Dataset Information

Characterisation of a hand-held CZT-based gamma camera for ¹⁷⁷Lu imaging.

ABSTRACT:

Background

Currently, hand-held gamma cameras are being developed for ^99mTc imaging, mainly for sentinel lymph node detection. These cameras offer advantages, such as mobility and ease of access, and may be useful also for other applications such as biokinetic studies in animals or for imaging of small, superficial structures in patients. In this work, the suitability of a CZT-based hand-held camera for ¹⁷⁷Lu imaging is investigated. The energy response of CZT-based detectors combined with the multiple photon emissions of ¹⁷⁷Lu poses new challenges compared to ^99mTc imaging, and a thorough camera characterisation is thus warranted.

Methods

Three collimators (LEHR, LEHS, and MEGP) and three energy windows (55 keV, 113 keV, and 208 keV) are investigated. Characterised camera properties include the system spatial resolution, energy resolution, sensitivity, image uniformity, septal penetration, and temperature dependence. Characterisations are made starting from NEMA guidelines when applicable, with adjustments made when required. The applicability of the camera is demonstrated by imaging of a superficially located tumour in a patient undergoing [¹⁷⁷ Lu]Lu-DOTA-TATE therapy.

Results

Overall, the results are encouraging. Compared to a conventional gamma camera, the hand-held camera generally has a higher sensitivity for a given collimator. For source-collimator distances below 3 cm, the spatial resolution FWHM is within 6 mm for the LEHR and MEGP collimators. Before uniformity correction, the central field-of-view integral uniformity shows best results for the 113-keV window, with values obtained between 11 and 14%. The corresponding values after uniformity correction are within 3%. Effects of septal penetration are observed but are manageable with a proper combination of collimator and energy window setting. Septal penetration and collimator scatter not only affect the 208-keV window but also contribute with counts in lower windows due to energy-tailing effects. The patient study revealed non-uniform uptake patterns in a region that appeared uniform in a conventional gamma camera image.

Conclusions

The results show that the hand-held camera can be used for ¹⁷⁷Lu imaging. A 113-keV energy window combined with LEHR or MEGP collimators provides the best image system characteristics.

SUBMITTER: Roth D

PROVIDER: S-EPMC7343677 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Characterisation of a hand-held CZT-based gamma camera for <sup>177</sup>Lu imaging.

Roth Daniel D Larsson Erik E Sundlöv Anna A Sjögreen Gleisner Katarina K

EJNMMI physics 20200708 1

<h4>Background</h4>Currently, hand-held gamma cameras are being developed for <sup>99m</sup>Tc imaging, mainly for sentinel lymph node detection. These cameras offer advantages, such as mobility and ease of access, and may be useful also for other applications such as biokinetic studies in animals or for imaging of small, superficial structures in patients. In this work, the suitability of a CZT-based hand-held camera for <sup>177</sup>Lu imaging is investigated. The energy response of CZT-based ...[more]

PMID: 32642884

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Project description:BackgroundDosimetry after radiopharmaceutical therapy with 177Lu (177Lu-RPT) relies on quantitative SPECT/CT imaging, for which suitable reconstruction protocols are required. In this study, we characterized for the first time the quantitative performance of a ring-shaped CZT-based camera using two different reconstruction algorithms: an ordered subset expectation maximization (OSEM) and a block sequential regularized expectation maximization (BSREM) combined with noise reduction regularization. This study lays the foundations for the definition of a reconstruction protocol enabling accurate dosimetry for patients treated with 177Lu-RPT.MethodsA series of 177Lu-filled phantoms were acquired on a StarGuide™ (GE HealthCare), with energy and scatter windows centred at 208 (± 6%) keV and 185 (± 5%) keV, respectively. Images were reconstructed with the manufacturer implementations of OSEM (GE-OSEM) and BSREM (Q.Clear) algorithms, and various combinations of iterations and subsets. Additionally, the manufacturer-recommended Q.Clear-based reconstruction protocol was evaluated. Quantification accuracy, measured as the difference between the SPECT-based and the radionuclide calibrator-based activity, and noise were evaluated in a large cylinder. Recovery coefficients (RCs) and spatial resolution were assessed in a NEMA IEC phantom with sphere inserts. The reconstruction protocols considered suitable for clinical applications were tested on a cohort of patients treated with [177Lu]Lu-PSMA-I&T.ResultsThe accuracy of the activity from the cylinder, although affected by septal penetration, was < 10% for all reconstructions. Both algorithms featured improved spatial resolution and higher RCs with increasing updates at the cost of noise build-up, but Q.Clear outperformed GE-OSEM in reducing noise accumulation. When the reconstruction parameters were carefully selected, similar values for noise (~0.15), spatial resolution (~1 cm) and RCs were found, irrespective of the reconstruction algorithm. Analogue results were found in patients.ConclusionsAccurate activity quantification is possible when imaging 177Lu with StarGuide™. However, the impact of septal penetration requires further investigations. GE-OSEM is a valid alternative to the recommended Q.Clear reconstruction algorithm, featuring comparable performances assessed on phantoms and patients.

Project description:Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin receptor (SSTR) analogs is a common approach in advanced neuroendocrine neoplasms. Recently, SSTR antagonists have shown promising results for imaging and therapy due to a higher number of binding sites than in commonly used agonists. We evaluated PRRT with SSTR agonist 177Lu-DOTATOC and antagonist 177Lu-DOTA-JR11 longitudinally in an orthotopic murine pancreatic neuroendocrine neoplasm model expressing human SSTR2. Morphologic and metabolic changes during treatment were assessed using multimodal imaging, including hybrid PET/MRI and SPECT/CT. Methods: In vitro radioligand binding and internalization assays and cell-cycle analysis were performed. SSTR2-transfected BON cells (BON-SSTR2) were used for in vivo experiments. Tumor-bearing mice received 2 intravenous injections of 100 μL of saline, 30 MBq of 177Lu-DOTATOC, or 20 MBq of 177Lu-DOTA-JR11 with an interval of 3 wk. Weekly T2-weighted MRI was performed for tumor monitoring. Viability of the tumor tissue was assessed by 18F-FDG PET/MRI once after PRRT. Tumor and kidney uptake of the respective radiopharmaceuticals was measured 24 h after injection by SPECT/CT. Results: Compared with 177Lu-DOTATOC, 177Lu-DOTA-JR11 treatment resulted in an increased accumulation of cells in G2/M phase. Animals treated with the SSTR antagonist showed a significant reduction in tumor size (P < 0.001) and an increased median survival (207 d; interquartile range [IQR], 132-228) compared with 177Lu-DOTATOC (126 d; IQR, 118-129). SPECT/CT revealed a 4-fold higher median tumor uptake for the antagonist and a 3-fold higher tumor-to-kidney ratio in the first treatment cycle. During the second therapy cycle, tumor uptake of 177Lu-DOTATOC was significantly lower (P = 0.01) whereas 177Lu-DOTA-JR11 uptake remained stable. Imaging of tumor morphology indicated comparatively larger necrotic fractions for 177Lu-DOTA-JR11 despite further tumor growth. These results were confirmed by 18F-FDG PET, revealing the least amount of viable tumor tissue in 177Lu-DOTA-JR11-treated animals, at 6.2% (IQR, 2%-23%). Conclusion: 177Lu-DOTA-JR11 showed a higher tumor-to-kidney ratio and a more pronounced cytotoxic effect than did 177Lu-DOTATOC. Additionally, tumor uptake was more stable over the course of 2 treatment cycles.

Project description:BackgroundRadiohybrid PSMA-targeted ligands (rhPSMA) have been introduced as a novel platform for theranostic applications. Among a variety of rhPSMA-ligands developed for radioligand therapy, two stereoisomers [177Lu]Lu-rhPSMA-10.1 and -10.2 have been synthesized and initially characterized in preclinical experiments with the aim to provide an optimized binding profile to human serum albumin, a reduction of charge, and thus accelerated kidney excretion, and unaffected or even improved tumor uptake. As both isomers showed similar in vitro characteristics and tumor uptake at 24 h post injection in tumor bearing mice and in order to identify the isomer with the most favorable pharmacokinetics for radioligand therapy, we carried out in-depth biodistribution and dosimetry studies in tumor-bearing and healthy mice.ResultsrhPSMA-10.1 and -10.2 were radiolabeled with lutetium-177 according to the established procedures of other DOTA-based PSMA ligands and displayed a high and comparable stability in all buffers and human serum (> 97%, 24 h). Biodistribution studies revealed fast clearance from the blood pool (0.3-0.6%ID/g at 1 h) and other background tissues within 48 h. Distinctive differences were found in the kidneys, where [177Lu]Lu-rhPSMA-10.1 displayed lower initial uptake and faster excretion kinetics compared to [177Lu]Lu-rhPSMA-10.2 expressed by a 1.5-fold and ninefold lower uptake value at 1 h and 24 h in healthy animals, respectively. Tumor uptake was comparable and in the range of 8.6-11.6%ID/g for both isomers over 24 h and was maintained up to 168 h at a level of 2.2 ± 0.8 and 4.1 ± 1.4%ID/g for [177Lu]Lu-rhPSMA-10.1 and [177Lu]Lu-rhPSMA-10.2, respectively.ConclusionOur preclinical data on biodistribution and dosimetry indicate a more favorable profile of [177Lu]Lu-rhPSMA-10.1 compared to [177Lu]Lu-rhPSMA-10.2 for PSMA-targeted radioligand therapy. [177Lu]Lu-rhPSMA-10.1 shows fast kidney clearance kinetics resulting in excellent tumor-to-organ ratios over a therapy relevant time course. Meanwhile, [177Lu]Lu-rhPSMA-10.1 is currently being investigated in clinical phase I/II studies in patients with mCRPC (NCT05413850), in patients with high-risk localized PC (NCT06066437, Nautilus Trial) and after external beam radiotherapy (NCT06105918).

Project description:BackgroundIndividualized dosimetry is recommended for [177Lu]Lu-PSMA radioligand therapy (RLT) which is resource-intensive and protocols are often not optimized. Therefore, a simulation study was performed focusing on the determination of efficient optimal sampling schedules (OSS) for renal and tumour dosimetry by investigating different numbers of time points (TPs).MethodsSampling schedules with 1-4 TPs were investigated. Time-activity curves of the kidneys and two tumour lesions were generated based on a physiologically based pharmacokinetic (PBPK) model and biokinetic data of 13 patients who have undergone [177Lu]Lu-PSMA I&T therapy. Systematic and stochastic noise of different ratios was considered when modelling time-activity data sets. Time-integrated activity coefficients (TIACs) were estimated by simulating the hybrid planar/SPECT method for schedules comprising at least two TPs. TIACs based on one single SPECT/CT measurement were estimated using an approximation for reducing the number of fitted parameters. For each sampling schedule, the root-mean-squared error (RMSE) of the deviations of the simulated TIACs from the ground truths for 1000 replications was used as a measure for accuracy and precision.ResultsAll determined OSS included a late measurement at 192 h p.i., which was necessary for accurate and precise tumour TIACs. OSS with three TPs were identified to be 3-4, 96-100 and 192 h with an additional SPECT/CT measurement at the penultimate TP. Kidney and tumour RMSE of 6.4 to 7.7% and 6.3 to 7.8% were obtained, respectively. Shortening the total time for dosimetry to e.g. 96 h resulted in kidney and tumour RMSE of 6.8 to 8.3% and 9.1 to 11%, respectively. OSS with four TPs showed similar results as with three TPs. Planar images at 4 and 68 h and a SPECT/CT shortly after the 68 h measurement led to kidney and tumour RMSE of 8.4 to 12% and 12 to 16%, respectively. One single SPECT/CT measurement at 52 h yielded good approximations for the kidney TIACs (RMSE of 7.0%), but led to biased tumour TIACs.ConclusionOSS allow improvements in accuracy and precision of renal and tumour dosimetry for [177Lu]Lu-PSMA therapy with potentially less effort. A late TP is important regarding accurate tumour TIACs.

Project description:PurposeCXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [68Ga]Ga-Pentixafor and its therapeutic counterpart [177Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents.MethodsCXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and MGMT promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [68Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4.ResultsTwo large mRNA datasets (N = 284; N = 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients-not directly translatable to [68Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or MGMT status or survival.ConclusionUsing immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [68Ga]Ga-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with [177Lu]Lu-Pentixather in the future.

Dataset Information

Characterisation of a hand-held CZT-based gamma camera for ¹⁷⁷Lu imaging.

Background

Methods

Results

Conclusions

Publications

Characterisation of a hand-held CZT-based gamma camera for <sup>177</sup>Lu imaging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Characterisation of a hand-held CZT-based gamma camera for 177Lu imaging.

Background

Methods

Results

Conclusions

Publications

Characterisation of a hand-held CZT-based gamma camera for <sup>177</sup>Lu imaging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Characterisation of a hand-held CZT-based gamma camera for ¹⁷⁷Lu imaging.