Dosimetry and Therapeutic Ratios for Rhenium-186 HEDP

Rhenium-186 (Re-186) is a β-emitting radionuclide. Emitted β-particles have ranges up to 4.5 mm in tissue, capable of delivering high doses to skeletal regions of high Re-186 concentrations while sparing adjacent radiosensitive regions and thus making the irradiation well tolerated for the patient. Along with the β-emissions, γ-rays are emitted having an adequate energy for imaging during therapy and biodistribution assessment for patient-specific dosimetry calculations. The relatively short physical half-life combined with the β-emissions allows the delivery of relatively high activity rate for a short period of time in areas of concentration. This study is a short review concerning the palliative treatment of skeletal metastases using 186Re-HEDP. After presenting the dominant ways of 186Re production, special emphasis is given to dosimetry issues while the effect of palliation therapy can be evaluated through the comparison of the absorbed dose in metastatic lesion relatively to the normal bone region. Accurate dose estimation is required taking into account the anatomic individual difference of each patient. For this purpose a patient specific dosimetric model considering metastatic lesions as spherical nodules is introduced. In order to quantify in a representative way the results of palliation treatment, the concept of therapeutic ratios is analyzed.

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Contrast-Enhanced MRI with Magnetization Transfer Effect in the Imaging of Brain Metastatic Lesions

Medical Visualization ◽

10.24835/1607-0763-2017-5-8-17 ◽

2017 ◽

pp. 8-17

Author(s):

A. A. Ermakova ◽

O. Yu. Borodin ◽

M. Yu. Sannikov ◽

S. D. Koval ◽

V. Yu. Usov

Keyword(s):

Comparative Analysis ◽

Roc Analysis ◽

Magnetization Transfer ◽

Metastatic Lesion ◽

Transfer Effect ◽

Wilcoxon Test ◽

Post Contrast ◽

Metastatic Lesions ◽

The Brain ◽

Non Parametric

Purpose: to investigate the diagnostic opportunities of contrast magnetic resonance imaging with the effect of magnetization transfer effect in the diagnosis of focal metastatic lesions in the brain.Materials and methods.Images of contrast MRI of the brain of 16 patients (mean age 49 ± 18.5 years) were analysed. Diagnosis of the direction is focal brain lesion. All MRI studies were carried out using the Toshiba Titan Octave with magnetic field of 1.5 T. The contrast agent is “Magnevist” at concentration of 0.2 ml/kg was used. After contrasting process two T1-weighted studies were performed: without T1-SE magnetization transfer with parameters of pulse: TR = 540 ms, TE = 12 ms, DFOV = 24 sm, MX = 320 × 224 and with magnetization transfer – T1-SE-MTC with parameters of pulse: ΔF = −210 Hz, FA(МТС) = 600°, TR = 700 ms, TE = 10 ms, DFOV = 23.9 sm, MX = 320 x 224. For each detected metastatic lesion, a contrast-to-brain ratio (CBR) was calculated. Comparative analysis of CBR values was carried out using a non-parametric Wilcoxon test at a significance level p < 0.05. To evaluate the sensitivity and specificity of the techniques in the detection of metastatic foci (T1-SE and T1-SE-MTC), ROC analysis was used. The sample is divided into groups: 1 group is foci ≤5 mm in size, 2 group is foci from 6 to 10 mm, and 3 group is foci >10 mm. Results.Comparative analysis of CBR using non-parametric Wilcoxon test showed that the values of the CBR on T1-weighted images with magnetization transfer are significantly higher (p <0.001) that on T1-weighted images without magnetization transfer. According to the results of the ROC analysis, sensitivity in detecting metastases (n = 90) in the brain on T1-SE-MTC and T1-SE was 91.7% and 81.6%, specificity was 100% and 97.6%, respectively. The accuracy of the T1-SE-MTC is 10% higher in comparison with the technique without magnetization transfer. Significant differences (p < 0.01) between the size of the foci detected in post-contrast T1- weighted images with magnetization transfer and in post-contrast T1-weighted images without magnetization transfer, in particular for foci ≤5 mm in size, were found. Conclusions1. Comparative analysis of CBR showed significant (p < 0.001) increase of contrast between metastatic lesion and white matter on T1-SE-MTC in comparison with T1-SE.2. The sensitivity, specificity and accuracy of the magnetization transfer program (T1-SE-MTC) in detecting foci of metastatic lesions in the brain is significantly higher (p < 0.01), relative to T1-SE.3. The T1-SE-MTC program allows detecting more foci in comparison with T1-SE, in particular foci of ≤5 mm (96% and 86%, respectively, with p < 0.05).

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METASTATIC LESION OF THE SPINE: DIAGNOSIS AND TACTICS OF SURGICAL TREATMENT

Problems in oncology ◽

10.37469/0507-3758-2019-65-6-868-876 ◽

2019 ◽

Vol 65 (6) ◽

pp. 868-876

Author(s):

Anton Yarikov ◽

Anton Yermolaev ◽

Igor Smirnov ◽

Anton Denisov ◽

Olga Perlmutter ◽

...

Keyword(s):

Malignant Tumors ◽

Epidemiological Studies ◽

Metastatic Lesion ◽

Spinal Cord Damage ◽

Metastatic Lesions ◽

Spinal Lesions ◽

Cancer Pathology ◽

Surgical Methods ◽

The Stability ◽

Methods Of Treatment

Epidemiological studies show an increase in the number of people with cancer. Bone metastases are a frequent manifestation of generalized cancer, because it is in malignant tumors of the spine more often than other bones of the skeleton becomes a target for metastasis. The article describes in detail the methods of diagnosis of spinal lesions in cancer pathology. Particular attention is paid to the scales reflecting the severity of the patient’s condition, the degree of spinal cord damage, the severity of pain in metastasis to the spine, the prognosis of survival in oncovertebrology and evaluation of the stability of the spine in metastatic lesions. Further, the paper presents non-radical (decompression, vertebroplasty) and radical (spondylectomy, corporectomy) surgical methods of treatment

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Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice

Scientific Reports ◽

10.1038/s41598-021-94684-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Su Bin Kim ◽

In Ho Song ◽

Yoo Sung Song ◽

Byung Chul Lee ◽

Arun Gupta ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Dosimetry ◽

Xenograft Model ◽

Absorbed Dose ◽

Patient Specific ◽

Internal Radiation ◽

Washout Phase ◽

Heterogeneous Tissue ◽

Organ Level ◽

Reported Data

Abstract[68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [68Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [68Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [68Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions.

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Human Absorbed Dose Evaluation of [177Lu]Lu-IBA as a Bone Palliative Candidate

Nuklearmedizin ◽

10.1055/a-1486-3683 ◽

2021 ◽

Author(s):

Hassan Ranjbar ◽

Zahra Pourhabib

Keyword(s):

Radiochemical Purity ◽

Palliative Therapy ◽

Absorbed Dose ◽

Skeletal Metastases ◽

Clinical Pharmacokinetics ◽

Thermal Neutron Irradiation ◽

Biodistribution Data ◽

Biological Studies ◽

Significant Uptake

AbstractThe role of lutetium-177 among bone-seeking radionuclides in targeted therapy is noteworthy. The clinical pharmacokinetics of ibandronate (IBA) indicates that this bisphonate has powerful bone mineral affinity. The aim of this study was to evaluate of [177Lu]Lu-IBA efficacy as a new compound.The [177Lu]Lu-IBA was prepared by radiolabeling of IBA ligand to 177LuCl3 that was obtained by thermal neutron irradiation of enriched Lu2O3 sample. Produced [177Lu]Lu-IBA with high radiochemical purity was administered intravenously to mice. Biodistribution data were collected at 1, 4, 24, 48 h and 7 d post injections. With calculating accumulated activities in each organ and extrapolating mouse’s organs to human’s organs by the RADAR method and using OLINDA/EXM software the injected dose in various human organs was achieved.[177Lu]Lu-IBA was produced with radiochemical purity nearly 96 %. Its biodistribution data showed the high uptake and durability in the skeletal tissues without significant uptake in other major organs.The results showed that [177Lu]Lu-IBA has considerably good properties as a bone-seeking radiopharmaceutical and therefore can be a candidate for bone pain palliative therapy in skeletal metastases; however, further biological studies are still needed.

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Complex urbarchitectonic structures of Pristina and Novi Pazar cities

Spatium ◽

10.2298/spat1432039b ◽

2014 ◽

pp. 39-46 ◽

Cited By ~ 1

Author(s):

Dzemila Beganovic

Keyword(s):

Urban Development ◽

20Th Century ◽

Short Review ◽

Urban Transformation ◽

Urban Structures ◽

Short Period ◽

The World ◽

New Models ◽

Urban Organization ◽

Modern Movement

Contemporary urban development has changed the traditional cities all over the world. In our region, the typical Balkan cities of oriental origin, structure and outlook were almost totally transformed in the second half of the 20th century. Modern movement brought new models of urban organization, different communication concepts and a variety of concepts of modern buildings. Among others, the idea of complex urbarchitectonic structures in urban tissue spread under specific influences and models. After a short review of modern urban development and the idea of complex urban structures, this paper explores urban transformation of less researched cities such as Pristina and Novi Pazar. The focus is on the phenomenon of complex urbarchitectonic structures built in related cities in a short period from 1969-1989. Four complex urbarchitectonic structures will be presented: Kicma and complex in JNA Street in Pristina and Lucne buildings and Jezero buildings in Novi Pazar.

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Clinical Effectiveness of the Queen Square Intensive Comprehensive Aphasia Service for Patients With Poststroke Aphasia

Stroke ◽

10.1161/strokeaha.120.033837 ◽

2021 ◽

Author(s):

Alexander P. Leff ◽

Sarah Nightingale ◽

Beth Gooding ◽

Jean Rutter ◽

Nicola Craven ◽

...

Keyword(s):

Repeated Measures ◽

Clinical Effectiveness ◽

Functional Communication ◽

Auditory Comprehension ◽

Language Therapy ◽

Time Interaction ◽

Short Period ◽

High Doses ◽

Effectiveness Index ◽

Communicative Effectiveness

Background and Purpose: Poststroke aphasia has a major impact on peoples’ quality of life. Speech and language therapy interventions work, especially in high doses, but these doses are rarely achieved outside of research studies. Intensive Comprehensive Aphasia Programs (ICAPs) are an option to deliver high doses of therapy to people with aphasia over a short period of time. Methods: Forty-six people with aphasia in the chronic stage poststroke completed the ICAP over a 3-week period, attending for 15 days and averaging 6 hours of therapy per day. Outcome measures included the Comprehensive Aphasia Test, an impairment-based test of the 4 main domains of language (speaking, writing, auditory comprehension, and reading) which was measured at 3 time points (baseline, immediately posttreatment at 3 weeks and follow-up at 12-week post-ICAP); and, the Communicative Effectiveness Index, a carer-reported measure of functional communication skills collected at baseline and 12 weeks. Results: A 2-way repeated measures multivariate ANOVA was conducted. We found a significant domain-by-time interaction, F =12.7, P <0.0005, indicating that the ICAP improved people with aphasia’s language scores across all 4 domains, with the largest gains in speaking (Cohen’s d =1.3). All gains were maintained or significantly improved further at 12-week post-ICAP. Importantly, patients’ functional communication, as indexed by changes on the Communicative Effectiveness Index, also significantly improved at 12-week post-ICAP, t =5.4, P <0.0005, also with a large effect size (Cohen’s d =0.9). Conclusions: People with aphasia who participated in the Queen Square ICAP made large and clinically meaningful gains on both impairment-based and functional measures of language. Gains were sustained and in some cases improved further over the subsequent 12 weeks.

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Targeted α particle immunotherapy for myeloid leukemia

Blood ◽

10.1182/blood.v100.4.1233.h81602001233_1233_1239 ◽

2002 ◽

Vol 100 (4) ◽

pp. 1233-1239 ◽

Cited By ~ 305

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.

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