scholarly journals Effect of microdistribution of alpha and beta-emitters in targeted radionuclide therapies on delivered absorbed dose in a GATE model of bone marrow

2020 ◽  
Author(s):  
Jonathan Tranel ◽  
Felix Y Feng ◽  
Sara T St. James ◽  
Thomas A Hope
Keyword(s):  
Bone Marrow ◽  
Absorbed Dose ◽  
Beta Emitters

Dosimetry with 188Re-labelled monoclonal anti-CD66 antibodies

2006 ◽  
Vol 45 (03) ◽  
pp. 134-138 ◽  
Author(s):  
T. Kull ◽  
N. M. Blumstein ◽  
D. Bunjes ◽  
B. Neumaier ◽  
A. K. Buck ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Gamma Camera ◽  
Absorbed Dose ◽  
Correlation Coefficients ◽  
Residence Times ◽  
Reliable Prediction ◽  
Red Bone Marrow ◽  
Antibody Preparation ◽  
Simplified Method

SummaryAim: For the therapeutic application of radiopharmaceuticals the activity is determined on an individual basis. Here we investigated the accuracy for a simplified assessment of the residence times for a 188Re-labelled anti-CD66 monoclonal antibody. Patients, methods: For 49 patients with high risk leukaemia (24 men, 25 women, age: 44 ± 12 years) the residence times were determined for the injected 188Re-labelled anti-CD66 antibodies (1.3 ± 0.4 GBq, 5–7 GBq/mg protein, >95% 188Re bound to the antibody) based on 5 measurements (1.5, 3, 20, 26, and 44 h p.i.) using planar conjugate view gamma camera images (complete method). In a simplified method the residence times were calculated based on a single measurement 3 h p.i. Results: The residence times for kidneys, liver, red bone marrow, spleen and remainder of body for the complete method were 0.4 ± 0.2 h, 1.9 ± 0.8 h, 7.8 ± 2.1 h, 0.6 ± 0.3 h and 8.6 ± 2.1 h, respectively. For all organs a linear correlation exists between the residence times of the complete method and the simplified method with the slopes (correlation coefficients R > 0.89) of 0.89, 0.99, 1.23, 1.13 and 1.09 for kidneys, liver, red bone marrow, spleen and remainder of body, respectively. Conclusion: The proposed approach allows reliable prediction of biokinetics of 188Re-labelled anti-CD66 monoclonal antibody biodistribution with a single study. Efficient pretherapeutic estimation of organ absorbed dose may be possible, provided that a more stable anti-CD66 antibody preparation is available.

scholarly journals Targeted α particle immunotherapy for myeloid leukemia

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1233-1239 ◽  
Author(s):  
Joseph G. Jurcic ◽  
Steven M. Larson ◽  
George Sgouros ◽  
Michael R. McDevitt ◽  
Ronald D. Finn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Absorbed Dose ◽  
Myelogenous Leukemia ◽  
Whole Body ◽  
Hematopoietic Stem ◽  
Acute Myelogenous ◽  
Antigen System ◽  
High Doses ◽  
Nonspecific Cytotoxicity

Unlike β particle–emitting isotopes, α emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the β-emitters 131I and 90Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of β-emitting constructs, the α-emitting isotope 213Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg 213Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the 213Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with β-emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of 213Bi-HuM195, and it is the first proof-of-concept for systemic targeted α particle immunotherapy in humans.

The absorbed dose to bone marrow in the treatment of polycythaemla by32P

1976 ◽  
Vol 49 (578) ◽  
pp. 133-140 ◽  
Author(s):  
F. W. Spiers ◽  
A. H. Beddoe ◽  
S. D. King ◽  
C. J. Hayter ◽  
A. H. Smith ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Absorbed Dose

scholarly journals Calculation of absorbed dose due to the 90Y-DOTATOC peptide receptor radionuclide therapy by MCNP5/X

2018 ◽  
Vol 33 (4) ◽  
pp. 380-385
Author(s):  
Marija Jeremic ◽  
Milovan Matovic ◽  
Suzana Pantovic ◽  
Dragoslav Nikezic ◽  
Dragana Krstic
Keyword(s):  
Radionuclide Therapy ◽  
Somatostatin Receptors ◽  
Computer Software ◽  
Absorbed Dose ◽  
Peptide Receptor Radionuclide Therapy ◽  
Beta Radiation ◽  
Bremsstrahlung Radiation ◽  
Peptide Receptor ◽  
Beta Emitters ◽  
Good Expression

Strong beta emitters, like 90Y, 177Lu labelled peptide, are used for treatment of neuroendocrine tumours where there is a good expression of somatostatin receptors. In this work, MCNP5/X computer software and ORNL human phantoms were used to calculate absorbed dose due to 90Y labelled DOTATOC in the peptide receptor radionuclide therapy. Tumour was considered as a sources of beta radiation and represented as a sphere with diameter of 1-4 cm and 5 cm in liver, pancreas, and lungs. Results are expressed as absorbed dose per unit of cumulated activity, S ? value in units mGy?(MBq?s)?1. The far largest dose is in tumour itself, then in organ which contains the tumour. Doses in other organs, where the metastasis are the most frequent, due to the bremsstrahlung radiation, are much smaller and could be neglected. The largest dose, 8.66?10?3 mGy?(MBq?s)?1 was obtained for tumour with size of 3 cm.

scholarly journals 52Fe for additional marrow ablation before bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3435-3439 ◽  
Author(s):  
A Ferrant ◽  
M Cogneau ◽  
N Leners ◽  
F Jamar ◽  
P Martiat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Whole Body ◽  
Median Percentage ◽  
Preparative Regimen

Abstract The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.

scholarly journals Radiolabeled anti-CD45 monoclonal antibodies target lymphohematopoietic tissue in the macaque

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1864-1874 ◽  
Author(s):  
DC Matthews ◽  
FR Appelbaum ◽  
JF Eary ◽  
TE Hui ◽  
DR Fisher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Lymph Nodes ◽  
Marrow Transplantation ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Macaca Nemestrina ◽  
Improve Treatment ◽  
Antibody Uptake ◽  
Relative Specificity

Abstract Despite bone marrow transplantation, many patients with advanced leukemia subsequently relapse. If an additional increment of radiation could be delivered to lymphohematopoietic tissues with relative specificity, the relapse rate may decrease without a marked increase in toxicity. We have examined the biodistribution of two 131I-labeled monoclonal antibodies reactive with the CD45 antigen in Macaca nemestrina. Three animals received 0.5 mg/kg BC8, an IgG1 of low avidity (6 x 10(7) L/mol). Three received 0.5 mg/kg AC8, an IgG2a of moderate avidity (5 x 10(8) L/mol), and two received 4.5 mg/kg AC8. Estimates of radiation absorbed dose demonstrated that these antibodies could deliver up to five times more radiation to lymph nodes, and up to 2.6 times more to bone marrow, than to lung or liver. The higher avidity AC8 antibody at 0.5 mg/kg was cleared more rapidly from blood and resulted in lower antibody uptake in lymph nodes than did BC8 at 0.5 mg/kg. Increasing the dose of AC8 to 4.5 mg/kg resulted in slower blood clearance and higher lymph node uptake. These studies suggest that radiolabeled anti-CD45 antibodies can deliver radiation with relative specificity to lymphohematopoietic tissues. This approach, in combination with marrow transplantation, may improve treatment of hematologic malignancies.

scholarly journals Dosimetry of Bone-Seeking Radiopharmaceuticals for Palliative Therapy of Bone Metastases: A Simulation Study Using GATE Monte Carlo Code

2020 ◽  
Author(s):  
Saman Dalvand ◽  
Hossein Rajabi ◽  
Ameneh Omidi ◽  
Etesam Malekzadeh
Keyword(s):  
Bone Marrow ◽  
Monte Carlo ◽  
Bone Metastases ◽  
Bone Structure ◽  
Palliative Therapy ◽  
Absorbed Dose ◽  
Monte Carlo Code ◽  
Pain Palliation ◽  
Beta Particles ◽  
Absorbed Doses

Purpose: Radiopharmaceutical Therapy (RPT) is one of the effective methods for pain palliation of bone metastases. Bone marrow is a critical organ in bone structure whose absorbed dose should be kept below a certain threshold. The purpose of this study was to calculate and compare absorbed doses of bone-seeking radiopharmaceuticals used in the palliative treatment of bone metastases. Materials and Methods: In this study, the GATE Monte Carlo code was used to simulate a femur bone, which consists of bone marrow, endosteal layer, bone, and soft tissue phantom model. Absorbed doses of the 153Sm-EDTMP, 89SrCl2, 177Lu-EDTMP, 188Re-HEDP, and 223RaCl2 radiopharmaceuticals were calculated in the femur phantom compartments. Results: bone absorbed doses per disintegration from alpha particles of 223RaCl2 is approximately 24 times higher than absorbed doses from beta particles of 89SrCl2. Also, absorbed dose per disintegration from beta particles of 89SrCl2 in the bone is approximately 12, 6 and 1.5 times higher than 177Lu-EDTMP, 153Sm-EDTMP, and 188Re-HEDP, respectively. Moreover, the bone and bone marrow absorbed dose from beta particles of 153Sm-EDTMP is 1.9 times higher than 177Lu-EDTMP. Besides, absorbed dose per disintegration from beta particles of 188Re-HEDP in the bone marrow is approximately 40, 30, 7, and 4 times higher than 223RaCl2, 89SrCl2, 177Lu-EDTMP and 153Sm-EDTMP, respectively. Conclusion: Our results show that 223RaCl2 could be a more efficient radiopharmaceutical for radionuclide therapy of bone metastases. Also, 177Lu-EDTMP, due to low marrow toxicity and comparable bone absorbed dose with 153Sm-EDTMP, can be used for achieving bone pain palliation. Moreover, significantly high bone marrow absorbed dose of 188Re-HEDP should be considered for palliative therapy of metastatic bone patients.

scholarly journals Simple model for estimation of absorbed dose by organs and tumors after PRRT from a single SPECT/CT study

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Alexandre Chicheportiche ◽  
Moshe Sason ◽  
Jeremy Godefroy ◽  
Yodphat Krausz ◽  
Mahmoud Zidan ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Marrow ◽  
Activity Concentration ◽  
Absorbed Dose ◽  
The Body ◽  
Emission Computed Tomography ◽  
Standard Protocol ◽  
Independent Variables ◽  
Absorbed Doses ◽  
Mlr Model

Abstract Background Following each cycle of peptide receptor radionuclide therapy (PRRT), absorbed doses by tumors and normal organs are typically calculated from three quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT) studies acquired at t1 = 24 h, t2 = 96 h, t3 = 168 h after the first cycle of treatment and from a single study at t1 after the subsequent cycles. In the present study, we have assessed the feasibility of a single SPECT/CT study after each PRRT cycle using a trained multiple linear regression (MLR) model for absorbed dose calculation and have evaluated its impact on patient management. Quantitative [177Lu]-DOTA-TATE SPECT/CT data after PRRT of seventy-two consecutive metastatic neuroendocrine tumors patients were retrospectively evaluated. A set of 40 consecutive studies was used to train the MLR model. The two independent variables of the model included the time of imaging after administration of the treatment and the radiopharmaceutical activity concentration in a given  organ/tumor. The dependent variable was the dose absorbed by the organ/tumor obtained with the standard protocol. For bone marrow dosimetry, the independent variables included the time of imaging, and the blood and remainder of the body activity concentration. The model was evaluated in 32 consecutive patients. Absorbed doses were assessed for kidneys, bone marrow, liver, spleen and tumor sites. Results There was no difference in management decisions, whether PRRT can be safely continued or not because unsafe absorbed dose to risk organs between the standard and the MLR model-based protocol using a single SPECT/CT study performed at t3 = 168 h after the first cycle and at t1 = 24 h after the subsequent cycles. Cumulative absorbed doses were obtained with mean relative differences of − 0.5% ± 5.4%, 1.6% ± 15.1%, − 6.2% ± 7.3%, − 5.5% ± 5.8% and 2.9% ± 12.7% for kidneys, bone marrow, liver, spleen and tumors, respectively (Pearson’s r correlation coefficient 0.99, 0.91, 0.99, 0.99 and 0.97, respectively). Conclusion Dosimetry calculations using a MLR model with a single SPECT/CT study are in good agreement with the standard protocol, while avoiding the use of dosimetry software and enabling improved patient comfort and reduced scanner and staff time.

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