Impact of different models based on blood samples and images for bone marrow dosimetry after 177Lu-labeled somatostatin-receptor therapy.

BACKGROUND: Peptide receptor radionuclide therapy with 177Lu-DOTATATE is a recognized option for treating neuroendocrine tumors and has few toxicities, except for the kidneys and bone marrow. The bone marrow dose is generally derived from a SPECT/CT image-based method with four timepoints or from a blood-based method with up to 9 timepoints, but there is still no reference method. This retrospective single-center study on the same cohort of patients compared the calculated bone marrow dose administered with both methods using mono, bi- or tri-exponential models. For the image-based method, the dose was estimated using Planetdose© software. Pearson correlation coefficients were calculated. We also studied the impact of late timepoints for both methods. RESULTS: The bone marrow dose was calculated for 131 treatments with the blood-based method and for 17 with the image-based method. In the former, the median absorbed dose was 15.3, 20.5 and 28.3 mGy/GBq with the mono-, bi- and tri-exponential model, respectively. With the image-based method, the median absorbed dose was 63.9, 41.9 and 60.8 with the mono-, bi- and tri-exponential model, respectively. Blood samples after 24h post-injection did not evidence any change in the absorbed bone marrow dose with the bi-exponential model. On the contrary, the 6-day post-injection timepoint was more informative with the image-based model. CONCLUSION: This study confirms that the estimated bone marrow dose is significantly lower with the blood-based method than with the image-based method. The blood-based method with a bi-exponential model proved particularly useful, without the need for blood samples after 24h post-injection. Nevertheless, this blood-based method is based on an assumption that needs to be more validated. The important difference between the two methods does not allow to determine the optimal one to estimate the true absorbed dose and further studies are necessary to compare with biological effects.

Radiation dose reduction during venous access port implantation: the importance of upgrading equipment and radiation-protection training.

BACKGROUND: Implantable central venous port systems are widely used in oncology. We upgraded our fluoroscopy machines, and all anesthetists completed two training courses focusing on the risks of ionizing radiation for patients and health workers. AIMS: This study aimed to evaluate the impact of upgrading the machines and the radiation-protection training on ionizing radiation exposure during venous port system implantation. METHODS: We retrospectively analyzed consecutive venous port implantations between 2019 and 2022. The older fluoroscopy machines were replaced by two new machines. A first training session about health worker radioprotection was organized. The medical staff completed a second training course focused on protecting patients from ionizing radiation. We defined four distinct time intervals (TI): venous port implantations performed with the old equipment, the new fluoroscopy machines, after the first training course, and after the second training course. The air kerma-area product (KAP) was compared between these four TI and fluoroscopy times and the number of exposures only with the new machines. RESULTS: We analyzed 2587 procedures. A 93% decrease in the median KAP between the first and last TI was noted (median KAP = 323.0 mGy.cm2 vs. 24.0 mGy.cm2, p < 0.0001). A decrease in the KAP was observed for each of the 11 anesthetists. We also noted a significant decrease in the time of fluoroscopy and the number of exposures. CONCLUSIONS: Upgrading the fluoroscopy equipment and completing two dedicated training courses allowed for a drastic decrease patient exposure to ionizing radiation during venous access port implantation by non-radiologist practitioners.

Insertion of synthetic lesions on patient data: a method for evaluating clinical performance differences between PET systems.

BACKGROUND: Performance assessment of positron emission tomography (PET) scanners is crucial to guide clinical practice with efficiency. We have already introduced and experimentally evaluated a simulation method allowing the creation of a controlled ground truth for system performance assessment. In the current study, the goal was to validate the method using patient data and demonstrate its relevance to assess PET performances accuracy in clinical conditions. METHODS: Twenty-four patients were recruited and sorted into two groups according to their body mass index (BMI). They were administered with a single dose of 2 MBq/kg 18F-FDG and scanned using clinical protocols consecutively on two PET systems: the Discovery-IQ (DIQ) and the Discovery-MI (DMI). For each BMI group, sixty synthetic lesions were dispatched in three subgroups and inserted at relevant anatomical locations. Insertion of synthetic lesions (ISL) was performed at the same location into the two consecutive exams. Two nuclear medicine physicians evaluated individually and blindly the images by qualitatively and semi-quantitatively reporting each detected lesion and agreed on a consensus. We assessed the inter-system detection rates of synthetic lesions and compared it to an initial estimate of at least 1.7 more targets detected on the DMI and the detection rates of natural lesions. We determined the inter-reader variability, evaluated according to the inter-observer agreement (IOA). Adequate inter-reader variability was found for IOA above 80%. Differences in standardized uptake value (SUV) metrics were also studied. RESULTS: In the BMI ≤ 25 group, the relative true positive rate (RTPR) for synthetic and natural lesions was 1.79 and 1.83, respectively. In the BMI > 25 group, the RTPR for synthetic and natural lesions was 2.03 and 2.27, respectively. For each BMI group, the detection rate using ISL was consistent to our estimate and with the detection rate measured on natural lesions. IOA above 80% was verified for any scenario. SUV metrics showed a good agreement between synthetic and natural lesions. CONCLUSIONS: ISL proved relevant to evaluate performance differences between PET scanners. Using these synthetically modified clinical images, we can produce a controlled ground truth in a realistic anatomical model and exploit the potential of PET scanner for clinical purposes.

Normal organ dosimetry for thyroid cancer patients treated with radioiodine as part of the multi-centre multi-national Horizon 2020 MEDIRAD project.

PURPOSE: Dosimetry is rarely performed for the treatment of differentiated thyroid cancer patients with Na[131I]I (radioiodine), and information regarding absorbed doses delivered is limited. Collection of dosimetry data in a multi-centre setting requires standardised quantitative imaging and dosimetry. A multi-national, multi-centre clinical study was performed to assess absorbed doses delivered to normal organs for differentiated thyroid cancer patients treated with Na[131I]I. METHODS: Patients were enrolled in four centres and administered fixed activities of 1.1 or 3.7 GBq of Na[131I]I using rhTSH stimulation or under thyroid hormone withdrawal according to local protocols. Patients were imaged using SPECT(/CT) at variable imaging time-points following standardised acquisition and reconstruction protocols. Whole-body retention data were collected. Dosimetry for normal organs was performed at two dosimetry centres and results collated. RESULTS: One hundred and five patients were recruited. Median absorbed doses per unit administered activity of 0.44, 0.14, 0.05 and 0.16 mGy/MBq were determined for the salivary glands of patients treated at centre 1, 2, 3 and 4, respectively. Median whole-body absorbed doses for 1.1 and 3.7 GBq were 0.05 Gy and 0.16 Gy, respectively. Median whole-body absorbed doses per unit administered activity of 0.04, 0.05, 0.04 and 0.04 mGy/MBq were calculated for centre 1, 2, 3 and 4, respectively. CONCLUSIONS: A wide range of normal organ doses were observed for differentiated thyroid cancer patients treated with Na[131I]I, highlighting the necessity for individualised dosimetry. The results show that data may be collated from multiple centres if minimum standards for the acquisition and dosimetry protocols can be achieved.

RadioLigand Therapy with [177Lu]Lu-PSMA-617 for Salivary Gland Cancers: Literature Review and First Compassionate Use in France.

Salivary gland cancers are rare tumors comprising a large group of heterogeneous tumors with variable prognosis. Their therapeutic management at a metastatic stage is challenging due to the lack of therapeutic lines and the toxicity of treatments. [177Lu]Lu-PSMA-617 (prostate-specific membrane antigen) is a vectored radioligand therapy (RLT) initially developed to treat castration-resistant metastatic prostate cancer with encouraging results in terms of efficacy and toxicity. Many malignant cells could be treated with [177Lu]Lu-PSMA-617 as long as they express PSMA as a consequence of androgenic pathway activation. RLT may be used when anti-androgen hormonal treatment has failed, particularly in prostate cancer. [177Lu]Lu-PSMA-617 has been proposed in certain salivary gland cancers, though the expression of PSMA is demonstrated by a significant uptake using [68Ga]Ga-PSMA-11 PET scan. This theranostic approach could be a new therapeutic option, warranting prospective investigation in a larger cohort. We review the literature on this subject and offer a clinical illustration of compassionate use in France as a perspective for administering [177Lu]Lu-PSMA-617 in salivary gland cancer.

Setting up a quantitative SPECT imaging network for a European multi-centre dosimetry study of radioiodine treatment for thyroid cancer as part of the MEDIRAD project.

BACKGROUND: Differentiated thyroid cancer has been treated with radioiodine for almost 80 years, although controversial questions regarding radiation-related risks and the optimisation of treatment regimens remain unresolved. Multi-centre clinical studies are required to ensure recruitment of sufficient patients to achieve the statistical significance required to address these issues. Optimisation and standardisation of data acquisition and processing are necessary to ensure quantitative imaging and patient-specific dosimetry. MATERIAL AND METHODS: A European network of centres able to perform standardised quantitative imaging of radioiodine therapy of thyroid cancer patients was set-up within the EU consortium MEDIRAD. This network will support a concurrent series of clinical studies to determine accurately absorbed doses for thyroid cancer patients treated with radioiodine. Five SPECT(/CT) systems at four European centres were characterised with respect to their system volume sensitivity, recovery coefficients and dead time. RESULTS: System volume sensitivities of the Siemens Intevo systems (crystal thickness 3/8″) ranged from 62.1 to 73.5 cps/MBq. For a GE Discovery 670 (crystal thickness 5/8″) a system volume sensitivity of 92.2 cps/MBq was measured. Recovery coefficients measured on three Siemens Intevo systems show good agreement. For volumes larger than 10 ml, the maximum observed difference between recovery coefficients was found to be ± 0.02. Furthermore, dead-time coefficients measured on two Siemens Intevo systems agreed well with previously published dead-time values. CONCLUSIONS: Results presented here provide additional support for the proposal to use global calibration parameters for cameras of the same make and model. This could potentially facilitate the extension of the imaging network for further dosimetry-based studies.

Evaluation of PET quantitation accuracy among multiple discovery IQ PET/CT systems via NEMA image quality test.

INTRODUCTION: Quantitative imaging biomarkers are becoming usual in oncology for assessing therapy response. The harmonization of image quantitation reporting has become of utmost importance due to the multi-center trials increase. The NEMA image quality test is often considered for the evaluation of quantitation and is more accurate with a radioactive solid phantom that reduces variability. The goal of this project is to determine the level of variability among imaging centers if acquisition and imaging protocol parameters are left to the center's preference while all other parameters are fixed including the scanner type. METHODS: A NEMA-IQ phantom filled with radioactive 68Ge solid resin was imaged in five clinical sites throughout Europe. Sites reconstructed data with OSEM and BSREM algorithms applying the sites' clinical parameters. Images were analyzed according with the NEMA-NU2-2012 standard using the manufacturer-provided NEMA tools to calculate contrast recovery (CR) and background variability (BV) for each sphere and the lung error (LE) estimation. In addition, a 18F-filled NEMA-IQ phantom was also evaluated to obtain a gauge for variability among centers when the sites were provided with identical specific instructions for acquisition and reconstruction protocol (the aggregate of data from 12 additional sites is presented). RESULTS: The data using the 68Ge solid phantom showed no statistical differences among different sites, proving a very good reproducibility among the PET center models even if dispersion of data is higher with OSEM compared to BSREM. Furthermore, BSREM shows better CR and comparable BV, while LE is slightly reduced. Two centers exhibit significant differences in CR and BV values for the 18F NEMA NU2-2012 experiments; these outlier results are explained. CONCLUSION: The same PET system type from the various sites produced similar quantitative results, despite allowing each site to choose their clinical protocols with no restriction on data acquisition and reconstruction parameters. BSREM leads to lower dispersion of quantitative data among different sites. A solid radioactive phantom may be recommended to qualify the sites to perform quantitative imaging.

Gated 18F-FDG PET/CT of the Lung Using a Respiratory Spirometric Gating Device: A Feasibility Study.

Spirometric gating devices (SGDs) can measure the respiratory signal with high temporal resolution and accuracy. The primary objective of this study was to assess the feasibility and tolerance of a gated lung PET/CT acquisition using an SGD. The secondary objective was to compare the technical quality, accuracy, and interoperability of the SGD with that of a standard respiratory gating device, Real-Time Position Management (RPM), based on measurement of vertical thoracoabdominal displacement. Methods: A prospective phase I monocentric clinical study was performed on patients undergoing 18F-FDG PET/CT for assessment of a solitary lung nodule, staging of lung malignancy, or planning of radiotherapy. After whole-body PET/CT, a centered gated acquisition of both PET and CT was simultaneously obtained with the SGD and RPM during normal breathing. Results: Of the 46 patients who were included, 6 were prematurely excluded (1 because of hyperglycemia and 5 because of distant metastases revealed by whole-body PET/CT, leading to an unjustified extra gated acquisition). No serious adverse events were observed. Of the 40 remaining patients, the gated acquisition was prematurely stopped in 1 patient because of mask discomfort (2.5%; confidence interval [CI], 0.1%-13.2%). This event was considered patient tolerance failure. The SGD generated accurately gated PET/CT images, with more than 95% of the breathing cycle detected and high temporal resolution, in 34 of the 39 patients (87.2%; 95% CI, 60.0%-100.0%) and failed to generate a biologic tumor volume in 1 of 21 patients with increased 18F-FDG uptake (4.8%; 95% CI, 0.1%-26.5%). The quality and accuracy of respiratory signal detection and synchronization were significantly better than those obtained with RPM (P < 0.05). Conclusion: This trial supports the use of an SGD for gated lung PET/CT because of its high patient tolerance and accuracy. Although this technique seems to technically outperform RPM for gated PET/CT, further assessment of its superiority and the clinical benefit is warranted. We believe that this technique could be used as a gold standard to develop innovative approaches to eliminate respiration-induced blurring artifacts.

Fluorine-18-fluorocholine PET/CT parameters predictive for hematological toxicity to radium-223 therapy in castrate-resistant prostate cancer patients with bone metastases: a pilot study.

PURPOSE: This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy. PATIENTS AND METHODS: F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra. Bone metastatic disease was quantified on the basis of the maximum standardized uptake value (SUV), total lesion activity (TLA=MBTV×SUVmean), or MBTV/height (MBTV/H) and TLA/H. F-FCH PET/CT bone tumor burden and activity were analyzed to identify which parameters could predict hematological toxicity [on hemoglobin (Hb), platelets (PLTs), and lymphocytes] while on Ra therapy. Pearson's correlation was used to identify the correlations between age, prostate-specific antigen, and F-FCH PET parameters. RESULTS: MBTV ranged from 75 to 1259 cm (median: 392 cm). TLA ranged from 342 to 7198 cm (median: 1853 cm). Patients benefited from two to six cycles of Ra (n=56 cycles in total). At the end of Ra therapy, five of the 15 (33%) patients presented grade 2/3 toxicity on Hb and lymphocytes, whereas three of the 15 (20%) patients presented grade 2/3 PLT toxicity.Age was correlated negatively with both MBTV (r=-0.612, P=0.015) and TLA (r=-0.596, P=0.018). TLA, TLA/H, and MBTV/H predicted hematological toxicity on Hb, whereas TLA/H and MBTV/H predicted toxicity on PLTs at the end of Ra cycles. Receiver operating characteristic curve analysis allowed to define the cutoffs for MBTV (915 cm) and TLA (4198 cm) predictive for PLT toxicity, with an accuracy of 0.92 and 0.99. CONCLUSION: Tumor bone burden calculation is feasible with F-FCH PET/CT with freely available open-source software. In this pilot study, baseline F-FCH PET/CT markers (TLA, MBTV) have shown abilities to predict Hb and PLT toxicity after Ra therapy and could be explored for patient selection and treatment optimization.

A clinical evaluation of the impact of the Bayesian penalized likelihood reconstruction algorithm on PET FDG metrics.

PURPOSE: The aim of this study was to evaluate the impact of using the Bayesian penalized likelihood (BPL) algorithm on a bismuth germanium oxide positron emission tomography (PET)/computed tomography (CT) system for F-FDG PET/CT exams in case of low injected activity and scan duration. MATERIALS AND METHODS: F-FDG respiratory gated PET/CT performed on 102 cancer patients, injected with ∼2 MBq/kg of F-FDG, were reconstructed using two algorithms: ordered subset expectation maximization (OSEM) and BPL. The signal-to-noise ratio (SNR) was calculated as the ratio of mean standard uptake value (SUV) over the standard deviation in a reference volume defined automatically in the liver. The peak SUV and volumes were also measured in lesions larger than 2 cm thanks to the automated segmentation method. RESULTS: On 85 respiratory gated patients, the median SNR was significantly higher with BPL (P<0.0001) and it is even better when the BMI of the patient increases (odds ratio=1.26).For the 55 lesions, BPL significantly increased the SUVpeak [difference: (-0.5; 1.4), median=0.4, P<0.0001] compared with OSEM in 83.6% of the cases. With BPL, the volume was lower in 61.8% of the cases compared with OSEM, but this was not statistically significant. CONCLUSION: The BPL algorithm improves the image quality and lesion contrast and appears to be particularly appropriate for patients with a high BMI as it improves the SNR. However, it will be important for patient follow-up or multicenter studies to use the same algorithm and preferably BPL.

Clinical outcomes 1 year after empiric 131I therapy for hyperthyroid disorders: real life experience and predictive factors of functional response.

Radioiodine is a therapeutic option in Europe for Graves' disease (GD) and toxic multinodular goiter (MNG). PURPOSE: To compare empiric and calculated I activities using 2013 EANM recommendations. To look for predictive factors of therapeutic response to an empiric activity of I. To assess clinical situations favoring calculated treatment modalities. PATIENTS AND METHODS: Prospective monocentric study of clinical outcomes at 1 year follow-up in 86 patients with GD and MNG who received empiric I therapeutic activities (348-939 MBq). Differences between empiric and calculated activities were confronted to clinical outcomes. Physicians were not aware of the calculated activity at the time of prescription. RESULTS: One year after treatment, 9% (5/57) of GD patients and 7% (2/29) of MNG patients were still in a hyperthyroid state. Thyroid volume was reduced by 67% for GD and by 50% for MNG. In GD, empiric I activities were higher than calculated ones (564±131 vs. 316±319 MBq, P<0.001) in 93% (53/57) of patients. Pretherapeutic thyroid volume (>26 ml for GD; >40 ml for MNG) was associated with persistent hyperthyroidism. CONCLUSION: Empirically administered I for GD and MNG was associated with very high efficacy in thyroid function control and no side effects. Thyroid volume reduction did not preclude treatment efficacy. Activity calculation could be a useful method for treating patients with GD and thyroid volumes higher than 26 ml or patients with MNG and thyroid volumes higher than 40 ml. A selective approach based on pretherapeutic thyroid volume and radioiodine biokinetics might improve treatment success.