188Re image performance assessment using small animal multi-pinhole SPECT/PET/CT system

PurposeThe goal of this study was to investigate the performance of a pre-clinical SPECT/PET/CT system for ¹⁸⁸Re imaging.MethodsPhantom experiments were performed aiming to assess the characteristics of two multi-pinhole collimators: ultra-high resolution collimator (UHRC) and high-energy ultra high resolution collimator (HE-URHC) for imaging ¹⁸⁸Re. The spatial resolution, image contrast and contrast-to-noise ratio (CNR) were investigated using micro-Jaszczak phantoms. Additionally, the quantification accuracy of ¹⁸⁸Re images was evaluated using two custom-designed phantoms. The ¹⁸⁸Re images were compared to those obtained with ^99mTc (gold standard); the acquired energy spectra were analyzed and Monte-Carlo simulations of the UHRC were performed. To verify our findings, a C57BL/6-mouse was injected with ¹⁸⁸Re-microspheres and scanned with both collimators.ResultsThe spatial resolution achieved in ¹⁸⁸Re images was comparable to that of ^99mTc. Acquisitions using HE-UHRC yielded ¹⁸⁸Re images with higher contrast and CNR than UHRC. Studies of quantitative accuracy of ¹⁸⁸Re images resulted in <10% errors for both collimators when the activity was calculated within a small VOI around the object of interest. Similar quantification accuracy was achieved for ^99mTc. However, ¹⁸⁸Re images showed much higher levels of noise in the background. Monte-Carlo simulations showed that ¹⁸⁸Re imaging with UHRC is severely affected by down-scattered photons from high-energy emissions. The mouse images showed similar biodistribution of ¹⁸⁸Re-microspheres for both collimators.ConclusionsVECTor/CT provided ¹⁸⁸Re images quantitatively accurate and with quality comparable to ^99mTc. However, due to large penetration of UHRC by high-energy photons, the use of the HE-UHRC for imaging ¹⁸⁸Re in VECTor/CT is recommended.     

3D image-based dosimetry for Yttrium-90 radioembolization of hepatocellular carcinoma: Impact of imaging method on absorbed dose estimates

BackgroundTo improve therapy outcome of Yttrium-90 selective internal radiation therapy (⁹⁰Y SIRT), patient-specific post-therapeutic dosimetry is required. For this purpose, various dosimetric approaches based on different available imaging data have been reported. The aim of this work was to compare post-therapeutic 3D absorbed dose images using Technetium-99m (^99mTc) MAA SPECT/CT, Yttrium-90 (⁹⁰Y) bremsstrahlung (BRS) SPECT/CT, and ⁹⁰Y PET/CT.MethodsTen SIRTs of nine patients with unresectable hepatocellular carcinoma (HCC) were investigated. The ^99mTc SPECT/CT data, obtained from ^99mTc-MAA-based treatment simulation prior to ⁹⁰Y SIRT, were scaled with the administered ⁹⁰Y therapy activity. 3D absorbed dose images were generated by dose kernel convolution with scaled ^99mTc/⁹⁰Y SPECT/CT, ⁹⁰Y BRS SPECT/CT, and ⁹⁰Y PET/CT data of each patient. Absorbed dose estimates in tumor and healthy liver tissue obtained using the two SPECT/CT methods were compared against ⁹⁰Y PET/CT.ResultsThe percentage deviation of tumor absorbed dose estimates from ⁹⁰Y PET/CT values was on average −2 ± 18% for scaled ^99mTc/⁹⁰Y SPECT/CT, whereas estimates from ⁹⁰Y BRS SPECT/CT differed on average by −50 ± 13%. For healthy liver absorbed dose estimates, all three imaging methods revealed comparable values.ConclusionThe quantification capabilities of the imaging data influence ⁹⁰Y SIRT tumor dosimetry, while healthy liver absorbed dose values were comparable for all investigated imaging data. When no ⁹⁰Y PET/CT image data are available, the proposed scaled ^99mTc/⁹⁰Y SPECT/CT dosimetry method was found to be more appropriate for HCC tumor dosimetry than ⁹⁰Y BRS SPECT/CT based dosimetry.     

Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization

Background

Scintillation camera imaging is used for treatment planning and post-treatment dosimetry in liver radioembolization (RE). In yttrium-90 (90Y) RE, scintigraphic images of technetium-99m (99mTc) are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium-166 (166Ho) RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry. The aim of this study is to quantitatively evaluate and compare the imaging characteristics of these three isotopes, in order that imaging protocols can be optimized and RE studies with varying isotopes can be compared.

Methodology/Principal Findings

Phantom experiments were performed in line with NEMA guidelines to assess the spatial resolution, sensitivity, count rate linearity, and contrast recovery of 99mTc, 90Y and 166Ho. In addition, Monte Carlo simulations were performed to obtain detailed information about the history of detected photons. The results showed that the use of a broad energy window and the high-energy collimator gave optimal combination of sensitivity, spatial resolution, and primary photon fraction for 90Y Bremsstrahlung imaging, although differences with the medium-energy collimator were small. For 166Ho, the high-energy collimator also slightly outperformed the medium-energy collimator. In comparison with 99mTc, the image quality of both 90Y and 166Ho is degraded by a lower spatial resolution, a lower sensitivity, and larger scatter and collimator penetration fractions.

Conclusions/Significance

The quantitative evaluation of the scintillation camera characteristics presented in this study helps to optimize acquisition parameters and supports future analysis of clinical comparisons between RE studies.     

The effect of attenuation map,scatter energy window width,and volume of interest on the calibration factor calculation in quantitative 177Lu SPECT imaging: Simulation and phantom study

PurposeThe objective of this study was to evaluate the image degrading factors in quantitative ¹⁷⁷Lu SPECT imaging when using both main gamma photopeak energies.MethodsPhantom measurements with two different vials containing various calibrated activities in air or water were performed to derive a mean calibration factor (CF) for large and small volumes of interest (VOIs). In addition, Monte Carlo simulations were utilized to investigate the effect of scatter energy window width, scatter correction method, such as effective scatter source estimation (ESSE) and triple energy window (TEW), and attenuation map on the quantification of ¹⁷⁷Lu. Results: The measured mean CF using large and small VOIs in water was 4.50 ± 0.80 and 4.80 ± 0.72 cps MBq⁻¹, respectively. Simulations showed a reference CF of 3.3 cps MBq⁻¹ for the water-filled phantom considering all photons excluding scattered events. By using the attenuation map generated for 190 keV photons, the calculated CFs for 113 keV and 208 keV are 10% lower than by using the weighted mean energy of 175 keV for ¹⁷⁷Lu. The calculated CF using the TEW correction was 17% higher than using the ESSE method for a water-filled phantom. However, our findings showed that an appropriate scatter window combination can reduce this difference between TEW and ESSE methods.ConclusionsThe present work implies that choosing a suitable width of scatter energy windows can reduce uncertainties in radioactivity quantification. It is suggested to generate the attenuation map at 113 keV and 208 keV, separately. Furthermore, using small VOIs is suggested in CF calculation.     

Quantitative 177Lu SPECT imaging using advanced correction algorithms in non-reference geometry

Peptide receptor therapy with ¹⁷⁷Lu-labelled somatostatin analogues is a promising tool in the management of patients with inoperable or metastasized neuroendocrine tumours. The aim of this work was to perform accurate activity quantification of ¹⁷⁷Lu in complex anthropomorphic geometry using advanced correction algorithms.Acquisitions were performed on the higher ¹⁷⁷Lu photopeak (208 keV) using a Philips IRIX gamma camera provided with medium-energy collimators. System calibration was performed using a 16 mL Jaszczak sphere surrounded by non-radioactive water. Attenuation correction was performed using μ-maps derived from CT data, while scatter and septal penetration corrections were performed using the transmission-dependent convolution-subtraction method. SPECT acquisitions were finally corrected for dead time and partial volume effects. Image analysis was performed using the commercial QSPECT software.The quantitative SPECT approach was validated on an anthropomorphic phantom provided with a home-made insert simulating a hepatic lesion. Quantitative accuracy was studied using three tumour-to-background activity concentration ratios (6:1, 9:1, 14:1).For all acquisitions, the recovered total activity was within 12% of the calibrated activity both in the background region and in the tumour. Using a 6:1 tumour-to-background ratio the recovered total activity was within 2% in the tumour and within 5% in the background. Partial volume effects, if not properly accounted for, can lead to significant activity underestimations in clinical conditions.In conclusion, accurate activity quantification of ¹⁷⁷Lu can be obtained if activity measurements are performed with equipment traceable to primary standards, advanced correction algorithms are used and acquisitions are performed at the 208 keV photopeak using medium-energy collimators.     

Generation of clinical 177Lu SPECT/CT images based on Monte Carlo simulation with GATE

PurposePatient-specific dosimetry in MRT relies on quantitative imaging, pharmacokinetic assessment and absorbed dose calculation. The DosiTest project was initiated to evaluate the uncertainties associated with each step of the clinical dosimetry workflow through a virtual multicentric clinical trial. This work presents the generation of simulated clinical SPECT datasets based on GATE Monte Carlo modelling with its corresponding experimental CT image, which can subsequently be processed by commercial image workstations.MethodsThis study considers a therapy cycle of 6.85 GBq ¹⁷⁷Lu-labelled DOTATATE derived from an IAEA-Coordinated Research Project (E23005) on “Dosimetry in Radiopharmaceutical therapy for personalised patient treatment”. Patient images were acquired on a GE Infinia-Hawkeye 4 gamma camera using a medium energy (ME) collimator. Simulated SPECT projections were generated based on experimental time points and validated against experimental SPECT projections using flattened profiles and gamma index. The simulated projections were then incorporated into the patient SPECT/CT DICOM envelopes for processing and their reconstruction within a commercial image workstation.ResultsGamma index passing rate (2% − 1 pixel criteria) between 95 and 98% and average gamma between 0.28 and 0.35 among different time points revealed high similarity between simulated and experimental images. Image reconstruction of the simulated projections was successful on HERMES and Xeleris workstations, a major step forward for the initiation of a multicentric virtual clinical dosimetry trial based on simulated SPECT/CT images.ConclusionsRealistic ¹⁷⁷Lu patient SPECT projections were generated in GATE. These modelled datasets will be circulated to different clinical departments to perform dosimetry in order to assess the uncertainties in the entire dosimetric chain.     

GATE Validation of Standard Dual Energy Corrections in Small Animal SPECT-CT

This paper addresses ¹²³I and ¹²⁵I dual isotope SPECT imaging, which can be challenging because of spectrum overlap in the low energy spectrums of these isotopes. We first quantify the contribution of low-energy photons from each isotope using GATE-based Monte Carlo simulations for the MOBY mouse phantom. We then describe and analyze a simple, but effective method that uses the ratio of detected low and high energy ¹²³I activity to separate the mixed low energy ¹²³I and ¹²⁵I activities. Performance is compared with correction methods used in conventional tissue biodistribution techniques. The results indicate that the spectrum overlap effects can be significantly reduced, if not entirely eliminated, when attenuation and scatter is either absent or corrected for using standard methods. In particular, we show that relative activity levels of the two isotopes can be accurately estimated for a wide range of organs and provide quantitative validation that standard methods for spectrum overlap correction provide reasonable estimates for reasonable corrections in small-animal SPECT/CT imaging.     

Validation of irtGPUMCD,a GPU-based Monte Carlo internal dosimetry framework for radionuclide therapy

PurposeMonte Carlo (MC) simulations are highly desirable for dose treatment planning and evaluation in radiation oncology. This is true also in emerging nuclear medicine applications such as internal radiotherapy with radionuclides. The purpose of this study is the validation of irtGPUMCD, a GPU-based MC code for dose calculations in internal radiotherapy.MethodsThe female and male phantoms of the International Commission on Radiological Protection (ICRP 110) were used as benchmarking geometries for this study focused on ¹⁷⁷Lu and including ^99mTc and ¹³¹I. Dose calculations were also conducted for a real patient. For phantoms, twelve anatomical structures were considered as target/source organs. The S-values were evaluated with irtGPUMCD simulations (10⁸ photons), with gamma branching ratios of ICRP 107 publication. The ¹⁷⁷Lu electrons S-values were calculated for source organs only, based on local deposition of dose in irtGPUMCD. The S-value relative difference between irtGPUMCD and IDAC-DOSE were evaluated for all targets/sources considered. A DVHs comparison with GATE was conducted. An exponential track length estimator was introduced in irtGPUMCD to increase computational efficiency.ResultsThe relative S-value differences between irtGPUMCD and IDAC-DOSE were <5% while this comparison with GATE was <1%. The DVHs dosimetric indices comparison between GATE and irtGPUMCD for the patient led to an excellent agreement (<2%). The time required for the simulation of 10⁸ photons was 1.5 min for the female phantom, and one minute for the real patient (<1% uncertainty). These results are promising and let envision the use of irtGPUMCD for internal dosimetry in clinical applications.     

Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

Purpose

Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (⁹⁰Y) and lutetium-177 (¹⁷⁷Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas ⁹⁰Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with ¹⁷⁷Lu. We therefore compared the therapeutic potential of targeting either ⁹⁰Y or ¹⁷⁷Lu to human B-cell lymphoma xenografts in mice.

Methods

Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA) and an ⁹⁰Y- or ¹⁷⁷Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent.

Results

The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for ⁹⁰Y (1.3 Gy/MBq) as for ¹⁷⁷Lu (0.6 Gy/MBq). More importantly, therapy with ⁹⁰Y-DOTA-biotin was dramatically more effective than with ¹⁷⁷Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq ⁹⁰Y, whereas 0% were cured using identical amounts of ¹⁷⁷Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with ⁹⁰Y-PRIT and 0% cured with ¹⁷⁷Lu-PRIT. Toxicities were comparable with both isotopes.

Conclusion

⁹⁰Y was therapeutically superior to ¹⁷⁷Lu for streptavidin-biotin PRIT approaches in these human lymphoma xenograft models.     

Simplified patient-specific renal dosimetry in 177Lu therapy: a proof of concept

PurposeThe aim of this proof-of-concept study is to propose a simplified personalized kidney dosimetry procedure in ¹⁷⁷Lu peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors and metastatic prostate cancer. It relies on a single quantitative SPECT/CT acquisition and multiple radiometric measurements executed with a collimated external probe, properly directed on kidneys.MethodsWe conducted a phantom study involving external count-rate measurements in an abdominal phantom setup filled with activity concentrations of ^99mTc, reproducing patient-relevant organ effective half-lives occurring in ¹⁷⁷Lu PRRT. GATE Monte Carlo (MC) simulations of the experiment, using ^99mTc and ¹⁷⁷Lu as sources, were performed. Furthermore, we tested this method via MC on a clinical case of ¹⁷⁷Lu-DOTATATE PRRT with SPECT/CT images at three time points (2, 20 and 70 hrs), comparing a simplified kidney dosimetry, employing a single SPECT/CT and probe measurements at three time points, with the complete MC dosimetry.ResultsThe experimentally estimated kidney half-life with background subtraction applied was compatible within 3% with the expected value. The MC simulations of the phantom study, both with ^99mTc and ¹⁷⁷Lu, confirmed a similar level of accuracy. Concerning the clinical case, the simplified dosimetric method led to a kidney dose estimation compatible with the complete MC dosimetry within 6%, 12% and 2%, using respectively the SPECT/CT at 2, 20 and 70 hrs.ConclusionsThe proposed simplified procedure provided a satisfactory accuracy and would reduce the imaging required to derive the kidney absorbed dose to a unique quantitative SPECT/CT, with consequent benefits in terms of clinic workflows and patient comfort.     

Comparison of 90Y SIRT predicted and delivered absorbed doses using a PSF conversion method

PurposeThe aims of this study were to develop and apply a method to correct for the differences in partial volume effects of pre-therapy Technetium-99 m (^99mTc)-MAA SPECT and post-therapy Yttrium-90 (⁹⁰Y) bremsstrahlung SPECT imaging in selective internal radiation therapy, and to use this method to improve quantitative comparison of predicted and delivered ⁹⁰Y absorbed doses.MethodsThe spatial resolution of ^99mTc SPECT data was converted to that of ⁹⁰Y SPECT data using a function calculated from ^99mTc and ⁹⁰Y point spread functions. This resolution conversion method (RCM) was first applied to ^99mTc and ⁹⁰Y SPECT phantom data to validate the method, and then to clinical data to assess the power of ^99mTc SPECT imaging to predict the therapeutic absorbed dose.ResultsThe maximum difference between absorbed doses to phantom spheres was 178%. This was reduced to 27% after the RCM was applied.The clinical data demonstrated differences within 38% for mean absorbed doses delivered to the normal liver, which were reduced to 20% after application of the RCM. Analysis of clinical data showed that therapeutic absorbed doses delivered to tumours greater than 100 cm³ were predicted to within 52%, although there were differences of up to 210% for smaller tumours, even after the RCM was applied.ConclusionsThe RCM was successfully verified using phantom data. Analysis of the clinical data established that the ^99mTc pre-therapy imaging was predictive of the ⁹⁰Y absorbed dose to the normal liver to within 20%, but had poor predictability for tumours smaller than 100 cm³.     

Theranostic Studies of Human Sodium Iodide Symporter Imaging and Therapy Using 188Re: A Human Glioma Study in Mice

Objective

To investigate the role of ¹⁸⁸Re in human sodium iodide symporter (hNIS) theranostic gene-mediated human glioma imaging and therapy in model mice.

Methods

The human glioma cell line U87 was transfected with recombinant lentivirus encoding the hNIS gene under the control of cytomegalovirus promoter (U87-hNIS). The uptake and efflux of ¹⁸⁸Re were determined after incubating the cells with ¹⁸⁸Re. ¹⁸⁸Re uptake experiments in the presence of various concentrations of sodium perchlorate were carried out. In vitro cell killing tests with ¹⁸⁸Re were performed. U87-hNIS mediated ¹⁸⁸Re distribution, imaging and therapy in nude mice were also tested.

Results

U87-hNIS cell line was successfully established. The uptake of ¹⁸⁸Re in U87-hNIS cells increased up to 26-fold compared to control cells, but was released rapidly with a half-life of approximately 4 minutes. Sodium perchlorate reduced hNIS-mediated ¹⁸⁸Re uptake to levels of control cell lines. U87-hNIS cells were selectively killed following exposure to ¹⁸⁸Re, with a survival of 21.4%, while control cells had a survival of 92.1%. Unlike in vitro studies, U87-hNIS tumor showed a markedly increased ¹⁸⁸Re retention even 48 hours after ¹⁸⁸Re injection. In the therapy study, there was a significant difference in tumor size between U87-hNIS mice (317±67 mm³) and control mice (861±153 mm³) treated with ¹⁸⁸Re for 4 weeks (P<0.01).

Conclusion

The results indicate that inserting the hNIS gene into U87 cells is sufficient to induce specific ¹⁸⁸Re uptake, which has a cell killing effect both in vitro and in vivo. Moreover, our study, based on the function of hNIS as a theranostic gene allowing noninvasive imaging of hNIS expression by ¹⁸⁸Re scintigraphy, provides detailed characterization of in vivo vector biodistribution and level, localization, essential prerequisites for precise planning and monitoring of clinical gene therapy that aims to individualize gene therapy concept.     

Heterobivalent dual-target probe for targeting GRP and Y1 receptors on tumor cells

Receptor targeting ligands for imaging and/or therapy of cancer are limited by heterogeneity of receptor expression by tumor cells, both inter-patient and intra-patient. It is often more important for imaging agents to identify local and distant spread of disease than it is to identify a specific receptor presence. Two natural hormone peptide receptors, GRPR and Y1, are specifically interesting because expression of GRPR, Y1 or both is up-regulated in most breast cancers. We describe here the design and development of a new heterobivalent peptide ligand, truncated bombesin (t-BBN)/BVD15-DO3A, for dual-targeting of GRPR and Y1, and validation of its dual binding capability. Such a probe should be useful in imaging cells, tissues and tumors that are GRPR and/or Y1 positive and should target radioisotopes, for example, ⁶⁸Ga and/or ¹⁷⁷Lu, to more tumors cells than single GRPR or Y1 targeted probes. A GRP targeting ligand, J-G-Abz4-QWAVGHLM-NH₂ (J-G-Abz4-t-BBN), and an Y1 targeting ligand, INP-K[ε-J-(α-DO3A-ε-DGa)-K]-YRLRY-NH₂([ε-J-(α-DO3A-ε-DGa)-K]-BVD-15), were synthesized and coupled to produce the heterobivalent ligand, t-BBN/BVD15-DO3A. Competitive displacement binding assays using t-BBN/BVD15-DO3A against ¹²⁵I-Tyr⁴-BBN yielded an IC₅₀ value of 18 ± 0.7 nM for GRPR in T-47D cells, a human breast cancer cell line. A similar assay using t-BBN/BVD15-DO3A against porcine ¹²⁵I-NPY showed IC₅₀ values of 80 ± 11 nM for Y1 receptor in MCF7 cells, another human breast cancer cell line. In conclusion, it is possible to construct a single DO3A chelate containing probe that can target both GRPR and Y1 on human tumor cells.     

An overview of radioimmunotherapy

Summary In reviewing the current state of affairs in radioimmunotherapy the paper focuses on the main difficulties thus far encountered and the procedures designed to avoid or circumvent these problems. The long range -emitters⁹⁰Y and¹⁸⁸Re have replaced¹³¹I as the isotopes currently receiving most attention for use in radioimmunotherapy, and a range of new chelators are under investigation for in vivo stability and immunogenicity. Approaches aimed at improving tumour targetting and antigen expression such as two-step pretargetting techniques, tumour necrosis treatment and cytokine pretreatment are summarised. Methods designed to improve host-Mab interactions are outlined and the need to incorporate successful ideas from current cancer therapies is emphasised.     

Cystic Parathyroid Adenomas: An Enigmatic Entity and Role of Tc-99 m Sestamibi Scintigraphy

ObjectiveFunctional cystic lesion of the parathyroid gland is a rare cause of primary hyperparathyroidism (PHPT). They have been postulated to arise from the hemorrhage and cystic degeneration in the parathyroid adenoma (PA). We intended to analyze their scintigraphic and histopathological findings since available literature is sparse.MethodsDual-phase ^{99 m}Tc-sestamibi planar and SPECT/CT scans performed from January 2014 to January 2020 in patients presenting with PHPT were retrospectively analyzed. The clinical, biochemical, and ultrasound features were collected. Planar and SPECT/CT imaging parameters were analyzed. Detailed histopathological analysis, along with post-surgical clinical and biochemical features of the patients who underwent surgery, was reviewed with a mean follow-up of 21.8 ± 20.1 months.ResultsOf the 979 scans analyzed, 10 showed cystic parathyroid lesions (M:F- 3:7, mean age 45.6 ± 15 years, range: 23-66). The predominant presenting features in patients were abdominal pain and renal stone disease, present in 60% of the patients. On planar scintigraphy, 90% of the patients had tracer avid distinct lesions, whereas tracer activity was seen in the solid part of the cystic lesions in all 10 patients on SPECT/CT, with cystic areas showing an attenuation of 23.1 ± 7.6 HU. Eight of these patients underwent surgery, with all showing PA with cystic changes on histopathology. Two of these patients also showed hemorrhage within the cystic spaces.ConclusionHemorrhage within a PA may give rise to cystic parathyroid lesions with PHPT. ^{99 m}Tc-sestamibi scintigraphy with dual-phase imaging and SPECT/CT may help in detecting this rare entity.     

Effect of image registration on 3D absorbed dose calculations in 177Lu-DOTATOC peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with ¹⁷⁷Lu or ⁹⁰Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation.A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of ¹⁷⁷Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code.The similarity analysis demonstrated the superiority of the deformable registrations (p < .001).Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [−19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [−67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL.Image based 3D dosimetry for ¹⁷⁷Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans.     

99mTc thyroid imaging system using multiple imaging plates

A system for taking static thyroid ^99mTc images was devised by using multiple imaging plates (IPs) and a low-energy high resolution collimator. System spatial resolution of the IP systems and the gamma camera was determined by referring to standards set by the National Electrical Manufacturers Association. Sensitivity was represented by using lower detection limits (LDLs). The sensitivity and resolution of IP systems using 16 IP probes connecting two collimators and 9 IPs were determined by using a 20 ml thyroid phantom, and compared with the sensitivity of gamma cameras. The sensitivity of the IP systems increased in proportion to the number of IPs. The sensitivity and resolution of a probe using 6 IPs and a high resolution collimator were equivalent to or superior to the gamma camera for taking static thyroid ^99mTc images. IP systems can be applied clinically as mobile static nuclear imaging devices. The performance of IP systems should be thoroughly investigated for combinations of various collimators and the number of IPs in order to verify their efficacy for imaging all organs.     

Optimal antibody-radionuclide combinations for clinical radioimmunotherapy: a predictive model based on mouse pharmacokinetics

A theoretical comparison was made of radioimmunotherapy (RIT) dosimetry estimates for eight radionuclides (⁹⁰Y,¹⁰⁵Rh, ¹³¹I, ¹⁵³Sm, ¹⁸⁶Re, ¹⁸⁸Re,¹⁹⁸Au, ²¹¹At) conjugated to IgG, F(ab′)₂, and Fab antibody forms. Antibody pharmacokinetics, derived from a nude mouse animal model were combined with appropriate physical data and S values to evaluate absorbed dose to a 0.5 kg centrally located tumor, total body and kidney. Radioimmunoconjugates of F(ab′)₂ with ⁹⁰Y, ¹⁵³Sm and ¹⁸⁶Re were predicted to be the most promising for RIT.     

Multicellular dosimetric chain for molecular radiotherapy exemplified with dose simulations on 3D cell spheroids

PurposeAbsorbed radiation dose-response relationships are not clear in molecular radiotherapy (MRT). Here, we propose a voxel-based dose calculation system for multicellular dosimetry in MRT. We applied confocal microscope images of a spherical cell aggregate i.e. a spheroid, to examine the computation of dose distribution within a tissue from the distribution of radiopharmaceuticals.MethodsA confocal microscope Z-stack of a human hepatocellular carcinoma HepG2 spheroid was segmented using a support-vector machine algorithm and a watershed function. Heterogeneity in activity uptake was simulated by selecting a varying amount of the cell nuclei to contain ¹¹¹In, ¹²⁵I, or ¹⁷⁷Lu. Absorbed dose simulations were carried out using vxlPen, a software application based on the Monte Carlo code PENELOPE.ResultsWe developed a schema for radiopharmaceutical dosimetry. The schema utilizes a partially supervised segmentation method for cell-level image data together with a novel main program for voxel-based radiation dose simulations. We observed that for ¹⁷⁷Lu, radiation cross-fire enabled full dose coverage even if the radiopharmaceutical had accumulated to only 60% of the spheroid cells. This effect was not found with ¹¹¹In and ¹²⁵I. Using these Auger/internal conversion electron emitters seemed to guarantee that only the cells with a high enough activity uptake will accumulate a lethal amount of dose, while neighboring cells are spared.ConclusionsWe computed absorbed radiation dose distributions in a 3D-cultured cell spheroid with a novel multicellular dosimetric chain. Combined with pharmacological studies in different tissue models, our cell-level dosimetric calculation method can clarify dose-response relationships for radiopharmaceuticals used in MRT.