scholarly journals 177Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu: Biokinetics, Dosimetry, and Evaluation in Patients with Advanced Prostate Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Clara Santos-Cuevas ◽  
Guillermina Ferro-Flores ◽  
Francisco O. García-Pérez ◽  
Nallely Jiménez-Mancilla ◽  
Gerardo Ramírez-Nava ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Healthy Subjects ◽  
Slow Component ◽  
Optimal Number ◽  
Molecular Probe ◽  
Whole Body ◽  
Body Images ◽  
Time Activity ◽  
Biokinetic Model ◽  
Before And After

SPECT/CT images in patients have demonstrated the ability of [99mTc]Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ([99mTc]Tc-iPSMA) to detect tumors and metastases of prostate cancer. Considering that theranostics combines the potential of therapeutic and diagnostic radionuclides in the same molecular probe, the aim of this research was to estimate the biokinetics and dosimetry of 177Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu (177Lu-iPSMA) in healthy subjects and analyze the response in patients receiving 177Lu-iPSMA therapeutic doses. 177Lu-iPSMA was obtained from lyophilized formulations with radiochemical purities >98%. Whole-body images from five healthy subjects were acquired at 20 min, 6, 24, 48, and 120 h after 177Lu-iPSMA administration (185 MBq). The image sequence was used to extrapolate the 177Lu-iPSMA time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation doses. Ten patients (median age: 68 y; range 58–86 y) received from 1 to 4 cycles of 177Lu-iPSMA (3.7 or 7.4 GBq) every 8–10 weeks. Response was evaluated using the 68Ga-PSMA-ligand-PET/CT or 99mTc-iPSMA-SPECT/CT diagnostic images and serum PSA levels before and after 177Lu-iPSMA treatment. The blood activity showed a half-life value of 1.1 h for the fast component (T1/2α = ln2/0.614), 9.2 h for the first slow component (T1/2β = ln2/0.075), and 79.6 h for the second slow component (T1/2γ = ln2/0.008). The average absorbed doses were 0.23, 0.28, 0.88, and 1.17 Gy/GBq for the spleen, liver, kidney, and salivary glands. A total of 18 cycles were performed in 10 patients. A PSA decrease and some reduction of the radiotracer uptake (SUV) in tumor lesions occurred in 60% and 70% of the patients, respectively. 177Lu-iPSMA obtained from kit formulations showed high tumor uptake with good response rates in patients. The results obtained in this study warrant further clinical studies to establish the optimal number of treatment cycles and for evaluating the effect of this therapeutic agent on survival of patients.

scholarly journals Radiopharmacokinetic modelling and radiation dose assessment of 223Ra used for treatment of metastatic castration-resistant prostate cancer

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Vera Höllriegl ◽  
Nina Petoussi-Henss ◽  
Kerstin Hürkamp ◽  
Juan Camilo Ocampo Ramos ◽  
Wei Bo Li
Keyword(s):  
Prostate Cancer ◽  
Radiological Protection ◽  
Bolus Administration ◽  
Time Activity ◽  
Biokinetic Model ◽  
Castration Resistant ◽  
Absorbed Doses ◽  
Red Marrow ◽  
Dose Coefficients ◽  
Modelling Study

Abstract Purpose Ra-223 dichloride (223Ra, Xofigo®) is used for treatment of patients suffering from castration-resistant metastatic prostate cancer. The objective of this work was to apply the most recent biokinetic model for radium and its progeny to show their radiopharmacokinetic behaviour. Organ absorbed doses after intravenous injection of 223Ra were estimated and compared to clinical data and data of an earlier modelling study. Methods The most recent systemic biokinetic model of 223Ra and its progeny, developed by the International Commission on Radiological Protection (ICRP), as well as the ICRP human alimentary tract model were applied for the radiopharmacokinetic modelling of Xofigo® biodistribution in patients after bolus administration. Independent kinetics were assumed for the progeny of 223Ra. The time activity curves for 223Ra were modelled and the time integrated activity coefficients, $$ \overset{\sim }{a}\left({r}_S,{T}_D\right), $$ a ~ r S T D , in the source regions for each progeny were determined. For estimating the organ absorbed doses, the Specific Absorbed Fractions (SAF) and dosimetric framework of ICRP were used together with the aforementioned $$ \overset{\sim }{a}\left({r}_S,{T}_D\right) $$ a ~ r S T D values. Results The distribution of 223Ra after injection showed a rapid plasma clearance and a low urinary excretion. Main elimination was via faeces. Bone retention was found to be about 30% at 4 h post-injection. Similar tendencies were observed in clinical trials of other authors. The highest absorbed dose coefficients were found for bone endosteum, liver and red marrow, followed by kidneys and colon. Conclusion The biokinetic modelling of 223Ra and its progeny may help to predict their distributions in patients after administration of Xofigo®. The organ dose coefficients of this work showed some variation to the values reported from clinical studies and an earlier compartmental modelling study. The dose to the bone endosteum was found to be lower by a factor of ca. 3 than previously estimated.

Influence of endurance training on muscle [PCr] kinetics during high-intensity exercise

2007 ◽  
Vol 293 (1) ◽  
pp. R392-R401 ◽  
Author(s):  
Andrew M. Jones ◽  
Daryl P. Wilkerson ◽  
Nicolas J. Berger ◽  
Jonathan Fulford
Keyword(s):  
Endurance Training ◽  
High Intensity ◽  
Slow Component ◽  
Knee Extension ◽  
High Intensity Exercise ◽  
Whole Body ◽  
Time To Exhaustion ◽  
Exercise Tests ◽  
Before And After ◽  
Knee Extension Exercise

We hypothesized that a period of endurance training would result in a speeding of muscle phosphocreatine concentration ([PCr]) kinetics over the fundamental phase of the response and a reduction in the amplitude of the [PCr] slow component during high-intensity exercise. Six male subjects (age 26 ± 5 yr) completed 5 wk of single-legged knee-extension exercise training with the alternate leg serving as a control. Before and after the intervention period, the subjects completed incremental and high-intensity step exercise tests of 6-min duration with both legs separately inside the bore of a whole-body magnetic resonance spectrometer. The time-to-exhaustion during incremental exercise was not changed in the control leg [preintervention group (PRE): 19.4 ± 2.3 min vs. postintervention group (POST): 19.4 ± 1.9 min] but was significantly increased in the trained leg (PRE: 19.6 ± 1.6 min vs. POST: 22.0 ± 2.2 min; P < 0.05). During step exercise, there were no significant changes in the control leg, but end-exercise pH and [PCr] were higher after vs. before training. The time constant for the [PCr] kinetics over the fundamental exponential region of the response was not significantly altered in either the control leg (PRE: 40 ± 13 s vs. POST: 43 ± 10 s) or the trained leg (PRE: 38 ± 8 s vs. POST: 40 ± 12 s). However, the amplitude of the [PCr] slow component was significantly reduced in the trained leg (PRE: 15 ± 7 vs. POST: 7 ± 7% change in [PCr]; P < 0.05) with there being no change in the control leg (PRE: 13 ± 8 vs. POST: 12 ± 10% change in [PCr]). The attenuation of the [PCr] slow component might be mechanistically linked with enhanced exercise tolerance following endurance training.

scholarly journals Bone metastasis classification using whole body images from prostate cancer patients based on convolutional neural networks application

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0237213 ◽  
Author(s):  
Nikolaos Papandrianos ◽  
Elpiniki Papageorgiou ◽  
Athanasios Anagnostis ◽  
Konstantinos Papageorgiou
Keyword(s):  
Prostate Cancer ◽  
Neural Networks ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Convolutional Neural Networks ◽  
Whole Body ◽  
Body Images

Outcomes of the miltuximab first in human trial and proposed study design for a phase I trial 89Zr/177Lu theranostic trial.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 261-261 ◽  
Author(s):  
Douglas Campbell ◽  
Dhanusha Sabanathan ◽  
Howard Gurney ◽  
David Gillatt ◽  
Marko Trifunovic ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase 1 ◽  
Standard Of Care ◽  
The Body ◽  
Whole Body ◽  
Chimeric Antibody ◽  
Pharmacokinetic Data ◽  
Post Dose ◽  
Before And After

261 Background: Miltuximab is a chimeric antibody targeting Glypican-1 which is overexpressed in prostate cancer. Miltuximab has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. Methods: Metastatic patients (prostate, pancreatic and bladder) were dosed with unlabelled Miltuximabfollowed by the infusion of 1 mg/250MBq 67Ga-Miltuximab. Patients underwent whole body gamma and SPECT/CT scans up to 144 hours post-infusion. Standard of care imaging was performed at least 14 days before and after participation. Safety was evaluated by an external monitoring committee. Total organ exposure was determined by dosimetry of whole-body gamma scans. Antibody pharmacokinetics were also determined. Results: 12 patients were enrolled into the trial. Miltuximabwas well tolerated and did not elicit any drug-related adverse reactions. Liver and spleen uptake of 67Ga-Miltuximabwas observed from 30 min to 72 hours post dose. Pre-infusion of unlabelled Miltuximab resulted in reduced liver accumulation and increased distribution in the rest of the body. Miltuximab targeting to sites of active progressive disease was observed in certain prostate cancer patients who had failed enzalutamide treatment. Dosimetry analysis combined with antibody pharmacokinetic data was used to establish safe dose limits for a Phase 1 study. Conclusions: This study is the first in human for Miltuximaband demonstrates its potential for further clinical evaluation as a theranostic in prostate cancers and formed the basis for a Phase I imaging and therapy study planned for 2019. This study will use 89Zr-labelled Miltuximab to screen eligible patients and confirm tumour localisation, followed by treatment with 177Lu-labelled Miltuximab. Clinical trial information: ACTRN12616000787482.

Estimation of [177Lu]PSMA-617 tumor uptake based on voxel-wise 3D Monte Carlo tumor dosimetry in patients with metastasized castration resistant prostate cancer

2020 ◽  
Vol 59 (05) ◽  
pp. 365-374
Author(s):  
Theresa Ida Götz ◽  
Elmar Wolfgang Lang ◽  
Olaf Prante ◽  
Michael Cordes ◽  
Torsten Kuwert ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Monte Carlo ◽  
Three Dimensional ◽  
Absorbed Dose ◽  
Whole Body ◽  
Patient Specific ◽  
Average Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Before And After

Abstract Objective Patients with advanced prostate cancer are suitable candidates for [177Lu]PSMA-617 therapy. Integrated SPECT/CT systems have the potential to improve the accuracy of patient-specific tumor dosimetry. We present a novel patient-specific Monte Carlo based voxel-wise dosimetry approach to determine organ and total tumor doses (TTD). Methods 13 patients with histologically confirmed metastasized castration-resistant prostate cancer were treated with a total of 18 cycles of [177Lu]PSMA-617 therapy. In each patient, dosimetry was performed after the first cycle of [177Lu]PSMA-617 therapy. Regions of interest were defined manually on the SPECT/CT images for the kidneys, spleen and all 295 PSMA-positive tumor lesions in the field of view. The absorbed dose to normal organs and to all tumor lesions were calculated by a three dimensional dosimetry method based on Monte Carlo Simulations. Results The average dose values yielded the following results: 2.59 ± 0.63 Gy (1.67–3.92 Gy) for the kidneys, 0.79 ± 0.46 Gy (0.31–1.90 Gy) for the spleen and 11.00 ± 11.97 Gy (1.28–49.10 Gy) for all tracer-positive tumor lesions. A trend towards higher TTD was observed in patients with Gleason Scores > 8 compared to Gleason Scores ≤ 8 and in lymph node metastases compared to bone metastases. A significant correlation was determined between the serum-PSA level before RLT and the TTD (r = –0.57, p < 0.05), as well as between the TTD with the percentage change of serum-PSA levels before and after therapy was observed (r = –0.57, p < 0.05). Patients with higher total tumor volumes of PSMA-positive lesions demonstrated significantly lower kidney average dose values (r = –0.58, p < 0.05). Conclusion The presented novel Monte Carlo based voxel-wise dosimetry calculates a patient specific whole-body dose distribution, thus taking into account individual anatomies and tissue compositions showing promising results for the estimation of radiation doses of normal organs and PSMA-positive tumor lesions.

Postprandial body protein synthesis and amino acid catabolism measured with leucine and phenylalanine-tyrosine tracers

2003 ◽  
Vol 284 (5) ◽  
pp. E1037-E1042 ◽  
Author(s):  
Paolo Tessari ◽  
Edward Kiwanuka ◽  
Michela Zanetti ◽  
Rocco Barazzoni
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Healthy Subjects ◽  
Fixed Ratio ◽  
Whole Body ◽  
Mixed Meal ◽  
Body Protein ◽  
Precursor Pool ◽  
Amino Acid Data ◽  
Before And After

Whether phenylalanine-tyrosine (Phe-Tyr) tracers yield estimates of postprandial protein synthesis comparable to those of the widely used leucine (Leu) tracer is unclear. We measured Leu oxidation (Ox), Phe hydroxylation (Hy), and their disposal into whole body protein synthesis before and after the administration of a mixed meal (62 kJ/kg body wt, 22% of energy as protein), over 4 h in healthy subjects. Both plasma and intracellular precursor pools were used. The amino acid data were extrapolated to body protein by assuming a fixed ratio of Leu to Phe in the proteins. In the postabsorptive state, whole body protein synthesis (expressed as mg · kg−1 · min−1) was similar between Leu and Phe-Tyr tracers irrespective of the precursor pool used. After the meal, Leu Ox, Phe Hy, and body protein synthesis increased ( P ≤ 0.01 vs. basal). With the use of intracellular precursor pools, the increase of protein synthesis with Phe-Tyr (+0.51 ±0.21 mg · kg−1 · min−1) and Leu tracers (+0.57 ± 0.14) were similar ( P = not significant). In contrast, with plasma pools the increase of protein synthesis was more than twofold greater with Phe-Tyr (+1.17 ± 0.19 mg · kg−1 · min−1) than that with Leu (0.50 ± 0.13 mg · kg−1 · min−1, P < 0.01). Direct correlations were found between Leu and Ox [using both plasma and intracellular pools ( r ≤ 0.65, P ≤ 0.01)] but not between Phe and either plasma or intracellular Hy. In conclusion, 1) Phe-Tyr and Leu tracers yield comparable estimates of body protein synthesis postprandially, provided that intracellular precursor pools are used; 2) both Leu Ox and Phe Hy are stimulated by a mixed meal; 3) Phe does not correlate with Hy, which might be better related to the (unknown) portal Phe.

scholarly journals Is there any relationship between PSA and increased peripheral CD4+CD25highFOX3+ Treg in prostate cancer patients?

2011 ◽  
Vol 1 (2) ◽  
pp. 75-82
Author(s):  
Yigit Akin ◽  
Sadi Koksoy ◽  
Selcuk Yucel ◽  
Tibet Erdogru ◽  
Mehmet Baykara
Keyword(s):  
Prostate Cancer ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Total Serum ◽  
Strong Positive Correlation ◽  
Peripheral Blood Mononuclear ◽  
Prostate Hyperplasia ◽  
Prostate Biopsies ◽  
Before And After ◽  
Benign Prostate

Introduction: The aims of this study were fi rst, to determine whether peripheral levels of CD4+CD25highFoxp3+ regulatory T cells (Treg) are elevated in Prostate Cancer (PCa) patients, and second, to determine the directcorrelation between peripheral Treg and total serum Prostate Specifi c Antigen (PSA) levels in these patients.Methods: Peripheral Blood Mononuclear Cells from 56 subjects undergoing diagnostic prostate biopsies (PSA ≥ 2.5 ng/ml) were analyzed for Treg numbers. The association between the peripheral Treg and serum PSA values was fi rst determined in the entire population, including people with no prostate pathology and PCa and Benign Prostate Hyperplasia (BPH) patients, and second, in nine PCa patients before and after curative prostatectomy.Results: This project was performed in Akdeniz University immunology laboratory and urology out patient clinic from 2008 to 2010. Peripheral Treg frequencies were signifi cantly increased in PCa patients (n = 19, 3.23 ± 1.59) compared with BPH patients (n = 27, 1.66 ± 0.80) and healthy subjects (n = 10, 1.08 ± 0.43) (p < 0.01). The percentage of Treg in BPH patients was also signifi cantly higher than that of healthy subjects (p < 0.01). Importantly, the increase in BPH and PCa patients paralleled the elevation in total serum PSA levels, demonstrating a strong positive correlation (r = 0.75; p < 0.01).Conclusion: These results demonstrate that peripheral Treg densities are correlated with PSA in BPH and PCa patients, suggesting that PSA may have a role in Treg induction and/or maintenance in Treg in these people.

scholarly journals Radiopharmacokinetic Modelling and Radiation Dose Assessment of 223ra Used for Treatment of Metastatic Castration Resistant Prostate Cancer

2020 ◽  
Author(s):  
Vera Höllriegl ◽  
Nina Petoussi-Henss ◽  
Juan Camilo Ocampo Ramos ◽  
Wei Bo Li
Keyword(s):  
Prostate Cancer ◽  
Dose Assessment ◽  
Radiological Protection ◽  
Bolus Administration ◽  
Time Activity ◽  
Biokinetic Model ◽  
Castration Resistant ◽  
Red Marrow ◽  
Dose Coefficients ◽  
Modelling Study

Abstract Purpose Ra-223-Dichloride (223Ra, Xofigo®) is used for treatment of patients suffering from castration-resistant metastatic prostate cancer. The objective of this work was to apply the most recent biokinetic model for radium and its progeny and dosimetric framework developed by the International Commission on Radiological Protection (ICRP) and to show their radiopharmacokinetic behaviour. Organ absorbed and equivalent doses after intravenous injection of 223Ra were estimated and compared to clinical data and other modelling study. Methods The most recent ICRP systemic biokinetic model of 223Ra and its progeny as well as the ICRP human alimentary tract model were applied for the radiopharmacokinetic modelling of Xofigo® biodistribution in patients after bolus administration. Independent kinetics was assumed for the progeny of 223Ra. The time activity curves for 223Ra were modelled and the time integrated activity coefficients, in the source regions for each progeny were determined. For estimating the organ absorbed doses, the Specific Absorbed Fractions (SAF) and dosimetric framework of ICRP were used together with the aforementioned values to estimate the organ absorbed and equivalent doses. Results The distribution of 223Ra after injection showed a rapid plasma clearance and a low urinary excretion. Main elimination was via faeces. Bone retention was found to be about 30% at 4 h post-injection. Similar tendencies were observed in clinic trials. The highest absorbed dose coefficients were found for bone endosteum, liver, and red marrow, followed by kidneys and colon. Conclusion The biokinetic modelling of 223Ra and its progeny may help to predict their distributions in patients after administration of Xofigo®. The organ dose coefficients of this work showed some variation to the values from clinical studies and of a previous compartmental modelling study. The dose to the bone endosteum was found to be lower by a factor of ca. 3 than previously estimated.

scholarly journals Early differences in dynamic uptake of 68Ga-PSMA-11 in primary prostate cancer: A test-retest study

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246394
Author(s):  
J. olde Heuvel ◽  
B. J. de Wit-van der Veen ◽  
M. Sinaasappel ◽  
C. H. Slump ◽  
M. P. M. Stokkel
Keyword(s):  
Prostate Cancer ◽  
Iliac Artery ◽  
Prostate Tumor ◽  
Whole Body ◽  
Time Interval ◽  
Tumor Uptake ◽  
Gluteal Muscle ◽  
Time Activity ◽  
Primary Prostate Cancer ◽  
Pet Ct

Introduction Dynamic PET/CT allows visualization of pharmacokinetics over the time, in contrast to static whole body PET/CT. The objective of this study was to assess 68Ga-PSMA-11 uptake in pathological lesions and benign tissue, within 30 minutes after injection in primary prostate cancer (PCa) patients in test-retest setting. Materials and methods Five patients, with biopsy proven PCa, were scanned dynamically in list mode for 30 minutes on a digital PET/CT-scanner directly after an intravenous bolus injection of 100 MBq 68Ga-PSMA-11. Approximately 45 minutes after injection a static whole body scan was acquired, followed by a one bed position scan of the pelvic region. The scans were repeated approximately four weeks later, without any intervention in between. Semi-quantitative assessment was performed using regions-of-interest in the prostate tumor, bladder, gluteal muscle and iliac artery. Time-activity curves were extracted from the counts in these regions and the intra-patient variability between both scans was assessed. Results The uptake of the iliac artery and gluteal muscle reached a plateau after 5 and 3 minutes, respectively. The population fell apart in two groups with respect to tumor uptake: in some patients the tumor uptake reached a plateau after 5 minutes, whereas in other patients the uptake kept increasing, which correlated with larger tumor volumes on PET/CT scan. Median intra-patient variation between both scans was 12.2% for artery, 9.7% for tumor, 32.7% for the bladder and 14.1% for the gluteal muscle. Conclusion Dynamic 68Ga-PSMA-11 PET/CT scans, with a time interval of four weeks, are reproducible with a 10% variation in uptake in the primary prostate tumor. An uptake plateau was reached for the iliac artery and gluteal muscle within 5 minutes post-injection. A larger tumor volume seems to be related to continued tumor uptake. This information might be relevant for both response monitoring and PSMA-based radionuclide therapies.

scholarly journals The Effect of Repeated Whole-Body Cryostimulation on the HSP-70 and Lipid Metabolisms in Healthy Subjects

2019 ◽  
pp. 419-429 ◽  
Author(s):  
A. LUBKOWSKA ◽  
I. BRYCZKOWSKA ◽  
Z. SZYGULA ◽  
C. GIEMZA ◽  
A. SKRZEK ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Prolonged Exposure ◽  
Whole Body ◽  
Cryogenic Temperatures ◽  
Hsp 70 ◽  
Protein Levels ◽  
Apolipoprotein A ◽  
Before And After ◽  
Simultaneous Decrease ◽  
Lipid Index

The aim of this study was to evaluate the effects of exposure to 30 daily whole body cryostimulation (WBC) on lipid metabolic parameters and serum HSP-70 concentration. The study involved 45 volunteers, homogeneous in terms of diet and daily physical activity. Blood samples were collected before and after the 10th, the 20th, and the 30th session and one month after the intervention. Total cholesterol, HDL, TG concentrations and Apolipoprotein A-I, ApoB and HSP-70 protein levels were determined in serum. Additionally, the LI (Lipid Index) and the LDL level were calculated. During exposure, positive changes in the lipid profile that included a decrease in the TCh, initiated after the 20th WBC session with a simultaneous decrease in TG and LDL levels, and an increase in the HDL concentration were observed. These changes were accompanied by a downward trend in the ApoB concentration and a decrease in the ApoB:ApoA-I ratio after 30 sessions. The nature of these changes persisted for a month after the exposure. The obtained results indicate metabolic benefits that result from prolonged exposure to cryogenic temperatures, confirming the postulate of using WBC in the regulation of lipid metabolism and the prevention of cardiovascular diseases.

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