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Eric O. Aboagye - One of the best experts on this subject based on the ideXlab platform.

  • 18f icmt 11 a caspase 3 specific pet tracer for apoptosis biodistribution and radiation dosimetry
    The Journal of Nuclear Medicine, 2013
    Co-Authors: Amarnath Challapalli, Kasia Kozlowski, Laura M Kenny, William A Hallett, Giampaolo Tomasi, Mihir Gudi, Adil Alnahhas, Charles R Coombes, Eric O. Aboagye
    Abstract:

    Effective anticancer therapy induces tumor cell death through apoptosis. Noninvasive monitoring of apoptosis during therapy may provide predictive outcome information and help tailor treatment. A caspase-3–specific imaging radiotracer, 18F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin (18F-ICMT-11), has been developed for use in PET studies. We report the safety, biodistribution, and internal radiation dosimetry profiles of 18F-ICMT-11 in 8 healthy human volunteers. Methods:18F-ICMT-11 was intravenously administered as a bolus injection (mean ± SD, 159 ± 2.75 MBq; range, 154–161 MBq) to 8 healthy volunteers (4 men, 4 women). Whole-body (vertex to mid thigh) PET/CT scans were acquired at 6 time points, up to 4 h after tracer injection. Serial whole blood, plasma, and urine samples were collected for Radioactivity Measurement and radiotracer stability. In vivo 18F activities were determined from quantitative analysis of the images, and time–activity curves were generated. The total numbers of disintegrations in each organ normalized to injected activity (residence times) were calculated as the area under the curve of the time–activity curve, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using OLINDA/EXM 1.1. Results: Injection of 18F-ICMT-11 was well tolerated in all subjects, with no serious tracer-related adverse events reported. The mean effective dose averaged over both men and women was estimated to be 0.025 ± 0.004 mSv/MBq (men, 0.022 ± 0.004 mSv/MBq; women, 0.027 ± 0.004 mSv/MBq). The 5 organs receiving the highest absorbed dose (mGy/MBq), averaged over both men and women, were the gallbladder wall (0.59 ± 0.44), small intestine (0.12 ± 0.05), upper large intestinal wall (0.08 ± 0.07), urinary bladder wall (0.08 ± 0.02), and liver (0.07 ± 0.01). Elimination was both renal and via the hepatobiliary system. Conclusion:18F-ICMT-11 is a safe PET tracer with a dosimetry profile comparable to other common 18F PET tracers. These data support the further development of 18F-ICMT-11 for clinical imaging of apoptosis.

  • biodistribution and radiation dosimetry of 18f icmt 11 a caspase 3 specific pet tracer for apoptosis
    The Journal of Nuclear Medicine, 2013
    Co-Authors: Amarnath Challapalli, Kasia Kozlowski, Laura M Kenny, William A Hallett, Giampaolo Tomasi, Mihir Gudi, Adil Alnahhas, Charles Coombes, Eric O. Aboagye
    Abstract:

    161 Objectives 18F-ICMT-11, a caspase-3 specific apoptosis imaging radiotracer, has been developed for imaging by PET (1, 2). We present the first in human study of 18F-ICMT-11 that reports safety, biodistribution and internal radiation dosimetry profiles. Methods Whole body (vertex to mid-thigh) PET/CT scans of eight healthy volunteers were acquired at 6 time points, up to 4 h after 18F-ICMT-11 bolus injection (Mean±SD: 159 MBq ±2.75). Serial blood and urine samples were collected for Radioactivity Measurement. The images were quantitatively analyzed to determine in-vivo 18F activities and generate time activity curves (TACs). The total numbers of disintegrations in each organ (Residence Times: area under curve of the TAC normalized to injected activities and standard organ volumes) were calculated. Dosimetry calculations were performed using OLINDA/EXM 1.1. Results Injection of 18F-ICMT-11 was well tolerated, with no serious tracer related adverse events reported. Elimination was via the renal and hepatobiliary system. Assuming bladder voiding at 2-hrs, the 5 organs receiving the highest absorbed dose (mGy/MBq; ±SD), were the gall bladder wall (0.59±0.44), small intestine (0.12±0.05), upper large intestinal wall (0.08±0.07), urinary bladder wall (0.08±0.02), and liver (0.07±0.01). The mean effective dose and effective dose equivalent (±SD; mSv/MBq) were estimated to be 0.025±0.004 (male 0.022±0.004; female 0.027±0.004) and 0.067±0.022 (male 0.067±0.022; female 0.068±0.009), respectively. Conclusions 18F-ICMT-11 is safe, and has favorable radiation dosimetry profile for clinical imaging. This supports further evaluation of 18F-ICMT-11 to assess the magnitude of apoptosis in patients following cancer therapy.

Ronald Boellaard - One of the best experts on this subject based on the ideXlab platform.

  • radiation dosimetry of 89zr labeled chimeric monoclonal antibody u36 as used for immuno pet in head and neck cancer patients
    The Journal of Nuclear Medicine, 2009
    Co-Authors: Pontus K E Borjesson, Yvonne W S Jauw, Remco De Bree, J C Roos, Jonas A Castelijns, Rene C Leemans, Guus A M S Van Dongen, Ronald Boellaard
    Abstract:

    Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter 89Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans 89Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the 89Zr-labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. Methods: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of 89Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo Radioactivity Measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. Results:89Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% ± 16.9% [mean ± SD]) except for heavy-weight patients (>100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, −8.4% ± 34.5%). The mean absorbed red marrow dose was 0.07 ± 0.02 mSv/MBq and 0.09 ± 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 ± 0.27 mSv/MBq in men and 1.35 ± 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 ± 0.03 mSv/MBq in men and 0.66 ± 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. Conclusion:89Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAb-based therapy.

  • radiation dosimetry of 89zr labeled chimeric monoclonal antibody u36 as used for immuno pet in head and neck cancer patients
    The Journal of Nuclear Medicine, 2009
    Co-Authors: Pontus K E Borjesson, Yvonne W S Jauw, Remco De Bree, J C Roos, Jonas A Castelijns, Rene C Leemans, Guus A M S Van Dongen, Ronald Boellaard
    Abstract:

    UNLABELLED: Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter (89)Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans (89)Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the (89)Zr-labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. METHODS: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of (89)Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo Radioactivity Measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. RESULTS: (89)Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% +/- 16.9% [mean +/- SD]) except for heavy-weight patients (>100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, -8.4% +/- 34.5%). The mean absorbed red marrow dose was 0.07 +/- 0.02 mSv/MBq and 0.09 +/- 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 +/- 0.27 mSv/MBq in men and 1.35 +/- 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 +/- 0.03 mSv/MBq in men and 0.66 +/- 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. CONCLUSION: (89)Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAb-based therapy.

J F Garcia - One of the best experts on this subject based on the ideXlab platform.

  • crosslinked plastic scintillators a new detection system for Radioactivity Measurement in organic and aggressive media
    Analytica Chimica Acta, 2014
    Co-Authors: H Bagan, A Tarancon, J F Garcia
    Abstract:

    The Measurement of radioactive solutions containing organic or aggressive media may cause stability problems in liquid and plastic scintillation (PS) techniques. In the case of PS, this can be overcome by adding a crosslinker to the polymer structure. The objectives of this study are to synthesise a suitable crosslinked plastic scintillator (C-PS) for Radioactivity determination in organic and aggressive media. The results indicated that an increase in the crosslinker content reduces the detection efficiency and a more flexible crosslinker yields higher detection efficiency. For the polymer composition studied, 2,5-diphenyloxazole (PPO) is the most adequate fluorescent solute and an increase in its concentration causes little change in the detection efficiency. The inclusion of a secondary fluorescent solute 1,4-bis-2-(5-phenyloxazolyl) benzene (POPOP) improves the C-PS radiometrical characteristics. For the final composition chosen, the synthesis of the C-PS exhibits good reproducibility with elevated yield. The obtained C-PS also displays high stability in different organic (toluene, hydrotreated vegetable oil (HVO) and methanol) and aggressive media (hydrochloric acid, nitric acid and hydrogen peroxide). Finally, the C-PS exhibits high detection efficiency both in water and in aggressive media and can also be applied in organic media showing similar or even higher detection efficiency values.

  • crosslinked plastic scintillators a new detection system for Radioactivity Measurement in organic and aggressive media
    Analytica Chimica Acta, 2014
    Co-Authors: H Bagan, A Tarancon, Lei Ye, J F Garcia
    Abstract:

    The Measurement of radioactive solutions containing organic or aggressive media may cause stability problems in liquid and plastic scintillation (PS) techniques. In the case of PS, this can be overcome by adding a crosslinker to the polymer structure. The objectives of this study are to synthesise a suitable crosslinked plastic scintillator (C-PS) for Radioactivity determination in organic and aggressive media. The results indicated that an increase in the crosslinker content reduces the detection efficiency and a more flexible crosslinker yields higher detection efficiency. For the polymer composition studied, 2,5-diphenyloxazole (PPO) is the most adequate fluorescent solute and an increase in its concentration causes little change in the detection efficiency. The inclusion of a secondary fluorescent solute 1,4-bis-2-(5-phenyloxazolyl) benzene (POPOP) improves the C-PS radiometrical characteristics. For the final composition chosen, the synthesis of the C-PS exhibits good reproducibility with elevated yield. The obtained C-PS also displays high stability in different organic (toluene, hydrotreated vegetable oil (HVO) and methanol) and aggressive media (hydrochloric acid, nitric acid and hydrogen peroxide). Finally, the C-PS exhibits high detection efficiency both in water and in aggressive media and can also be applied in organic media showing similar or even higher detection efficiency values. (C) 2014 Elsevier B.V. All rights reserved.

Amarnath Challapalli - One of the best experts on this subject based on the ideXlab platform.

  • 18f icmt 11 a caspase 3 specific pet tracer for apoptosis biodistribution and radiation dosimetry
    The Journal of Nuclear Medicine, 2013
    Co-Authors: Amarnath Challapalli, Kasia Kozlowski, Laura M Kenny, William A Hallett, Giampaolo Tomasi, Mihir Gudi, Adil Alnahhas, Charles R Coombes, Eric O. Aboagye
    Abstract:

    Effective anticancer therapy induces tumor cell death through apoptosis. Noninvasive monitoring of apoptosis during therapy may provide predictive outcome information and help tailor treatment. A caspase-3–specific imaging radiotracer, 18F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin (18F-ICMT-11), has been developed for use in PET studies. We report the safety, biodistribution, and internal radiation dosimetry profiles of 18F-ICMT-11 in 8 healthy human volunteers. Methods:18F-ICMT-11 was intravenously administered as a bolus injection (mean ± SD, 159 ± 2.75 MBq; range, 154–161 MBq) to 8 healthy volunteers (4 men, 4 women). Whole-body (vertex to mid thigh) PET/CT scans were acquired at 6 time points, up to 4 h after tracer injection. Serial whole blood, plasma, and urine samples were collected for Radioactivity Measurement and radiotracer stability. In vivo 18F activities were determined from quantitative analysis of the images, and time–activity curves were generated. The total numbers of disintegrations in each organ normalized to injected activity (residence times) were calculated as the area under the curve of the time–activity curve, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using OLINDA/EXM 1.1. Results: Injection of 18F-ICMT-11 was well tolerated in all subjects, with no serious tracer-related adverse events reported. The mean effective dose averaged over both men and women was estimated to be 0.025 ± 0.004 mSv/MBq (men, 0.022 ± 0.004 mSv/MBq; women, 0.027 ± 0.004 mSv/MBq). The 5 organs receiving the highest absorbed dose (mGy/MBq), averaged over both men and women, were the gallbladder wall (0.59 ± 0.44), small intestine (0.12 ± 0.05), upper large intestinal wall (0.08 ± 0.07), urinary bladder wall (0.08 ± 0.02), and liver (0.07 ± 0.01). Elimination was both renal and via the hepatobiliary system. Conclusion:18F-ICMT-11 is a safe PET tracer with a dosimetry profile comparable to other common 18F PET tracers. These data support the further development of 18F-ICMT-11 for clinical imaging of apoptosis.

  • biodistribution and radiation dosimetry of 18f icmt 11 a caspase 3 specific pet tracer for apoptosis
    The Journal of Nuclear Medicine, 2013
    Co-Authors: Amarnath Challapalli, Kasia Kozlowski, Laura M Kenny, William A Hallett, Giampaolo Tomasi, Mihir Gudi, Adil Alnahhas, Charles Coombes, Eric O. Aboagye
    Abstract:

    161 Objectives 18F-ICMT-11, a caspase-3 specific apoptosis imaging radiotracer, has been developed for imaging by PET (1, 2). We present the first in human study of 18F-ICMT-11 that reports safety, biodistribution and internal radiation dosimetry profiles. Methods Whole body (vertex to mid-thigh) PET/CT scans of eight healthy volunteers were acquired at 6 time points, up to 4 h after 18F-ICMT-11 bolus injection (Mean±SD: 159 MBq ±2.75). Serial blood and urine samples were collected for Radioactivity Measurement. The images were quantitatively analyzed to determine in-vivo 18F activities and generate time activity curves (TACs). The total numbers of disintegrations in each organ (Residence Times: area under curve of the TAC normalized to injected activities and standard organ volumes) were calculated. Dosimetry calculations were performed using OLINDA/EXM 1.1. Results Injection of 18F-ICMT-11 was well tolerated, with no serious tracer related adverse events reported. Elimination was via the renal and hepatobiliary system. Assuming bladder voiding at 2-hrs, the 5 organs receiving the highest absorbed dose (mGy/MBq; ±SD), were the gall bladder wall (0.59±0.44), small intestine (0.12±0.05), upper large intestinal wall (0.08±0.07), urinary bladder wall (0.08±0.02), and liver (0.07±0.01). The mean effective dose and effective dose equivalent (±SD; mSv/MBq) were estimated to be 0.025±0.004 (male 0.022±0.004; female 0.027±0.004) and 0.067±0.022 (male 0.067±0.022; female 0.068±0.009), respectively. Conclusions 18F-ICMT-11 is safe, and has favorable radiation dosimetry profile for clinical imaging. This supports further evaluation of 18F-ICMT-11 to assess the magnitude of apoptosis in patients following cancer therapy.

Pontus K E Borjesson - One of the best experts on this subject based on the ideXlab platform.

  • radiation dosimetry of 89zr labeled chimeric monoclonal antibody u36 as used for immuno pet in head and neck cancer patients
    The Journal of Nuclear Medicine, 2009
    Co-Authors: Pontus K E Borjesson, Yvonne W S Jauw, Remco De Bree, J C Roos, Jonas A Castelijns, Rene C Leemans, Guus A M S Van Dongen, Ronald Boellaard
    Abstract:

    Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter 89Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans 89Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the 89Zr-labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. Methods: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of 89Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo Radioactivity Measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. Results:89Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% ± 16.9% [mean ± SD]) except for heavy-weight patients (>100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, −8.4% ± 34.5%). The mean absorbed red marrow dose was 0.07 ± 0.02 mSv/MBq and 0.09 ± 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 ± 0.27 mSv/MBq in men and 1.35 ± 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 ± 0.03 mSv/MBq in men and 0.66 ± 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. Conclusion:89Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAb-based therapy.

  • radiation dosimetry of 89zr labeled chimeric monoclonal antibody u36 as used for immuno pet in head and neck cancer patients
    The Journal of Nuclear Medicine, 2009
    Co-Authors: Pontus K E Borjesson, Yvonne W S Jauw, Remco De Bree, J C Roos, Jonas A Castelijns, Rene C Leemans, Guus A M S Van Dongen, Ronald Boellaard
    Abstract:

    UNLABELLED: Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter (89)Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans (89)Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the (89)Zr-labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. METHODS: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of (89)Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo Radioactivity Measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. RESULTS: (89)Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% +/- 16.9% [mean +/- SD]) except for heavy-weight patients (>100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, -8.4% +/- 34.5%). The mean absorbed red marrow dose was 0.07 +/- 0.02 mSv/MBq and 0.09 +/- 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 +/- 0.27 mSv/MBq in men and 1.35 +/- 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 +/- 0.03 mSv/MBq in men and 0.66 +/- 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. CONCLUSION: (89)Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAb-based therapy.