A re-activation model for 169Yb intensity modulated brachytherapy sources accounting for spatiotemporal isotopic composition.

BACKGROUND: Intensity modulated brachytherapy based on partially shielded intracavitary and interstitial applicators is possible with a cost-effective 169Yb production method. 169Yb is a traditionally expensive isotope suitable for this purpose, with an average γ-ray energy of 93 keV. Re-activating a single 169Yb source multiple times in a nuclear reactor between clinical uses was shown to theoretically reduce cost by approximately 75% relative to conventional single-activation sources. With re-activation, substantial spatiotemporal variation in isotopic source composition is expected between activations via 168Yb burnup and 169Yb decay, resulting in time dependent neutron transmission, precursor usage, and reactor time needed per re-activation. PURPOSE: To introduce a generalized model of radioactive source production that accounts for spatiotemporal variation in isotopic source composition to improve the efficiency estimate of the 169Yb production process, with and without re-activation. METHODS AND MATERIALS: A time-dependent thermal neutron transport, isotope transmutation, and decay model was developed. Thermal neutron flux within partitioned sub-volumes of a cylindrical active source was calculated by raytracing through the spatiotemporal dependent isotopic composition throughout the source, accounting for thermal neutron attenuation along each ray. The model was benchmarked, generalized, and applied to a variety of active source dimensions with radii ranging from 0.4 to 1.0 mm, lengths from 2.5 to 10.5 mm, and volumes from 0.31 to 7.85 mm3, at thermal neutron fluxes from 1 × 1014 to 1 × 1015 n cm-2 s-1. The 168Yb-Yb2O3 density was 8.5 g cm-3 with 82% 168Yb-enrichment. As an example, a reference re-activatable 169Yb active source (RRS) constructed of 82%-enriched 168Yb-Yb2O3 precursor was modeled, with 0.6 mm diameter, 10.5 mm length, 3 mm3 volume, 8.5 g cm-3 density, and a thermal neutron activation flux of 4 × 1014 neutrons cm-2 s-1. RESULTS: The average clinical 169Yb activity for a 0.99 versus 0.31 mm3 source dropped from 20.1 to 7.5 Ci for a 4 × 1014 n cm-2 s-1 activation flux and from 20.9 to 8.7 Ci for a 1 × 1015 n cm-2 s-1 activation flux. For thermal neutron fluxes ≥2 × 1014 n cm-2 s-1, total precursor and reactor time per clinic-year were maximized at a source volume of 0.99 mm3 and reached a near minimum at 3 mm3. When the spatiotemporal isotopic composition effect was accounted for, average thermal neutron transmission increased over RRS lifetime from 23.6% to 55.9%. A 28% reduction (42.5 days to 30.6 days) in the reactor time needed per clinic-year for the RRS is predicted relative to a model that does not account for spatiotemporal isotopic composition effects. CONCLUSIONS: Accounting for spatiotemporal isotopic composition effects within the RRS results in a 28% reduction in the reactor time per clinic-year relative to the case in which such changes are not accounted for. Smaller volume sources had a disadvantage in that average clinical 169Yb activity decreased substantially below 20 Ci for source volumes under 1 mm3. Increasing source volume above 3 mm3 adds little value in precursor and reactor time savings and has a geometric disadvantage.

Chemokine Receptor CXCR4 Radioligand Targeted Therapy Using 177Lutetium-pentixather for Pulmonary Neuroendocrine Cancers.

Intermediate to high-grade lung neuroendocrine tumors (NETs; i.e., atypical carcinoid tumors) and neuroendocrine carcinomas (NECs) are currently difficult to cure. These tumors were found to express the CXCR4 G-protein coupled receptor that can be targeted with radioligands. PCR and flow cytometric analysis of lung NET and NEC cell lines using an anti-CXCR4 antibody demonstrated that all cell lines tested expressed CXCR4. PET/CT imaging with 68Galium-pentixafor in mouse xenografts of NETs and NECs verified tumor targeting that was blocked by a CXCR4 agonist. Clonogenic survival analysis demonstrated a more than additive enhancement of killing when 1 µM auranofin (a thioredoxin reductase inhibitor) was used as a radiosensitizer in combination with 177Lu-pentixather (10 µCi). DMS273 small cell lung cancer xenografts in female nude mice treated with 25 µCi/g 177Lu-pentixather induced inhibition of tumor growth and resulted in an increase in overall survival without causing unacceptable normal tissue toxicities. Immunohistochemical staining of 95 retrospective human samples (containing 90 small cell lung carcinomas) demonstrated 84% CXCR4 positivity. In a multivariable analysis of this cohort that included age, gender, stage, primary site, SSTR2 status, and CXCR4 status, Cox regression models determined that only distant metastasis at presentation (P < 0.01) and a CXCR4 H-score >30 (P = 0.04) were significantly associated with reduced survival. Prospective clinical testing of patient tumors identified CXCR4-positivity in 76% of 21 NECs, 67% of 15 lung NETs (including 8 of 10 atypical carcinoids), and 0% of 25 non-lung NETs (including 5 NETS G3s). These data support the hypothesis that CXCR4-targeted theranostics can be utilized effectively for select NETs and NECs.

AAPM Medical Physics Practice Guideline 14.a: Yttrium-90 microsphere radioembolization.

Radioembolization using Yttrium-90 (90 Y) microspheres is widely used to treat primary and metastatic liver tumors. The present work provides minimum practice guidelines for establishing and supporting such a program. Medical physicists play a key role in patient and staff safety during these procedures. Products currently available are identified and their properties and suppliers summarized. Appropriateness for use is the domain of the treating physician. Patient work up starts with pre-treatment imaging. First, a mapping study using Technetium-99m (Tc-99m ) is carried out to quantify the lung shunt fraction (LSF) and to characterize the vascular supply of the liver. An MRI, CT, or a PET-CT scan is used to obtain information on the tumor burden. The tumor volume, LSF, tumor histology, and other pertinent patient characteristics are used to decide the type and quantity of 90 Y to be ordered. On the day of treatment, the appropriate dose is assayed using a dose calibrator with a calibration traceable to a national standard. In the treatment suite, the care team led by an interventional radiologist delivers the dose using real-time image guidance. The treatment suite is posted as a radioactive area during the procedure and staff wear radiation dosimeters. The treatment room, patient, and staff are surveyed post-procedure. The dose delivered to the patient is determined from the ratio of pre-treatment and residual waste exposure rate measurements. Establishing such a treatment modality is a major undertaking requiring an institutional radioactive materials license amendment complying with appropriate federal and state radiation regulations and appropriate staff training commensurate with their respective role and function in the planning and delivery of the procedure. Training, documentation, and areas for potential failure modes are identified and guidance is provided to ameliorate them.

Pre-clinical evaluation of biomarkers for the early detection of nephrotoxicity following alpha-particle radioligand therapy.

PURPOSE: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as an additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLT nephrotoxicity. METHODS: A bifunctional cyclic peptide, melanocortin 1 ligand (MC1L), labeled with [203Pb]Pb-MC1L, was used for [212Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [212Pb]Pb-MC1L in a dose-escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. RESULTS: Biodistribution analysis identified [212Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [212Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [212Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. CONCLUSION: Urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.

Head and Neck Cancer Segmentation in FDG PET Images: Performance Comparison of Convolutional Neural Networks and Vision Transformers.

Convolutional neural networks (CNNs) have a proven track record in medical image segmentation. Recently, Vision Transformers were introduced and are gaining popularity for many computer vision applications, including object detection, classification, and segmentation. Machine learning algorithms such as CNNs or Transformers are subject to an inductive bias, which can have a significant impact on the performance of machine learning models. This is especially relevant for medical image segmentation applications where limited training data are available, and a model's inductive bias should help it to generalize well. In this work, we quantitatively assess the performance of two CNN-based networks (U-Net and U-Net-CBAM) and three popular Transformer-based segmentation network architectures (UNETR, TransBTS, and VT-UNet) in the context of HNC lesion segmentation in volumetric [F-18] fluorodeoxyglucose (FDG) PET scans. For performance assessment, 272 FDG PET-CT scans of a clinical trial (ACRIN 6685) were utilized, which includes a total of 650 lesions (primary: 272 and secondary: 378). The image data used are highly diverse and representative for clinical use. For performance analysis, several error metrics were utilized. The achieved Dice coefficient ranged from 0.833 to 0.809 with the best performance being achieved by CNN-based approaches. U-Net-CBAM, which utilizes spatial and channel attention, showed several advantages for smaller lesions compared to the standard U-Net. Furthermore, our results provide some insight regarding the image features relevant for this specific segmentation application. In addition, results highlight the need to utilize primary as well as secondary lesions to derive clinically relevant segmentation performance estimates avoiding biases.

Pre-clinical Evaluation of Biomarkers for Early Detection of Nephrotoxicity Following Alpha-particle Radioligand Therapy.

Purpose: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLTs nephrotoxicity. Methods: A bifunctional cyclic peptide, melanocortin ligand-1(MC1L), labeled with [ 203 Pb]Pb-MC1L, was used for [ 212 Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [ 212 Pb]Pb-MC1L in a dose escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. Results: Biodistribution analysis identified [ 212 Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [ 212 Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary Neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [ 212 Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. Conclusion: urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.

Radiation Safety Considerations of Household Waste Disposal After Release of Patients Who Have Received [177Lu]Lu-PSMA-617.

Patients with metastatic prostate cancer are more likely than other groups to present for radiopharmaceutical therapy with urinary incontinence due to complications from prior local prostate cancer treatment. A consequence of urinary incontinence in patients receiving radiopharmaceutical therapy is the potential production of contaminated solid waste, which must be managed by the licensee and, at home, managed by and disposed of by the patient. Prolonging the patient stay in the treating facility after radiopharmaceutical therapy administration, until the first urinary void or potentially overnight, may moderately reduce the quantity of contaminated waste being managed by the patient at home. However, this approach does not fully mitigate the need for a patient waste-management strategy. In this brief communication, the relative radiation safety merits of contaminated waste disposal in the normal household waste stream in comparison to other waste management strategies are evaluated.

Multicenter Evaluation of Frequency and Impact of Activity Infiltration in PET Imaging, Including Microscale Modeling of Skin-Absorbed Dose.

There has been significant recent interest in understanding both the frequency of nuclear medicine injection infiltration and the potential for negative impact, including skin injury. However, no large-scale study has yet correlated visualized injection site activity with actual activity measurement of an infiltrate. Additionally, current skin dosimetry approaches lack sufficient detail to account for critical factors that impact the dose to the radiosensitive epidermis. Methods: From 10 imaging sites, 1,000 PET/CT patient studies were retrospectively collected. At each site, consecutive patients with the injection site in the field of view were used. The radiopharmaceutical, injected activity, time of injection and imaging, injection site, and injection method were recorded. Net injection site activity was calculated from volumes of interest. Monte Carlo image-based absorbed dose calculations were performed using the actual geometry from a patient with a minor infiltration. The simulation model used an activity distribution in the skin microanatomy based on known properties of subcutaneous fat, dermis, and epidermis. Simulations using several subcutaneous fat-to-dermis concentration ratios were performed. Absorbed dose to the epidermis, dermis, and fat were calculated along with relative γ- and ß-contributions, and these findings were extrapolated to a hypothetical worst-case (470 MBq) full-injection infiltration. Results: Only 6 of 1,000 patients had activity at the injection site in excess of 370 kBq (10 µCi), with no activities greater than 1.7 MBq (45 µCi). In 460 of 1,000 patients, activity at the injection site was clearly visualized. However, quantitative assessment of activities averaged only 34 kBq (0.9 µCi), representing 0.008% of the injected activity. Calculations for the extrapolated 470-MBq infiltration resulted in a hypothetical absorbed dose to the epidermis of below 1 Gy, a factor of 2 lower than what is required for deterministic skin reactions. Analysis of the dose distribution demonstrates that the dermis acts as a ß-shield for the radiation-sensitive epidermis. Dermal shielding is highly effective for low-energy 18F positrons but less so with the higher-energy positrons of 68Ga. Conclusion: When quantitative activity measurement criteria are used rather than visual, the frequency of PET infiltration appears substantially below frequencies previously published. Shallow doses to the epidermis from infiltration events are also likely substantially lower than previously reported because of absorption of ß-particles in the dermis.

Impact of radiopharmaceutical therapy (177Lu, 225Ac) microdistribution in a cancer-associated fibroblasts model.

BACKGROUND: The aim of this study is to elucidate the difference in absorbed dose (Dabs) patterns in radiopharmaceutical therapies between alpha emitters (225Ac) and beta emitters (177Lu) when targeting cancer-associated fibroblasts (CAF) or tumor cells. Five spherical models with 3 mm diameter were created, representing spherical tumor masses that contain tumor clusters, interspersed with CAFs. The mean distance from a tumor cell to the nearest CAF (Lmean) varied throughout these models from 92 to 1030 µm. Dabs calculations were performed while selecting either CAFs or tumor cells as sources, with Convolution/Superposition with 177Lu and Monte Carlo simulations (GATE) with 225Ac. Analyses were conducted with Dose Volume Histograms and efficacy ratios (ER), which represents the ratio of mean Dabs that is deposited in the target volume. RESULTS: 225Ac is the most optimal radionuclide when CAFs are both targeted and irradiating themselves, as ERs increase from 1.5 to 3.7 when Lmean increases from 92 to 1030 µm. With 177Lu, these numbers vary from 1.2 to 2.7. Conversely, when CAFs are sources and tumors are targets with 225Ac, ERs decreased from 0.8 to 0.1 when Lmean increases from 92 to 1030 µm. With 177Lu, these numbers vary from 0.9 to 0.3 CONCLUSION: When targeting CAFs to irradiate tumors, the efficacy of using 225Ac decreases as the average size of the tumor clusters (or Lmean) increases. In such situations, 177Lu will be more effective than 225Ac when targeting CAFs due to the longer beta particle range.

Practical Considerations for Implementation of 177Lu-DOTATATE Neuroendocrine Tumor Treatment Programs.

The 2018 FDA approval of 177Lu-DOTATATE for the treatment of somatostatin receptor-positive (SSTR) neuroendocrine tumors (NETs) represents a paradigm shifting approach to cancer treatments around the globe. Gastroenteropancreatic (GEP) NETs overexpress the somatostatin subtype receptor 2, which is now exploited for receptor-based imaging and therapy, thus generating significant progress in the diagnosis and treatment of this orphan disease. The recent FDA approval of receptor-based PET radiopharmaceuticals and a new peptide receptor radiopharmaceutical therapy (PRRT), 177Lu-DOTATATE, has dramatically impacted NET patient management. The focus of this paper is to review clinical considerations associated with implementing a 177Lu-DOTATATE program. We review receptor-based NET radiopharmaceuticals, 177Lu-DOTATATE patient selection criteria, administration methods, clinical, regulatory, and radiation safety considerations, technical factors, tissue dosimetry, and reimbursement guidelines.

The Impact of Radiopharmaceutical Therapy on Renal Function.

Radiopharmaceuticals used for cancer therapy are highly selective, designed to kill malignant cells and spare healthy tissues. Side effect rates are generally less than other treatments, but it is still the utmost concern to minimize normal organ toxicity and maximize radiation dose to the target lesions in applying radiopharmaceutical therapies (RPTs). Most commonly affected normal organs include bone marrow, kidneys and liver. The impact of RPTs to renal function is generally considered low. Peptide receptor radionuclide therapy (PRRT) using somatostatin radiopharmaceuticals, particularly 90Y-DOTATOC, has the potential to induce nephrotoxicity. This is because PRRT radiopharmaceuticals are primarily cleared thorough glomerular filtration and reabsorption/retainment of them at the renal proximal tubules exposes kidneys to additional radiation. Amino acid co-infusion is the standard regimen for competitive inhibition of tubular reabsorption of PRRT radiopharmaceuticals to mitigate nephrotoxicity. Other measures to protect renal function include hydration, use of plasma expander or radioprotectant, personalized renal dosimetry to limit renal radiation dose and close monitoring of renal function. Limited data suggest alpha emitter PRRT radiopharmaceuticals have less impact on kidney function compared to beta emitter PRRT, but more studies are needed for long term renal toxicity. 131I-MIBG is primarily excreted unchanged thorough the kidneys but renal absorbed dose is low and potential toxicities to the bone marrow and lungs are the most significant clinical concerns. Other RPTs that are not mainly cleared through kidneys such as 223Ra or radioimmunotherapy have no concern for kidney toxicity.

SIR-Spheres Activity Measurements Reveal Systematic Miscalibration.

The purpose of this work was to perform an independent and National Institute of Standards and Technology-traceable activity measurement of 90Y SIR-Spheres (Sirtex). γ-spectroscopic measurements of the 90Y internal pair production decay mode were made using a high-purity germanium detector. Methods: Measured annihilation radiation detection rates were corrected for radioactive decay during acquisition, dead time, source attenuation, and source geometry effects. Detection efficiency was determined by 2 independent and National Institute of Standards and Technology-traceable methods. Results: Measured SIR-Spheres vials (n = 5) contained more activity than specified by the manufacturer calibration; on average, the ratio of measured activity to calibrated was 1.233 ± 0.030. Activity measurements made using 2 distinct efficiency calibration methods agreed within 1%. Conclusion: The primary SIR-Spheres activity calibration appears to be a significant underestimate of true activity.

Quantification of uptake in pelvis F-18 FLT PET-CT images using a 3D localization and segmentation CNN.

PURPOSE: The purpose of this work was to develop and validate a deep convolutional neural network (CNN) approach for the automated pelvis segmentation in computed tomography (CT) scans to enable the quantification of active pelvic bone marrow by means of Fluorothymidine F-18 (FLT) tracer uptake measurement in positron emission tomography (PET) scans. This quantification is a critical step in calculating bone marrow dose for radiopharmaceutical therapy clinical applications as well as external beam radiation doses. METHODS: An approach for the combined localization and segmentation of the pelvis in CT volumes of varying sizes, ranging from full-body to pelvis CT scans, was developed that utilizes a novel CNN architecture in combination with a random sampling strategy. The method was validated on 34 planning CT scans and 106 full-body FLT PET-CT scans using a cross-validation strategy. Specifically, two different training and CNN application options were studied, quantitatively assessed, and statistically compared. RESULTS: The proposed method was able to successfully locate and segment the pelvis in all test cases. On all data sets, an average Dice coefficient of 0.9396 ± $\pm$ 0.0182 or better was achieved. The relative tracer uptake measurement error ranged between 0.065% and 0.204%. The proposed approach is time-efficient and shows a reduction in runtime of up to 95% compared to a standard U-Net-based approach without a localization component. CONCLUSIONS: The proposed method enables the efficient calculation of FLT uptake in the pelvis. Thus, it represents a valuable tool to facilitate bone marrow preserving adaptive radiation therapy and radiopharmaceutical dose calculation. Furthermore, the method can be adapted to process other bone structures as well as organs.

Monte Carlo evaluation of hypothetical long axial field-of-view PET scanner using GE Discovery MI PET front-end architecture.

PURPOSE: The development of total-body PET scanners is of growing interest in the PET community. Investigation into the imaging properties of a hypothetical extended axial field-of-view (AFOV) GE Healthcare SiPM-based Discovery MI (DMI) system architecture has not yet been performed. In this work, we assessed its potential as a whole-body scanner using Monte Carlo simulations. The aim of this work was to (1) develop and validate a Monte Carlo model of a four-ring scanner and (2) extend its AFOV up to 2 m to evaluate performance gain through NEMA-based evaluation. METHODS: The DMI four-ring geometry and its pulse digitization scheme were modeled within the GATE Monte Carlo platform using published literature. The GATE scanner model was validated by comparing results against published NEMA performance measurements. Following the validation of the four-ring model, the model was extended to simulate 8-, 20-, 30-, and 40-ring systems. Spatial resolution, sensitivity, NECR, and scatter fraction were characterized with modified NEMA NU-2 2018 standards; however, the image quality measurements were not acquired due to computational limitations. Spatial resolutions were simulated for all scanner ring configurations using point sources to examine the effects of parallax errors. NEMA count rates were estimated using a standard 70 cm scatter phantom and an extended version of scatter phantom of length 200 cm with (1-800) MBq of 18 F for all scanners. Sensitivity was evaluated using NEMA methods with a 70 cm standard and a 200 cm long line source. RESULTS: The average FWHM of the radial/tangential/axial spatial resolution reconstructed with filtered back-projection at 1 and 10 cm from the scanner center were 3.94/4.10/4.41 mm and 5.29/4.89/5.90 mm for the four-ring scanner. Sensitivity was determined to be 14.86 cps/kBq at the center of the FOV for the four-ring scanner using a 70 cm line source. Sensitivity enhancement up to 21-fold and 60-fold were observed for 1 and 2 m AFOV scanners compared to four-ring scanner using a 200 cm long line source. Spatial resolution simulations in a 2 m AFOV scanner suggest a maximum degradation of ∼23.8% in the axial resolution compared to the four-ring scanner. However, the transverse resolution was found to be relatively constant when increasing the axial acceptance angle up to ±70°. The peak NECR was 212.92 kcps at 22.70 kBq/ml with a scatter fraction of 38.9% for a four-ring scanner with a 70 cm scatter phantom. Comparison of peak NECR using the 200 cm long scatter phantom relative to the four-ring scanner resulted in a NECR gain of 15 for the 20-ring and 28 for the 40-ring geometry. Spatial resolution, sensitivity, and scatter fraction showed an agreement within ∼7% compared with published measured values. CONCLUSIONS: The four-ring DMI scanner simulation was successfully validated against published NEMA measurements. Sensitivity and NECR performance of extended 1 and 2 m AFOV scanners based upon the DMI architecture were subsequently simulated. Increases in sensitivity and count-rate performance are consistent with prior simulation studies utilizing extensions of the Siemens mCT architecture and published NEMA measurements with the uEXPLORER system.

Tumor Response to Radiopharmaceutical Therapies: The Knowns and the Unknowns.

Radiopharmaceutical therapy (RPT) is defined as the delivery of radioactive atoms to tumor-associated targets. In RPT, imaging is built into the mode of treatment since the radionuclides used in RPT often emit photons or can be imaged using a surrogate. Such imaging may be used to estimate tumor-absorbed dose. We examine and try to elucidate those factors that impact the absorbed dose-versus-response relationship for RPT agents. These include the role of inflammation- or immune-mediated effects, the significance of theranostic imaging, radiobiology, differences in dosimetry methods, pharmacokinetic differences across patients, and the impact of tumor hypoxia on response to RPT.

Dosimetry for Radiopharmaceutical Therapy: Current Practices and Commercial Resources.

With the ongoing dramatic growth of radiopharmaceutical therapy, research and development in internal radiation dosimetry continue to advance both at academic medical centers and in industry. The basic paradigm for patient-specific dosimetry includes administration of a pretreatment tracer activity of the therapeutic radiopharmaceutical; measurement of its time-dependent biodistribution; definition of the pertinent anatomy; integration of the measured time-activity data to derive source-region time-integrated activities; calculation of the tumor, organ-at-risk, and/or whole-body absorbed doses; and prescription of the therapeutic administered activity. This paper provides an overview of the state of the art of patient-specific dosimetry for radiopharmaceutical therapy, including current methods and commercially available software and other resources.