Biokinetics of Americium-241 in the euryhaline diamond sturgeon Acipenser gueldenstaedtii following its uptake from water or food.

Americium-241 whole body and internal biokinetics were experimentally investigated in the euryhaline diamond sturgeon Acipenser gueldenstaedtii during its uptake from water and food, in fresh (FW) and brackish water (BW; 9 psu). Whole-body uptake rates of 241Am from water and subsequent depuration rates were quantified over 14 and 28 days, respectively, and assimilation efficiency (AE) of 241Am from diet (chironomid) was determined over 28 days. FW reduced the biological half-life of 241Am following aqueous uptake by an order of magnitude. In contrast BW greatly reduced 241Am assimilation efficiency (AE) from diet (chironomid) by several orders of magnitude (from an AE of 8.5% (FW) down to 0.003% (BW)). Hence, salinity per se is indicated as a major environmental variable in determining the radiological exposure of A. gueldenstaedtii to 241Am. During aqueous exposure BW appreciably increased 241Am activity concentrations in most body components, but aqueous or dietary exposure pathway at either salinity did not determine marked differences in how 241Am was distributed among six body components. The highly mineralized skin of A. gueldenstaedtii recurred as a major repository of 241Am in all experimental treatments, as high as 50% among body components, due to its internal transfer from diet, surface adsorption and/or active absorption from water. The indicated prominence of the aqueous, compared to the dietary, exposure pathway for 241Am accumulation by A. gueldenstaedtii suggests its radiological exposure would be enhanced by BW as it leads to its greater long-term retention, due to a much longer biological half-life.

Program for Determining the Dosimetric Contribution of Tc-99m Biokinetics in Estimating the Dose to the Heart of a Male Adult.

Purpose: To calculate the contribution of absorbed dose by organs in the biokinetics of Tc-99m when used for radiodiagnosis of the adult male heart employing a Matlab program. Methods: The absorbed self-dose of the adult male heart and absorbed dose by organs in the biokinetics of the heart when administering Tc-99m are estimated using the MIRD formalism and the Cristy-Eckerman representation, which have been employed to develop the algorithm in Matlab. Results: The results indicate that electron capture emissions of 1.446 (mGy/MBq) and Auger electrons of 0.062 (mGy/MBq) are entirely directed towards the target organ (heart) and contribute 29.33% and 1.25% respectively to its total dose. Additionally, the dosimetric contributions of biokinetic organs correspond to characteristic radiation emissions and gamma photons at 2.578 (mGy/MBq) for Tc-99m, representing 52.29% of its total dose. Conclusion: These dosimetric contributions are significant in estimating the total absorbed dose by the heart in adult males and should not be disregarded.

Simplified Assessment of Radioiodine Biokinetics for Thyroid Cancer Patients: A Practical Approach Using Continuous External Radiation Monitoring.

INTRODUCTION: The biokinetics of radioiodine (RAI) in thyroid cancer patients are complex. This study aims to develop a practical approach for assessing RAI biokinetics to predict patient discharge time and estimate radiation exposure to caregivers. METHODS: We retrospectively reviewed data from patients with differentiated thyroid carcinoma undergoing RAI treatment. Serial radiation dose rates were dynamically collected during hospitalization and fitted to a biexponential model to assess the biokinetic features: RAI uptake fraction of thyroid tissue (Ft) and effective half-life of extra-thyroid tissue (Tet). Correlations with 99mTc thyroid uptake ratio (TcUR), radiation retention ratio (RR), renal function, and body mass index (BMI) were analyzed. RESULTS: Thirty-five patients were enrolled. The derived Ft was 0.08 ± 0.06 and Tet was 7.57 ± 1.45 h. Pearson's correlation analysis revealed a significant association between Ft and both TcUR and RR (p < 0.05), while Tet correlated with renal function and BMI (p < 0.05). CONCLUSION: This novel and practical method assessing RAI biokinetics demonstrates consistency with other parameters and related studies, enhancing the model reliability. It shows promise in predicting an appropriate discharge time and estimating radiation exposure to caregivers, allowing for modifications to radiation protection precautions to follow ALARA principle and minimize the potential risks from radiation exposure.

Understanding the variable metal concentrations in estuarine oysters Crassostrea hongkongensis: A biokinetic analysis.

Understanding the metal concentrations in oysters is important because of its relevance to human health and biomonitoring. However, metal concentrations in oysters are highly variable in nature and not well explained by metal exposure. This study examined the metal contamination in farm oysters Crassostrea hongkongensis grown in Qinzhou Bay, south China. Cadmium (Cd), zinc (Zn), nickel (Ni), and copper (Cu) concentrations in the oysters varied between 7.9 and 72.2, 282-17003, 0.37-47.7 and 37-4012 µg g-1, respectively, showing large metal variability among different individuals. Oyster metal concentrations decreased with increasing body size and significantly higher levels were observed in wet season. Low salinity and slower oyster growth due to inferior growth conditions could be responsible for the elevated metal concentrations in the wet season. Biokinetic modeling showed that the coupling of ingestion rate and growth can cause 2.8-4.2 folds differences in the oyster Cd and Zn concentrations, respectively, suggesting the significant role of oyster bioenergetics in contributing to the metal variability. Modeling data revealed that Cd and Zn concentrations in oyster tissues reach maximum levels when oysters have their lowest growth efficiency. This suggests that any factors influencing the energy budget in oysters could simultaneously alter their metal concentrations, which might be the reason why oyster metal concentrations are so variable in the natural environment.

Tracking Nano- and Microplastics Accumulation and Egestion in a Marine Copepod by Novel Fluorescent AIEgens: Kinetic Modeling of the Rhythm Behavior.

Nano- and microplastics (NMPs) are now prevalent in the marine environment. This study quantified the uptake and depuration kinetics of spherical polystyrene NMPs of different particle sizes (200 nm/30 µm) and functional groups (-NH2/-COOH) in a temperate calanoid copepod Calanus sinicus (C. sinicus), which exhibited rhythmic feeding patterns in natural environments. Aggregated-induced emission (AIE) fluorescent probes were employed to track and quantify the kinetics of NMPs with excellent photostability and biocompatibility. The results showed that C. sinicus consumed all NMPs types, with preference of NMPs to small size and amino group. Increased diatom concentrations also inhibited the bioaccumulation of NMPs. Influenced by rhythmic behavior, the bioaccumulation of NMPs by C. sinicus was nonstationary during the 6 h uptake phase. After 1-3 h of rapid uptake, the body burden peaked and then slowly declined. During the 3 h depuration phase, C. sinicus rapidly and efficiently removed NMPs with a mean half-life of only 0.23 h. To further quantify the body burden of C. sinicus under the influence of rhythmic feeding behavior, a biokinetic model was established, and the Markov chain Monte Carlo method was used to estimate the parameter distribution. Our results highlighted that copepods exhibited unique rhythmic feeding behavior under environmentally relevant concentrations of NMPs exposure, which may influence the bioaccumulation, trophic transfer, and environmental fate of NMPs.

4-Aminobenzoic acid, 2-phenoxyethanol and iodine used as tracers in a short-term in vivo-kinetics study for tattoo ink ingredients: Mass spectrometry method development and validation.

Tattoos have been gaining popularity in recent years, leading to a growing interest in researching tattoo inks and the tattooing process itself. Since the exposure to soluble tattoo ink ingredients has not yet been investigated, we here present the method validation for a short-term biokinetics study on soluble tattoo ink ingredients. The three tracers 4-aminobenzoic acid (PABA), 2-phenoxyethanol (PEtOH) and iodine will be added to commercially available tattoo inks, which will subsequently be used on healthy study participants. Following the tattooing process, blood and urine will be sampled at specific time points and analysed for these tracers. For this purpose, a method using liquid chromatography separation coupled to a quadrupole time-of-flight mass spectrometer (LC-QTOF-MS) in positive and negative ESI mode for the quantification of PABA, PEtOH and selected metabolites and an inductively-coupled plasma (ICP)-MS method for the determination of iodine were developed and validated. For LC-QTOF-MS analysis, the most applicable additives for LC eluents (0.01 % formic acid for positive and 0.005 % acetic acid for negative mode) were identified. Protein precipitation with acetonitrile was chosen for sample preparation. The methods were validated for selectivity, specificity, carryover, linearity, limit of detection (LOD) and quantification (LOQ), matrix effects, accuracy and precision, stability under different conditions and dilution integrity according to national and international guidelines with an allowed maximum variation of ±15 %. The LC-QTOF-MS method met the imposed guideline criteria for most parameters, however, some metabolites showed strong matrix effects. Validation of the ICP-MS method revealed that the KED-H2 collision mode is superior to the standard analysis mode due to enhanced method accuracy. The methods were validated for the relevant matrices plasma, urine, tattoo ink and tattoo consumables and proved to be applicable for the main target substances in the short-term biokinetics study. A proof-of-concept study showed successful quantification of iodine and PABA metabolites. The PEtOH metabolite was also quantified, but showed strong matrix effects in urine. Therefore standard addition was selected as an alternative quantification method.

High nitrous oxide (N2O) greenhouse gas reduction potential of Pseudomonas sp. YR02 under aerobic condition.

Aerobic environments exist widely in wastewater treatment plants (WWTP) and are unfavorable for greenhouse gas nitrous oxide (N2O) reduction. Here, a novel strain Pseudomonas sp. YR02, which can perform N2O reduction under aerobic conditions, was isolated. The successful amplification of four denitrifying genes proved its complete denitrifying ability. The inorganic nitrogen (IN) removal efficiencies (NRE) were >98.0% and intracellular nitrogen and gaseous nitrogen account for 52.6-58.4% and 41.6-47.4% of input nitrogen, respectively. The priority of IN utilization was TAN > NO3--N > NO2--N. The optimal conditions for IN and N2O removal were consistent, except for the C/N ratio, which is 15 and 5 for IN and N2O removal, respectively. The biokinetic constants analysis indicated strain YR02 had high potential to treat high ammonia and dissolved N2O wastewater. Strain YR02 bioaugmentation mitigated 98.7% of N2O emission and improved 32% NRE in WWTP, proving its application potential for N2O mitigation.

Biokinetics of subacutely co-inhaled same size gold and silver nanoparticles.

BACKGROUND: Toxicokinetics of nanomaterials, including studies on the absorption, distribution, metabolism, and elimination of nanomaterials, are essential in assessing their potential health effects. The fate of nanomaterials after inhalation exposure to multiple nanomaterials is not clearly understood. METHODS: Male Sprague-Dawley rats were exposed to similar sizes of silver nanoparticles (AgNPs, 10.86 nm) and gold nanoparticles (AuNPs, 10.82 nm) for 28 days (6-h/day, 5-days/week for four weeks) either with separate NP inhalation exposures or with combined co-exposure in a nose-only inhalation system. Mass concentrations sampled from the breathing zone were AuNP 19.34 ± 2.55 µg/m3 and AgNP 17.38 ± 1.88 µg/m3 for separate exposure and AuNP 8.20 µg/m3 and AgNP 8.99 µg/m3 for co-exposure. Lung retention and clearance were previously determined on day 1 (6-h) of exposure (E-1) and on post-exposure days 1, 7, and 28 (PEO-1, PEO-7, and PEO-28, respectively). In addition, the fate of nanoparticles, including translocation and elimination from the lung to the major organs, were determined during the post-exposure observation period. RESULTS: AuNP was translocated to the extrapulmonary organs, including the liver, kidney, spleen, testis, epididymis, olfactory bulb, hilar and brachial lymph nodes, and brain after subacute inhalation and showed biopersistence regardless of AuNP single exposure or AuNP + AgNP co-exposure, showing similar elimination half-time. In contrast, Ag was translocated to the tissues and rapidly eliminated from the tissues regardless of AuNP co-exposure. Ag was continually accumulated in the olfactory bulb and brain and persistent until PEO-28. CONCLUSION: Our co-exposure study of AuNP and AgNP indicated that soluble AgNP and insoluble AuNP translocated differently, showing soluble AgNP could be dissolved into Ag ion to translocate to the extrapulmonary organs and rapidly removed from most organs except the brain and olfactory bulb. Insoluble AuNPs were continually translocated to the extrapulmonary organs, and they were not eliminated rapidly.

Patient-specific biokinetics and hybrid 2D/3D approach integration in OEDIPE software: Application to radioiodine therapy.

BACKGROUND: The progression of targeted radionuclide therapy requires the development of dosimetry software accounting for patient-specific biokinetics. New functionalities were thus developed in the OEDIPE software, to deal with multiple 3D images or multiple planar images and a SPECT image. MATERIEL & METHOD: Methods were implemented to recover patient biokinetics in volumes of interest. If several 3D SPECT images are available, they are registered to a reference CT scan. When several planar images and a single SPECT are available, the planar images are registered to the SPECT and counts of the planar images converted to activity. To validate these developments, six SPECT/CT and planar images of a Jaszczak phantom containing I-131 were acquired at different dates. Cumulated activity was estimated in each sphere using the SPECT/CT images only or the planar series associated to one SPECT/CT. Biokinetics and doses in lesions and in the lungs of a patient treated with I-131 for differentiated thyroid cancer were then estimated using four planar images and a SPECT/CT scan. Whole-body retention data were used to compare the biokinetics obtained from the planar and SPECT data. RESULTS: Activities and cumulated activities estimated using OEDIPE in the phantom spheres agreed well with the reference values for both approaches. Results obtained for the patient compared well with those derived from whole-body retention data. CONCLUSION: The implemented features allow automatic evaluation of patient-specific biokinetics from different series of patient images, enabling patient-specific dosimetry without the need for external software to estimate the cumulated activities in different VOIs.

Determinants of target absorbed dose in radionuclide therapy.

In radionuclide therapy, activity kinetics in tissues determine the absorbed doses administered and thus efficacy and side effects of treatment. The objective of this work was to derive expressions for the parameters affecting the absorbed dose to a target tissue for first-order activity kinetics. The activity uptake results from contributions from the first-pass activity flow through the target tissue preceding systemic equilibration and uptake after distribution of the administered compound in the body. The absorbed dose from uptake after equilibration is the product of the mean energy deposited per decay in the target tissue, the time integral of the plasma activity concentration, the plasma volume flow per unit target tissue mass, the probability of activity removal during passage, and the mean lifetime of activity in the target tissue. Quantitative analysis of the determinants of absorbed dose exemplarily for radioiodine therapy indicates that the high uptake often observed in Graves' disease must be associated with high tissue perfusion and removal probability and that administration of stable iodine increases mean lifetime. For therapies with long residence times of the active compound in the blood, such as radioiodine therapy, the contribution of the first-pass is small compared with uptake after equilibration. The relative first-pass contribution is higher for agents that are rapidly eliminated from the blood pool, such as radiolabelled somatostatin analogues, and may dominate after arterial application. Understanding the determining parameters in radionuclide therapy reveals dose-limiting factors and opens up opportunities to optimise and individualize therapy, potentially improving treatment success rates.

Team approach to osteoarthritis management: Viewpoints of biokineticists and physiotherapists in South Africa.

Background: The rehabilitative nature of biokinetics and physiotherapy in osteoarthritis management highlights a complex interaction between different professions to achieve effective outcomes for the patient. The success of a team approach is dependent on key competencies for optimal patient-focused care and appropriate cross-referral systems. Objectives: To explore and describe the viewpoints of biokineticists and physiotherapists regarding a team approach to osteoarthritis management in the South African public and private healthcare setting. Methods: A descriptive methodology with a convenience sampling technique was used. The target population consisted of biokineticists (n=47) and physiotherapists (n=165) located within the South African healthcare sectors. A self-administered, online questionnaire surveyed rehabilitative professionals' views of a team approach to osteoarthritis management. Results: There is no evidence that the biokineticists and physiotherapists differ with respect to how they rate the communication between team members in osteoarthritis management (p=0.68). Communication was viewed as neither of a high nor low quality by biokineticists (43%) and physiotherapists (36%). Biokineticists (54%) and physiotherapists (69%) felt adequately equipped on their understanding of the role of various healthcare professions involved in osteoarthritis management (p=0.22). However, 43% of rehabilitative professionals indicated that they had not been exposed to interprofessional education initiatives (p=0.61). Conclusion: Both professions were well-versed on the roles of various professions involved in osteoarthritis management, however, communication was not optimal. While this study creates an awareness of the benefits of team-based management for osteoarthritis, the findings could stimulate debate on the optimal implementation of key competencies required for effective teamwork, thereby facilitating patient-focused care and referral systems.

The consequence of head-loading on the neuro-musculoskeletal health of the ILembe District youth of KwaZulu-Natal.

Background: Head-loading, as a mode of transporting food, water and firewood, is a longstanding tradition assigned to female South African youth and has been associated with adverse health consequences. Objectives: This study determined the impact of head-loading on the neuromusculoskeletal health and proprioception of female South African youth. Method: This study comprised a counterbalanced, within-subject, single-factor experimental design which compared the changes that occurred when the same independent variable (head-loading) within two homogenous groups was measured in terms of the dependent variables (outcomes: neuromusculoskeletal pain and proprioception) at two time periods, before and after the introduction of the independent variable. A cohort of South African female youth (n = 100), aged 9-17 years, voluntarily partook in the study. The participants were randomly distributed into an experimental (n = 50) and a control (n = 50) group. The experimental group stood in a head-loaded state with their respective habitual head-load mass. Their proprioception measurements were compared during their unloaded versus loaded states, with the proprioceptive measurements including the total proprioception index, the anterior-posterior (front-back) index and the medial-lateral (side-to-side) index. Participants furthermore completed a head-loading health-related questionnaire. Results: Participants had a mean age of 12.3 ± 2.5 years, body mass of 44.4 ± 13.7 kg, stature of 145 ± 10 cm and a head-load mass of 8.0 ± 2.5 kg. Participants had poorer medial-lateral proprioception during head-loading as compared to their unloaded state (1.4 ± 0.8 as compared to 1.6 ± 0.9) (p < 0.05). Most youth (96%) experienced neuromusculoskeletal pain in their cervical vertebrae (40.9%), shoulders (27.3%), lumbar vertebrae (10.7%), arms (8.3%), legs (8.3%), knees (1.9%), fingers (1.5%), toes (0.5%) and thoracic vertebrae (0.5%) (χ2: p < 0.05). Conclusion: Head-loading adversely affects the medial-lateral proprioception and neuromusculoskeletal health of participants. Contribution: The findings of this study confirms that head-loading produces musculoskeletal pain.

Biokinetics and Internal Dosimetry of Tritiated Steel Particles.

Decommissioning fission and fusion facilities can result in the production of airborne particles containing tritium that could inadvertently be inhaled by workers directly involved in the operations, and potentially others, resulting in internal exposures to tritium. Of particular interest in this context, given the potentially large masses of material involved, is tritiated steel. The International Commission on Radiological Protection (ICRP) has recommended committed effective dose coefficients for inhalation of some tritiated materials, but not specifically for tritiated steel. The lack of a dose coefficient for tritiated steel is a concern given the potential importance of the material. To address this knowledge gap, a "dissolution" study, in vivo biokinetic study in a rodent model (1 MBq intratracheal instillation, 3-month follow-up) and associated state-of-the-art modelling were undertaken to derive dose coefficients for model tritiated steel particles. A committed effective dose coefficient for the inhalation of 3.3 × 10-12 Sv Bq-1 was evaluated for the particles, reflecting an activity median aerodynamic diameter (AMAD) of 13.3 µm, with the value for a reference AMAD for workers (5 µm) of 5.6 × 10-12 Sv Bq-1 that may be applied to occupational inhalation exposure to tritiated steel particles.

Methods of improving brain dose estimates for internally deposited radionuclides.

The US National Council on Radiation Protection and Measurements (NCRP) convened Scientific Committee 6-12 (SC 6-12) to examine methods for improving dose estimates for brain tissue for internally deposited radionuclides, with emphasis on alpha emitters. This Memorandum summarises the main findings of SC 6-12 described in the recently published NCRP Commentary No. 31, 'Development of Kinetic and Anatomical Models for Brain Dosimetry for Internally Deposited Radionuclides'. The Commentary examines the extent to which dose estimates for the brain could be improved through increased realism in the biokinetic and dosimetric models currently used in radiation protection and epidemiology. A limitation of most of the current element-specific systemic biokinetic models is the absence of brain as an explicitly identified source region with its unique rate(s) of exchange of the element with blood. The brain is usually included in a large source region calledOtherthat contains all tissues not considered major repositories for the element. In effect, all tissues inOtherare assigned a common set of exchange rates with blood. A limitation of current dosimetric models for internal emitters is that activity in the brain is treated as a well-mixed pool, although more sophisticated models allowing consideration of different activity concentrations in different regions of the brain have been proposed. Case studies for 18 internal emitters indicate that brain dose estimates using current dosimetric models may change substantially (by a factor of 5 or more), or may change only modestly, by addition of a sub-model of the brain in the biokinetic model, with transfer rates based on results of published biokinetic studies and autopsy data for the element of interest. As a starting place for improving brain dose estimates, development of biokinetic models with explicit sub-models of the brain (when sufficient biokinetic data are available) is underway for radionuclides frequently encountered in radiation epidemiology. A longer-term goal is development of coordinated biokinetic and dosimetric models that address the distribution of major radioelements among radiosensitive brain tissues.

Use of in vitro metabolism and biokinetics assays to refine predicted in vivo and in vitro internal exposure to the cosmetic ingredient, phenoxyethanol, for use in risk assessment.

A novel approach was developed to help characterize the biokinetics of the cosmetic ingredient, phenoxyethanol, to help assess the safety of the parent and its major stable metabolite. In the first step of this non-animal tiered approach, primary human hepatocytes were used to confirm or refute in silico predicted metabolites, and elucidate the intrinsic clearance of phenoxyethanol. A key result was the identification of the major metabolite, phenoxyacetic acid (PAA), the exposure to which in the kidney was subsequently predicted to far exceed that of phenoxyethanol in blood or other tissues. Therefore, a novel aspect of this approach was to measure in the subsequent step the formation of PAA in the cells dosed with phenoxyethanol that were used to provide points of departure (PoDs) and express the intracellular exposure as the Cmax and AUC24. This enabled the calculation of the intracellular concentrations of parent and metabolite at the PoD in the cells used to derive this value. These concentrations can be compared with in vivo tissue levels to conclude on the safety margin. The lessons from this case study will help to inform the design of other non-animal safety assessments.

Blood flow restriction training in South Africa - a panel discussion.

Background: Blood flow restriction (BFR) training uses a cuff to partially occlude venous blood flow and improve musculoskeletal training outcomes. Over the past 25 years, numerous studies have demonstrated its relative safety and efficacy. Objectives: Blood flow restriction training is under review by the Health Professions Council of South Africa due to safety and ethical concerns. The objective of this roundtable discussion is to gain better insight into the current use and perception of blood flow restriction training in South Africa. Formation of panel: The expert panel had experience with the use of BFR training and included one representative from each of the following professions, namely, sports medicine, physiotherapy and biokinetics. Discussion: The panellists provided their unique perspectives on BFR training, whilst reaching a relative consensus on its safety, screening, efficacy, and appropriate use. Agreement on appropriate loading and occlusion pressure protocols during different phases of rehabilitation was less clear. Conclusion: Although BFR is a safe and effective modality, the development of evidence-based protocols among different health professionals in South Africa is required to ensure good clinical practice.

Translational Development of a Zr-89-Labeled Inhibitor of Prostate-specific Membrane Antigen for PET Imaging in Prostate Cancer.

PURPOSE: We present here a Zr-89-labeled inhibitor of prostate-specific membrane antigen (PSMA) as a complement to the already established F-18- or Ga-68-ligands. PROCEDURES: The precursor PSMA-DFO (ABX) was used for Zr-89-labeling. This is not an antibody, but a peptide analogue of the precursor for the production of [177Lu]Lu-PSMA-617. The ligand [89Zr]Zr-PSMA-DFO was compared with [68Ga]Ga-PSMA-11 and [18F]F-JK-PSMA-7 in vitro by determination of the Kd value, cellular uptake, internalization in LNCaP cells, biodistribution studies with LNCaP prostate tumor xenografts in mice, and in vivo by small-animal PET imaging in LNCaP tumor mouse models. A first-in-human PET was performed with [89Zr]Zr-PSMA-DFO on a patient presenting with a biochemical recurrence after brachytherapy and an ambiguous intraprostatic finding with [18F]F-JK-PSMA-7 but histologically benign cells in a prostate biopsy 7 months previously. RESULTS: [89Zr]Zr-PSMA-DFO was prepared with a radiochemical purity ≥ 99.9% and a very high in vitro stability for up to 7 days at 37 °C. All radiotracers showed similar specific cellular binding and internalization, in vitro and comparable tumor uptake in biodistribution experiments during the first 5 h. The [89Zr]Zr-PSMA-DFO achieved significantly higher tumor/background ratios in LNCaP tumor xenografts (tumor/blood: 309 ± 89, tumor/muscle: 450 ± 38) after 24 h than [68Ga]Ga-PSMA-11 (tumor/blood: 112 ± 57, tumor/muscle: 58 ± 36) or [18F]F-JK-PSMA-7 (tumor/blood: 175 ± 30, tumor/muscle: 114 ± 14) after 4 h (p < 0.01). Small-animal PET imaging demonstrated in vivo that tumor visualization with [89Zr]Zr-PSMA-DFO is comparable to [68Ga]Ga-PSMA-11 or [18F]F-JK-PSMA-7 at early time points (1 h p.i.) and that PET scans up to 48 h p.i. clearly visualized the tumor at late time points. A late [89Zr]Zr-PSMA-DFO PET scan on a patient with biochemical recurrence (BCR) had demonstrated intensive tracer accumulation in the right (SUVmax 13.25, 48 h p.i.) and in the left prostate lobe (SUV max 9.47), a repeat biopsy revealed cancer cells on both sides. CONCLUSION: [89Zr]Zr-PSMA-DFO is a promising PSMA PET tracer for detection of tumor areas with lower PSMA expression and thus warrants further clinical evaluation.

Potential improvements in brain dose estimates for internal emitters.

BACKGROUND: Element-specific biokinetic models are used to reconstruct doses to systemic tissues from internal emitters. Typically, a systemic model for a radionuclide explicitly depicts only its dominant repositories. Remaining tissues and fluids are aggregated into a pool called Other tissue in which the radionuclide is assumed to be uniformly distributed. In the systemic biokinetic models used in radiation protection, the brain usually is addressed as an implicit mass fraction of Other tissue rather than an explicitly depicted repository. Due to increasing interest in radiation effects on the brain, efforts are underway to improve brain dosimetry for internal radiation sources. METHODS: We assessed potential improvements in brain dosimetry for internal emitters by explicitly modeling brain kinetics rather than treating the brain as a mass fraction of Other tissue. We selected 10 elements for which brain kinetics can be modeled using published biokinetic data. Injection dose coefficients were calculated for a relatively long-lived radioisotope of each element using each of two versions of the ICRP's latest systemic biokinetic model for the element, the original version and a modified version differing only in the treatment of brain. If the ICRP model contained an explicit brain pool, the modified version depicted brain instead as a mass fraction of Other tissue. If the ICRP model included brain in Other tissue, the modified version included an explicit brain pool with kinetics based on best available brain-specific data. RESULTS: The result for a given radionuclide is expressed as a ratio A:B, where A and B are the dose coefficients based on the versions of the model with and without an explicit brain pool, respectively. The following ratios A:B were obtained for the 10 radionuclides addressed here: 241Am, 0.13; 207Bi, 0.57; 234U, 0.81; 239Pu, 0.96; 203Hg (vapor), 1.4; 134Cs, 1.5; 54Mn, 1.7; 210Po, 1.7; 226Ra, 1.9; 210Pb, 3.3. These ratios indicate that a dose estimate for brain based on a biokinetic model with brain implicitly contained in Other tissue may substantially underestimate or substantially overestimate a dose estimate that reflects best available brain-specific biokinetic data. Of course, the reliability of the latter estimate depends on the quality of the underlying biokinetic data. CONCLUSIONS: Where feasible, the brain should be depicted explicitly in biokinetic models used in epidemiological studies addressing adverse effects of ionizing radiation.

Biokinetics and Dosimetry of 177Lu-Pentixather.

The chemokine receptor 4 (CXCR4), which is overexpressed in many solid and hematologic malignancies, can be targeted for radiopeptide therapy via the antagonist pentixather. The biokinetics and dosimetry of 177Lu-pentixather and 90Y-pentixather were analyzed in this study. Methods: This retrospective study was a standardized reevaluation of data collected for treatment planning. Nineteen patients with complete sets of planar whole-body scans over at least 4 d and a single SPECT/CT scan after administration of 200 MBq of 177Lu-pentixather were included. Kinetics were measured in the whole body, in tissues with activity retention, and in 10 individuals in the blood. Time-integrated activity coefficients and tissue-absorbed doses were derived. Results: Increased uptake of pentixather was observed in the kidneys, liver, spleen, and bone marrow, inducing respective median absorbed doses of 0.91 Gy (range, 0.38-3.47 Gy), 0.71 Gy (range, 0.39-1.17 Gy), 0.58 Gy (range, 0.34-2.26 Gy), and 0.47 Gy (range, 0.14-2.33 Gy) per GBq of 177Lu-pentixather and 3.75 Gy (range, 1.48-12.2 Gy), 1.61 Gy (range, 1.14-2.97 Gy), 1.66 Gy (range, 0.97-6.69 Gy), and 1.06 Gy (range, 0.27-4.45 Gy) per GBq of 90Y-pentixather. In most tissues, activity increased during the first day after the administration of 177Lu-pentixather and afterward decayed with mean effective half-lives of 41 ± 10 h (range, 24-64 h) in the kidneys and median half-lives of 109, 86, and 92 h in the liver, spleen, and bone marrow, respectively. Maximum uptake per kidney was 2.2% ± 1.0% (range, 0.6%-5.1%). In organs showing no specific uptake, absorbed doses exceeding 0.3 Gy/GBq of 90Y-pentixather were estimated for the urinary bladder and for tissues adjacent to accumulating organs such as the adrenal glands, bone surface, and gallbladder. Dose estimates for tumors and extramedullary lesions ranged from 1.5 to 18.2 Gy/GBq of 90Y-pentixather. Conclusion: In patients with hematologic neoplasms, absorbed doses calculated for bone marrow and extramedullary lesions are sufficient to be effective as an adjunct to high-dose chemotherapies before stem cell transplantation.

The consequence of head-loading on the neuro-musculoskeletal health of the ILembe District youth of KwaZulu-Natal

Background: Head-loading, as a mode of transporting food, water and firewood, is a longstanding tradition assigned to female South African youth and has been associated with adverse health consequences. Objectives: This study determined the impact of head-loading on the neuromusculoskeletal health and proprioception of female South African youth. Method: This study comprised a counterbalanced, within-subject, single-factor experimental design which compared the changes that occurred when the same independent variable (head-loading) within two homogenous groups was measured in terms of the dependent variables (outcomes: neuromusculoskeletal pain and proprioception) at two time periods, before and after the introduction of the independent variable. A cohort of South African female youth (n = 100), aged 9­17 years, voluntarily partook in the study. The participants were randomly distributed into an experimental (n = 50) and a control (n = 50) group. The experimental group stood in a head-loaded state with their respective habitual head-load mass. Their proprioception measurements were compared during their unloaded versus loaded states, with the proprioceptive measurements including the total proprioception index, the anterior­posterior (front­back) index and the medial­lateral (side-to-side) index. Participants furthermore completed a head-loading health-related questionnaire. Results: Participants had a mean age of 12.3 ± 2.5 years, body mass of 44.4 ± 13.7 kg, stature of 145 ± 10 cm and a head-load mass of 8.0 ± 2.5 kg. Participants had poorer medial­lateral proprioception during head-loading as compared to their unloaded state (1.4 ± 0.8 as compared to 1.6 ± 0.9) (p < 0.05). Most youth (96%) experienced neuromusculoskeletal pain in their cervical vertebrae (40.9%), shoulders (27.3%), lumbar vertebrae (10.7%), arms (8.3%), legs (8.3%), knees (1.9%), fingers (1.5%), toes (0.5%) and thoracic vertebrae (0.5%) (χ2: p < 0.05). Conclusion: Head-loading adversely affects the medial­lateral proprioception and neuromusculoskeletal health of participants.