scholarly journals Evaluation of the 223Ra-dichloride biodistribution models for the assessment of the doses from internal exposure

2020 ◽  
Vol 2 (1) ◽  
pp. 54-69
Author(s):  
Aleksandr V. Vodovatov ◽  
Larisa A. Chipiga ◽  
Anna E. Petrova ◽  
Andrey A. Stanzhevsky
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Bone Metastases ◽  
Absorbed Dose ◽  
The Body ◽  
Internal Exposure ◽  
Bone Surface ◽  
Red Bone Marrow ◽  
Absorbed Doses ◽  
Healthy Part

Prostate cancer is the most common men urogenital tumor. For most patients with the disseminated neoplastic process in the prostate after the hormonal therapy, the disease gradually progresses in the form of castration-resistant prostate cancer (mCRPC). The use of 223Ra agents is aimed at the treatment of the bone lesions as part of palliative therapy. The physical properties of 223Ra significantly complicate the require direct radiometry for patients with alpha emitters. Hence, the distribution of 223Ra in the body should be evaluated based on the dedicated biodistribution models. The aim of this study was to review and analyze the existing approaches to the evaluation of the biodistribution of 223Ra and its pharmaceutical forms (223Ra-dichloride) for the further assessment of absorbed doses in radiosensitive organs and tissues. The study includes the mathematical models for the estimation of the absorbed doses in various organs and tissues of the body. A review of three different 223Ra biodistribution models is presented: two ICRP models for occupational exposure and a model based on the results of an experimental assessment of 223Ra distribution in patients with mCRPC. It was indicated that the latter model is in good agreement with the results of direct radiometry of patients. A significant drawback of all models is the simulation of the red bone marrow and bone surface as single chambers. During the radionuclide therapy, 223Ra will specifically accumulate in bone metastases, instead of being evenly distributed in the skeleton. Hence, the use of any of the reviewed models will lead both to a significant overestimation of the absorbed dose in a healthy part of the bone surface and red bone marrow, and to an underestimation of the absorbed dose in bone metastases. Currently, this problem has not been solved. That requires the development of new improved models that consider the accumulation of 223Ra in the healthy part of the skeleton and in skeletal metastases.

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.

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 α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients

2021 ◽  
Author(s):  
S. Schumann ◽  
U. Eberlein ◽  
C. Lapa ◽  
J. Müller ◽  
S. Serfling ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cancer Patients ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Absorbed Dose ◽  
Peripheral Blood Mononuclear ◽  
Absorbed Doses ◽  
Blood Mononuclear Cells

Abstract Purpose One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. Methods Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. Results The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h – 4 weeks after administration), the α-track frequency remained elevated. Conclusion The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.

Metastatic disease in prostate cancer

2017 ◽  
Author(s):  
Noel W Clarke
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Metastatic Disease ◽  
Primary Site ◽  
Red Bone Marrow ◽  
Cellular Survival ◽  
Local Tissue ◽  
Lymphatic Circulation ◽  
Aggressive Form ◽  
Indolent Disease

Metastases are the predominant cause of morbidity and death from prostate cancer (CaP). The tendency for cells to migrate from the primary site, enter the vascular/lymphatic circulation, and implant/grow at secondary sites is the principal discriminator of aggressive form indolent disease. But this process is poorly understood. Cells enter the circulation in increasing number as the disease progresses, impinging on endothelial surfaces, particularly in red bone marrow where they bind and transmigrate, forming early cell colonies. This requires chemo-attractants and nutrients enabling cellular survival. Established metastases thrive independently, disrupting local tissue, as characterized by progressive replacement of red bone marrow and disruption of skeletal architecture. Bone disruption includes massive overstimulation of both osteoblasts and osteoclasts, inducing synchronous over-production of abnormal bone and gross osteolysis.

scholarly journals BLOOD CELL FORMATION AND DISTRIBUTION IN RELATION TO THE MECHANISM OF THYROID-ACCELERATED METAMORPHOSIS IN THE LARVAL FROG

1923 ◽  
Vol 38 (5) ◽  
pp. 529-541 ◽  
Author(s):  
H. E. Jordan ◽  
C. C. Speidel
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Metabolic Rate ◽  
Cell Formation ◽  
The Body ◽  
Red Bone Marrow ◽  
History Of ◽  
Regressive Change ◽  
Mesenchymal Precursor ◽  
Hemopoietic Organ

1. Thyroid-accelerated metamorphosis in the larval frog is accompanied by changes in the hemopoietic centers and in the blood cell distribution in the various regions of the body. These changes are interpreted as results of the fundamental change in basal metabolic rate induced by the thyroid treatment. 2. There is initiation of the shift of hemopoietic locus from the kidney, the larval hemopoietic organ, to the spleen, the adult hemopoietic organ. The spleen, being chiefly an erythrocyte producer, becomes of greater importance with the transition from the lower metabolic rate to the higher, since greater erythropoiesis becomes necessary to supply the physical basis for the maintenance of the higher metabolic rate. 3. It is suggested that the appearance of red bone marrow in the later history of the frog is correlated with a still higher metabolic rate. Phylogenetically, in the vertebrate series, red bone marrow is also associated with higher metabolic rate. 4. The new metabolic rate initiated in tadpoles by thyroid administration sets up a demand for (a) erythrocytes, (b) granulocytes and lymphoid phagocytes for distribution to regions of regressive change, (c) lymphocytes, (1) as progenitors of erythrocytes, granulocytes and phagocytes, (2) for promoting growth of cells in regions of progressive change. 5. Upon the hemopoietic reserve, which in the last analysis is the lymphocyte (and its mesenchymal precursor), depends the extent to which metamorphosis will proceed. Inability on the part of the hemopoietic centers, chiefly the spleen, to keep pace with the demand for blood cells during metamorphosis results in metamorphic stasis, a condition of anemia which is usually followed by death. 6. The growth-promoting function of leucocytes, as demonstrated by Carrel, is probably to be ascribed to the lymphocyte component of leucocytes. 7. The granulocytes have probably also a glandular function, and may exert a lytic effect upon adjacent tissues in regions of regressive change.

X.—Mitosis and Cell Differentiation in the Blood

1944 ◽  
Vol 62 (1) ◽  
pp. 73-85 ◽  
Author(s):  
L. F. La Cour
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
The Body ◽  
Red Bone Marrow ◽  
Original Type

It was in 1878 that Ehrlich, with the aid of his triacid stain, described in terms of granulation of the cytoplasm six types of leucocytes. This marked the first real advance in our knowledge of the blood corpuscles. Present-day classification of cells in the blood-forming tissues gives six main groups with about thirty named types of cells. These fine subdivisions appear to represent different stages in different lines of development from one original type, chiefly by change in the shape of the resting nucleus. Divergence in opinion arises as to whether all these types of cell develop in the red bone marrow, or whether some arise elsewhere in the body.

608 Bone marrow magnetic resonance imaging allows objective assessment of prostate cancer (PCA) bone metastases

2004 ◽  
Vol 3 (2) ◽  
pp. 154
Author(s):  
B. Tombal ◽  
G. Van Heugen ◽  
A. Rezazadeh ◽  
P. Van Cangh ◽  
B. Vande Berg ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Prostate Cancer ◽  
Bone Marrow ◽  
Magnetic Resonance ◽  
Bone Metastases ◽  
Objective Assessment ◽  
Resonance Imaging

Colloid Scintigraphy Showing Red Bone Marrow Extension in Patients with Prostatic Carcinoma

1992 ◽  
Vol 33 (2) ◽  
pp. 97-102 ◽  
Author(s):  
U. Rudberg ◽  
R. Udén ◽  
S.-O. Ahlbäck
Keyword(s):  
At Risk ◽  
Bone Marrow ◽  
Bone Metastases ◽  
Prostatic Carcinoma ◽  
Lower Extremities ◽  
Reticuloendothelial System ◽  
Red Bone Marrow ◽  
Fracture Bone

In 25 of 30 patients with bone metastases from prostatic carcinoma, red bone marrow extension was observed by scintigraphy of the reticuloendothelial system (RES). The degree of bone marrow extension in the lower extremities increased with increasing number of bone metastases. In 8 patients, 15 peripheral metastases were detected, all located in areas with extended red bone marrow. The distal level of bone marrow extension coincided with that of the most distal metastases. This is of importance for the detection of peripheral metastases at risk for fracture. Bone marrow extension was also seen in 5 of 8 patients with prostatic carcinoma without bone metastases and was interpreted as a paramalignant activation of RES.

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