ similar results were obtained in 3D, but there were even greater overestimations in 2D. Measurements with the PC4096+ showed rather small errors, with 10% for water and 20% for Teflon. To correct for the background of γ-coincidences, sinograms were analysed and an experimental percentage of the background was subtracted from the sinograms. In order to minimise the errors in reconstructed radioactivity, the subtraction value had to be different for the individual scanners and modes. Our results demonstrate that 90Y/86Y-based dosimetry for bone and red marrow must be regarded with caution if it is derived from regions of interest over the bone, the density of which is similar to that of Teflon. To obtain more reliable estimates, an appropriate background correction must be applied and tailored individually with respect to the scanner and acquisition mode.
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radiation doses of Yttrium 90 citrate and Yttrium 90 edtmp as determined via analogous Yttrium 86 complexes and positron emission tomography
European Journal of Nuclear Medicine and Molecular Imaging, 1996Co-Authors: Frank Rosch, Hans Herzog, C Plag, Bernd Neumaier, U Braun, H W Mullergartner, G StocklinAbstract:Yttrium-90 is used for palliative therapy for the treatment of skeletal metastases, but because it is a pure beta- emitter, data on the pharmacokinetics and radiation doses to metastases and unaffected organs are lacking. To obtain such data, the present study employed Yttrium-86 as a substitute for 90Y, with detection by positron emission tomography (PET). The study compared the properties of two different 86Y complexes - 86Y-citrate and 86Y-ethylene diamine tetramethylene phosphonate (EDTMP) - in ten patients with prostatic cancer who had developed multiple bone metastases (the ten patients being divided into two groups of five). Early dynamics were measured up to 1 h post injection (p.i.) over the liver region, followed by subsequent whole-body PET scans up to 3 days p.i. Absolute uptake data were determined for normal bone, bone metastases, liver and kidney. Radiation doses were calculated according to the MIRD recommendations. Based on the pharmacokinetic measurements of the distribution of the 86Y complexes, it was possible to calculate radiation doses for the bone metastases and the red bone marrow delivered by complexes containing 90Y. In 1 cm3 of bone metastasis, doses of 26+/-11 mGy/MBq and 18+/-2 mGy/MBq were determined per MBq of injected 90Y-citrate and 90Y-EDTMP, respectively. The doses to the bone marrow were 2.5+/-0.4 mGy/MBq for 90Y-citrate and 1.8+/-0.6 mGy/MBq for 90Y-EDTMP. 86Y and PET provide quantitative information applicable to the clinical use of 90Y. This method may also be useful for the design of other 90Y radiopharmaceuticals and for planning radiotherapy dosages.
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measurement of pharmacokinetics of Yttrium 86 radiopharmaceuticals with pet and radiation dose calculation of analogous Yttrium 90 radiotherapeutics
The Journal of Nuclear Medicine, 1993Co-Authors: Hans Herzog, Frank Rosch, G Stocklin, Christoph Lueders, Syed M Qaim, L E FeinendegenAbstract:This study was performed to demonstrate the quantitative in vivo assessment of human pharmacokinetics of 90Y-radiotherapeutics using the positron-emitting substitute 86Y and PET. This technique is illustrated in a patient with disseminated bone metastases from breast cancer who was injected with 100 MBq of 86Y-citrate as an analog of the commercially available radiotherapeutic 90Y-citrate. Whole-body distribution was measured with a PET camera 4, 10, 21, 28 and 45 hr postinjection. Uptake data were determined from reconstructed transverse PET images by regions of interest placed in normal bone tissue, liver and metastases. Images of coronal and sagittal whole-body sections were obtained by reformatting the transverse PET images. The ratio of activity concentration in metastases to that in normal bone ranged from 1.5:1 to 3.5:1. Of the injected tracer, 13.4% was found in the skeleton and 0.43% in the metastasis with the highest 86Y concentration. Radiation doses per 1 MBq of injected 90Y-citrate were calculated from 86Y-citrate data and data from MIRD pamphlets 5 and 11. The doses were 1.01 MGy/MBq for red marrow, 593 microGy/MBq for the liver and approximately 3.5 MGy/MBq for the most conspicuous metastases. This study demonstrates that the use of PET via 86Y allows an individual in vivo quantification of activity uptake and radiation dose of both normal tissue and tumor in pain treatment with 90Y-labeled radiotherapeutics.
Frank Rosch - One of the best experts on this subject based on the ideXlab platform.
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radiation dose calculation of analogous Yttrium 90 radiotherapeutics measurement of pharmacokinetics of Yttrium 86 radiopharmaceuticals with pet and
2014Co-Authors: Hans Herzog, Frank Rosch, G Stocklin, Christoph Lueders, Syed M Qaim, L E FeinendegenAbstract:J Nucl Med. Hans Herzog, Frank Rosch, Gerhard Stocklin, Christoph Lueders, Syed M. Qaim and Ludwig E. Feinendegen Radiation Dose Calculation of Analogous Yttrium-90 Radiotherapeutics Measurement of Pharmacokinetics of Yttrium-86 Radiopharmaceuticals with PET and http://jnm.snmjournals.org/content/34/12/2222 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml Information about reproducing figures, tables, or other portions of this article can be found online at:
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pet imaging with Yttrium 86 comparison of phantom measurements acquired with different pet scanners before and after applying background subtraction
European Journal of Nuclear Medicine and Molecular Imaging, 2003Co-Authors: Hansgeorg Buchholz, Frank Rosch, Hans Herzog, Gregor J Forster, Helmut Reber, O Nickel, Peter BartensteinAbstract:Quantitative imaging with the positron emitter 86Y is the method of choice to determine the uptake and dosimetry of 90Y-labelled radiopharmaceuticals. To examine the quantitative accuracy of positron emission tomography findings with 86Y, this non-pure positron emitter was evaluated in a cylindrical phantom with rods of Teflon, water and air and measured with three different scanners: ECAT EXACT (2D/3D), ECAT HR+ (2D/3D) and PC4096+ (2D). After standard reconstruction, 86Y radioactivity measured with the ECAT EXACT and related to the true radioactivity varied between 0.84 and 0.99 in 2D and between 0.93 and 1.20 in 3D from the first to the last acquisition (eight half-life times later). The water and Teflon rods exhibited considerable amounts of reconstructed radioactivity—21% in 2D and 67% in 3D for water and 65% and 147%, respectively, for Teflon—compared with the actual 86Y radioactivity of the phantom. For the ECAT HR+ similar results were obtained in 3D, but there were even greater overestimations in 2D. Measurements with the PC4096+ showed rather small errors, with 10% for water and 20% for Teflon. To correct for the background of γ-coincidences, sinograms were analysed and an experimental percentage of the background was subtracted from the sinograms. In order to minimise the errors in reconstructed radioactivity, the subtraction value had to be different for the individual scanners and modes. Our results demonstrate that 90Y/86Y-based dosimetry for bone and red marrow must be regarded with caution if it is derived from regions of interest over the bone, the density of which is similar to that of Teflon. To obtain more reliable estimates, an appropriate background correction must be applied and tailored individually with respect to the scanner and acquisition mode.
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electrochemical separation and purification of Yttrium 86
Radiochimica Acta, 2002Co-Authors: G Reischl, Frank Rosch, Hans Jurgen MachullaAbstract:For quantitative determination of in vivo dosimetry of 9 0 Y-labeled radiotherapeuticals by means of PET, the positron emitting analogue Yttrium-86 was produced at a low energy ("medical") cyclotron via the known 8 6 Sr(p,n) 8 6 Y reaction. Using 200 mg of 8 6 SrCO 3 (enrichment 95.6%) and protons of 15.1 MeV energy, average yields of 8 6 Y of 48′8 MBq/μA h n were produced. After dissolution of 8 6 SrCO 3 in 3 ml of 0.6 N HNO 3 , 8 6 Y was deposited in a simple and highly efficient electrochemical two-step procedure onto a platinum cathode at 450 mA (= 20 mA/cm 2 ). The isotope was finally removed from the electrode by 100-300 μl of 0.5-1.0 N HCl or 0.3-0.6 N HNO, resulting in an overall recovery of 88 ′ 6% (corrected for decay). Up to I GBq of 8 6 Y with high radionuclidic and radiochemical purity were obtained after a 2.5 h irradiation and a radiochemical separation time of 2 h. An ICP/AES analysis of the separated fraction showed a very small amount of strontium (< 0.1 ppm). The chemical purity of 8 6 Y, essential for efficient labeling, was successfully demonstrated by means of complex formation with DOTA and a DOTA-conjugated peptide, exhibiting labeling yields higher than 98%.
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radiation doses of Yttrium 90 citrate and Yttrium 90 edtmp as determined via analogous Yttrium 86 complexes and positron emission tomography
European Journal of Nuclear Medicine and Molecular Imaging, 1996Co-Authors: Frank Rosch, Hans Herzog, C Plag, Bernd Neumaier, U Braun, H W Mullergartner, G StocklinAbstract:Yttrium-90 is used for palliative therapy for the treatment of skeletal metastases, but because it is a pure beta- emitter, data on the pharmacokinetics and radiation doses to metastases and unaffected organs are lacking. To obtain such data, the present study employed Yttrium-86 as a substitute for 90Y, with detection by positron emission tomography (PET). The study compared the properties of two different 86Y complexes - 86Y-citrate and 86Y-ethylene diamine tetramethylene phosphonate (EDTMP) - in ten patients with prostatic cancer who had developed multiple bone metastases (the ten patients being divided into two groups of five). Early dynamics were measured up to 1 h post injection (p.i.) over the liver region, followed by subsequent whole-body PET scans up to 3 days p.i. Absolute uptake data were determined for normal bone, bone metastases, liver and kidney. Radiation doses were calculated according to the MIRD recommendations. Based on the pharmacokinetic measurements of the distribution of the 86Y complexes, it was possible to calculate radiation doses for the bone metastases and the red bone marrow delivered by complexes containing 90Y. In 1 cm3 of bone metastasis, doses of 26+/-11 mGy/MBq and 18+/-2 mGy/MBq were determined per MBq of injected 90Y-citrate and 90Y-EDTMP, respectively. The doses to the bone marrow were 2.5+/-0.4 mGy/MBq for 90Y-citrate and 1.8+/-0.6 mGy/MBq for 90Y-EDTMP. 86Y and PET provide quantitative information applicable to the clinical use of 90Y. This method may also be useful for the design of other 90Y radiopharmaceuticals and for planning radiotherapy dosages.
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measurement of pharmacokinetics of Yttrium 86 radiopharmaceuticals with pet and radiation dose calculation of analogous Yttrium 90 radiotherapeutics
The Journal of Nuclear Medicine, 1993Co-Authors: Hans Herzog, Frank Rosch, G Stocklin, Christoph Lueders, Syed M Qaim, L E FeinendegenAbstract:This study was performed to demonstrate the quantitative in vivo assessment of human pharmacokinetics of 90Y-radiotherapeutics using the positron-emitting substitute 86Y and PET. This technique is illustrated in a patient with disseminated bone metastases from breast cancer who was injected with 100 MBq of 86Y-citrate as an analog of the commercially available radiotherapeutic 90Y-citrate. Whole-body distribution was measured with a PET camera 4, 10, 21, 28 and 45 hr postinjection. Uptake data were determined from reconstructed transverse PET images by regions of interest placed in normal bone tissue, liver and metastases. Images of coronal and sagittal whole-body sections were obtained by reformatting the transverse PET images. The ratio of activity concentration in metastases to that in normal bone ranged from 1.5:1 to 3.5:1. Of the injected tracer, 13.4% was found in the skeleton and 0.43% in the metastasis with the highest 86Y concentration. Radiation doses per 1 MBq of injected 90Y-citrate were calculated from 86Y-citrate data and data from MIRD pamphlets 5 and 11. The doses were 1.01 MGy/MBq for red marrow, 593 microGy/MBq for the liver and approximately 3.5 MGy/MBq for the most conspicuous metastases. This study demonstrates that the use of PET via 86Y allows an individual in vivo quantification of activity uptake and radiation dose of both normal tissue and tumor in pain treatment with 90Y-labeled radiotherapeutics.
Nicholas J Rotile - One of the best experts on this subject based on the ideXlab platform.
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Yttrium 86 is a positron emitting surrogate of gadolinium for noninvasive quantification of whole body distribution of gadolinium based contrast agents
Angewandte Chemie, 2020Co-Authors: Mariane Le Fur, Nicholas J Rotile, Carlos Correcher, Veronica Clavijo Jordan, Alana Ross, Ciprian Catana, Peter CaravanAbstract:Gadolinium-based contrast agents (GBCAs) are used to provide diagnostic information in clinical magnetic resonance (MR) examinations. Gadolinium (Gd) has been detected in the brain, bone and skin of patients, months and years following GBCA administration, raising concerns about long term toxicity. Despite increased scrutiny, the concentration, chemical form and fate of the retained gadolinium species remain unknown. Importantly, the whole body biodistribution and organ clearance of GBCAs is poorly understood in humans. Gadolinium lacks suitable isotopes for nuclear imaging. We demonstrate that the Yttrium-86 isotope can be used as a gadolinium surrogate. We show that Gd and their analogous Y complexes have similar properties both in solution and in vivo, and that Yttrium-86 PET can be used to track the biodistribution of GBCAs over a two-day period.
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Yttrium 86 pet imaging in rodents to better understand the biodistribution and clearance of gadolinium based contrast agents used in mri
The Journal of Nuclear Medicine, 2019Co-Authors: Mariane Le Fur, Nicholas J Rotile, Veronica Clavijo Jordan, Alana Ross, Ciprian Catana, Peter CaravanAbstract:346 Objectives: Gadolinium-based contrast agents (GBCAs) have been used in combination with MRI for more than three decades1 and are considered extremely safe. However, trace amounts of gadolinium have been detected in the skin and central nervous system of patients with normal renal function, months to years after administration of a GBCA.2 The biodistribution and clearance of the commercially available GBCAs as well as the chemical form of the retained gadolinium species remain to be fully understood.3 Yttrium(III) and Gd(III) have very similar ionic radii leading to very similar chemical behavior. The objective of this work was to determine if Y-86 (t1/2 = 14.7h, 31.9% β+) could serve as a PET imaging reporter for Gd in GBCAs. Methods: Biodistribution study in mice. An equimolar solution of Y-DTPA and Gd-DTPA complexes at pH 7 was prepared and the absence of free Y3+ or Gd3+ was confirmed by HPLC coupled to ICP-MS. 6 mice were administered, by IV injection, a dose of Y/Gd-DTPA at 0.6 mmol/kg and sacrificed 7 days after injection. 21 organs and tissues were collected and digested in nitric acid with dysprosium used as an internal standard. Y and Gd concentration were measured by ICP-MS. 86Y Radiolabeling. DTPA was incubated with 86YCl3 in sodium citrate buffer at pH 6 at 80°C. After 15 minutes, the quantitative labeling was confirmed by radioHPLC using an HILIC column. The solution was purified on a chelex column and filtered through a 0.2 μm filter. PET/MR imaging and biodistribution in rats. 4 rats were administered, by IV injection, a microdose of 86Y-DTPA (135-157 μCi) mixed with a commercial solution of Gd-DTPA at 0.6 mmol/kg and scanned 7 to 11h and 52 to 56h after injection. After the last scan, rats were sacrificed, and the organs collected. The counts in each organ were measured using a Wizard gamma counter. The organs were then digested in nitric acid and the Gd concentration measured by ICP-MS. Results: 7 days after the concomitant injection of 0.6 mmol/kg Y-DTPA/Gd-DTPA in mice, the Yttrium and gadolinium concentration per organ or tissues were very similar, Figure 1A, with no statistically significant differences and the Y:Gd ratio was close to 1 demonstrating very similar in vivo behavior of the two complexes, Figure 1B. The highest concentration was detected in the kidneys (Figure 1A). DTPA was quantitatively labeled with Yttrium-86. PET-MR imaging of rats 56h after injection of 86Y-DTPA/Gd-DTPA demonstrated that the residual contrast agent in the kidneys could be detected by PET. ICP-MS of digested kidney revealed a similar concentration of Gd as predicted by the measurement of radioactivity. Conclusions: Y3+ can be used as a surrogate for Gd3+ in GBCAs. Yttrium-86 labeled GBCAs represents a useful new tool to study the whole body distribution and elimination of GBCAs over a 2 to 3 day period after administration. Research support. National Institute for Biomedical Imaging and Bioengineering for funding (EB009062). 1) J. Wahsner, E. M. Gale, A. Rodriguez-Rodriguez and P. Caravan, Chem. Rev., 2018, Article ASAP. 2) R. J. McDonald, D. Levine et al. Radiology, 2018, 289, 517-534. 3) M. Le Fur and P. Caravan, Metallomics, 2019, Advance Article. Figure 1: Biodistribution in mice. A) Amount of retained gadolinium and Yttrium measured in the harvested organs and tissues, expressed in nmol of Gd per gram of wet tissue, 7 days after injection of a solution of Gd-DTPA and Y-DTPA at 0.6 mmol/kg. [asterisk]The amount of Gd and Y measured in the blood was below the limit of quantification. B) Y to Gd ratio in the harvested organs and tissues calculated from the Y and Gd concentrations (nmol/g) after injection of Y/Gd-DTPA. The red dashed lines correspond to the mean ratio. Figure 2: A) MR images of a rat 56h after injection of a mixture of 86Y-DTPA (153 μCi) and Magnevist (0.6 mmol/kg). B) PET images are superimposed to the MR images. The crosshairs show the position of the right kidney.
