Reaching the target dose with one single 131 I-mIBG administration in high-risk neuroblastoma: The determinant impact of the primary tumour.

BACKGROUND: 131 I-metaiodobenzylguanidine (131 I-mIBG) effectiveness in children with metastasised neuroblastoma (NB) is linked to the effective dose absorbed by the target; a target of 4 Gy whole-body dose threshold has been proposed. Achieving this dose often requires administering 131 I-mIBG twice back-to-back, which may cause haematological toxicity. In this study, we tried identifying the factors predicting the achievement of 4 Gy whole-body dose with a single radiopharmaceutical administration. MATERIALS AND METHODS: Children affected by metastatic NB and treated with a high 131 I-mIBG activity (>450 MBq (megabecquerel)/kg) were evaluated retrospectively. Kinetics measurements were carried out at multiple time points to estimate the whole-body dose, which was compared with clinical and activity-related parameters. RESULTS: Seventeen children (12 females, median age 3 years, age range: 1.5-6.9 years) were included. Eleven of them still bore the primary tumour. The median whole-body dose was 2.88 Gy (range: 1.63-4.22 Gy). Children with a 'bulky' primary (>30 mL) received a higher whole-body dose than those with smaller or surgically removed primaries (3.42 ± 0.74 vs. 2.48 ± 0.65 Gy, respectively, p = .016). Conversely, the correlation between activity/kg and the whole-body dose was moderate (R: 0.42, p = .093). In the multivariate analysis, the volume of the primary tumour was the most relevant predictor of the whole-body dose (p = .002). CONCLUSIONS: These data suggest that the presence of a bulky primary tumour can significantly prolong the 131 I-mIBG biological half-life, effectively increasing the absorbed whole-body dose. This information could be used to model the administered activity, allowing to attain the target dose without needing a two-step radiopharmaceutical administration.

[18F]F-Choline PET/CT and 4D-CT in the evaluation of primary hyperparathyroidism: rivals or allies?

Primary hyperparathyroidism is a hard-to-diagnose condition that can run without symptoms for many years without causing symptoms; yet, it can cause dire long-term consequences, such as osteoporosis and renal impairment. First-line diagnostic methods include ultrasound and parathyroid scintigraphy, which provide unsatisfactory results in terms of detection rate. Second-line imaging methods include [18F]F-Choline PET/CT, 4D-CT, and their combination. These methods have shown a great detection rate and sensitivity; however, they are to this day less widespread than the first-line ones. Both the two methods (PET and 4D-CT) have their specific advantages and field of application, as well as their specific limitations. In this narrative review, we will describe the advantages and disadvantages of the two techniques extensively. Moreover, we will try to identify whether the combined examination can play a role and how relevant this role is. Finally, we will try to define the specific clinical situation in which each method can provide the best contribution to diagnosing parathyroid tissue hyperfunction.

Diagnostic and Dosimetry Features of [64Cu]CuCl2 in High-Grade Paediatric Infiltrative Gliomas.

PURPOSE OF THE REPORT: Paediatric diffuse high-grade gliomas (PDHGG) are rare central nervous system neoplasms lacking effective therapeutic options. Molecular imaging of tumour metabolism might identify novel diagnostic/therapeutic targets. In this study, we evaluated the distribution and the dosimetry aspects of [64Cu]CuCl2 in PDHGG subjects, as copper is a key element in cellular metabolism whose turnover may be increased in tumour cells. MATERIAL AND METHODS: Paediatric patients with PDHGG were prospectively recruited. [64Cu]CuCl2 PET/CT was performed 1 h after tracer injection; if the scan was positive, it was repeated 24 and 72 h later. Lesion standardised uptake value (SUV) and target-to-background ratio (TBR) were calculated. Tumour and organ dosimetry were computed using the MIRD algorithm. Each patient underwent an MRI scan, including FLAIR, T2-weighted and post-contrast T1-weighted imaging. RESULTS: Ten patients were enrolled (median age 9, range 6-16 years, 6 females). Diagnoses were diffuse midline gliomas (n = 8, 5 of which with H3K27 alterations) and diffuse hemispheric gliomas (n = 2). Six patients had visible tracer uptake (SUV: 1.0 ± 0.6 TBR: 5 ± 3.1). [64Cu]CuCl2 accumulation was always concordant with MRI contrast enhancement and was higher in the presence of radiological signs of necrosis. SUV and TBR progressively increased on the 24- and 72-h acquisitions (p < 0.05 and p < 0.01, respectively). The liver and the abdominal organs received the highest non-target dose. CONCLUSIONS: [64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood-brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. These characteristics could deserve further analysis, to determine whether this radiopharmaceutical might have a possible therapeutic role as well.

The role of the deep convolutional neural network as an aid to interpreting brain [18F]DOPA PET/CT in the diagnosis of Parkinson's disease.

OBJECTIVES: To test the performance of a 3D convolutional neural network (CNN) in analysing brain [18F]DOPA PET/CT in order to identify patients with nigro-striatal neurodegeneration. We evaluated the robustness of the 3D CNN by testing it against a manual regional analysis of the striata by using a striatal-to-occipital ratio (SOR). METHODS: We analyzed patients who had undergone [18F]DOPA PET/CT from 2016 to 2018. Two examiners interpreted PET/CT images as positive or negative. Only patients with at least 2 years of follow-up and an ascertained neurological diagnosis were included. A 3D CNN was developed to evaluate [18F]DOPA PET/CT and refine the diagnosis of movement disorder. This system required training and testing, which were carried out on 2/3 and 1/3 of patients, respectively. A regional analysis was also conducted by drawing region of interest on T1-weighted 3D MRI scans, on which the [18F]DOPA PET images were first co-registered. RESULTS: Ninety-eight patients were enrolled: 43 presented nigro-striatal degeneration and 55 negative cases used as controls. After training on 69 patients, the diagnostic performance of the 3D CNN was then calculated in 29 patients. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 100%, 89%, 100%, 85% and 93%, respectively. When we compared the 3D CNN results with the SOR analysis, we found that the two patients falsely classified as positive by the 3D CNN procedure showed SOR values ≤ 5th percentile of the negative cases' distribution. CONCLUSIONS: 3D CNNs are able to interpret [18F]DOPA PET/CT properly, revealing patients affected by Parkinson's disease. KEY POINTS: • [18F]DOPA PET/CT is a sensitive diagnostic tool to identify patients with nigro-striatal neurodegeneration. • A semiquantitative evaluation of the images allows a more confident interpretation of the PET findings. • 3D convolutional neural network allows an accurate interpretation of 18F-DOPA PET/CT images, revealing patients affected by Parkinson's disease.

Radioiodine therapy of Graves' disease.

Graves' disease (GD), the most common cause of hyperthyroidism, is an autoimmune disease directly caused by circulating autoantibodies that bind and activate the TSH receptor, inducing metabolic activation of the thyroid gland; this may be associated with important cardiac (atrial fibrillation) and ocular (ophthalmopathy) complications. Treating GD with real curative intent implies the full elimination of the functioning thyroid parenchyma using surgery or radioactive iodine therapy (RAI). RAI has been used in humans with hyperthyroidism since 1941, thanks to the pioneering work of a physician (Dr. Saul Hertz) and a physicist (Dr. Arthur Roberts). The rationale of RAI is based on the effect of radiation of 131I on target cells leading to DNA damage, both directly, through breakage of molecular bonds, and indirectly through the formation of free radicals. In particular, irradiation causes a broad spectrum of cellular damage due to the production of reactive oxygen species and lipid peroxidation of the plasma membrane. Thus, RAI-related cellular death takes place through both apoptosis and necrosis. The aim of this review was to summarize indications, efficacy, safety profile, and dosimetric aspects of RAI treatment in patients affected by GD.

Copper, PET/CT and prostate cancer: a systematic review of the literature.

Copper is an essential element that plays an important role in both cancer development and growth. Indeed, high levels of copper have been found in prostate cancer (PCa), and this finding have paved the way for the use of this element as a target for positron emission tomography (PET) imaging. Copper64 (64Cu) can be used alone, as 64CuCl2, and also as a precursor for the in-vitro radio-labelling of specific carriers for PET imaging in PCa, (e.g. associated to prostate-specific membrane antigen: PSMA). The use of 64Cu-PSMA can yield late acquisitions in which PET images are characterized by a higher target-to-background ratio. At the same time, the shorter positron range of 64Cu provides high spatial resolution, which leads to better detection of small lesions. In this context, the aim of this review was to systematically review studies evaluating the identification of PCa in humans by means of 64CuCl2 and other PET tracers radio-labelled with 64Cu.

Biokinetic and dosimetric aspects of 64CuCl2 in human prostate cancer: possible theranostic implications.

BACKGROUND: The aim of the present study is to evaluate the kinetics and dosimetry of 64CuCl2 in human prostate cancer (PCa) lesions. We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external beam radiation therapy. All patients underwent 64CuCl2-PET/CT to detect PCa recurrence/metastases. Volumes of interest were manually drawn for each 64CuCl2 avid PCa lesion with a diameter > 1 cm on mpMRI in each patient. Time-activity curves for all lesions were obtained. The effective and biological half-life and the standard uptake values (SUVs) were calculated. Tumour/background ratio (TBR) curves as a function of time were considered. Finally, the absorbed dose per lesion was estimated. RESULTS: The mean effective half-life of 64CuCl2 calculated in the lymph nodes (10.2 ± 1.7 h) was significantly higher than in local relapses (8.8 ± 1.1 h) and similar to that seen in bone metastases (9.0 ± 0.4 h). The mean 64CuCl2 SUVmax calculated 1 h after tracer injection was significantly higher in the lymph nodes (6.8 ± 4.3) and bone metastases (6.8 ± 2.9) than in local relapses (4.7 ± 2.4). TBR mean curve of 64CuCl2 revealed that the calculated TBRmax value was 5.0, 7.0, and 6.2 in local relapse and lymph node and bone metastases, respectively, and it was achieved about 1 h after 64CuCl2 injection. The mean absorbed dose of the PCa lesions per administrated activity was 6.00E-2 ± 4.74E-2mGy/MBq. Indeed, for an administered activity of 3.7 GBq, the mean dose absorbed by the lesion would be 0.22 Gy. CONCLUSIONS: Dosimetry showed that the dose absorbed by PCa recurrences/metastases per administrated activity was low. The dosimetric study performed does not take into account the possible therapeutic effect of the Auger electrons. Clinical trials are needed to evaluate 64Cu internalization in the cell nucleus that seems related to the therapeutic effectiveness reported in preclinical studies.

64CuCl2 PET/CT in Prostate Cancer Relapse.

Our objective was to evaluate the biodistribution, kinetics, and radiation dosimetry of 64CuCl2 in humans and to assess the ability of 64CuCl2 PET/CT to detect prostate cancer (PCa) recurrence in patients with biochemical relapse. Methods: We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external-beam radiation therapy. All patients underwent 64CuCl2 PET/CT, 18F-choline PET/CT, and multiparametric MRI within 15 d of each other. Experienced readers interpreted the images, and the detection rate (DR) of each imaging modality was calculated. Histopathology, when available; clinical or laboratory response; and multidisciplinary follow-up were used to confirm the site of disease. In parallel, biodistribution, kinetics of the lesions, and radiation dosimetry of 64CuCl2 were evaluated. Results: From a dosimetric point of view, an administered dose of 200 MBq for 64CuCl2 translated into a 5.7-mSv effective dose. Unlike 18F-choline, 64CuCl2 was not excreted or accumulated in the urinary tract, thus allowing thorough pelvic exploration. The maximum 64CuCl2 uptake at the sites of PCa relapse was observed 1 h after tracer injection. In our cohort, 64CuCl2 PET/CT proved positive in 41 of 50 patients, with an overall DR of 82%. The DRs of 18F-choline PET/CT and multiparametric MRI were 56% and 74%, respectively. The difference between the DRs of 64CuCl2 PET/CT and 18F-choline PET/CT was statistically significant (P < 0.001). Interestingly, on considering prostate-specific antigen (PSA) value, 64CuCl2 PET/CT had a higher DR than 18F-choline PET/CT in patients with a PSA of less than 1 ng/mL. Conclusion: The biodistribution of 64CuCl2 is more suitable than that of 18F-choline for exploring the pelvis and prostatic bed. The 64CuCl2 effective dose is like those of other established PET tracers. In patients with biochemical relapse and a low PSA level, 64CuCl2 PET/CT shows a significantly higher DR than 18F-choline PET/CT.

64Cu-PSMA-617 PET/CT Imaging of Prostate Adenocarcinoma: First In-Human Studies.

AIM: The prostate-specific membrane antigen (PSMA) is a cell surface protein, which is overexpressed in nearly all cases of prostate cancer (PCa). PET imaging with 68Ga-PSMA-HBED-CC has recently found widespread application in the diagnosis of recurrent PCa. In this study, the diagnostic potential of 64Cu-labeled PSMA ligand (PSMA-617) PET in patients with PCa has been investigated. MATERIALS AND METHODS: The study was conducted simultaneously at two nuclear medicine centers, Austria (Vienna, Center 1) and Germany (Bad Berka, Center 2). The patients (n = 29) included in this study were referred for PET (Center 1, 21 patients) or PET/CT (Center 2, 8 patients) imaging with either a high suspicion of recurrent disease or for possible surgical or PSMA radioligand therapy planning. PET images of the whole body were performed at 1 hour p.i. and additional images of the pelvis at 2 hours p.i. RESULTS: In 23 of 29 patients, at least one focus of pathological tracer uptake suspicious for primary disease in the prostate lobe or recurrent disease was detected. Among healthy organs, the salivary glands, kidneys, and liver showed the highest radiotracer uptake. Lesions suspicious for PCa were detected with excellent contrast as early as 1 hour p.i. with high detection rates even at low prostate-specific antigen (PSA) levels. CONCLUSION: The preliminary results of this study demonstrate the high potential of 64Cu-PSMA ligand PET/CT imaging in patients with recurrent disease and in the primary staging of selected patients with progressive local disease. The acquired PET images showed an excellent resolution of the detected lesions with very high lesion-to- background contrast. Furthermore, the long half-life of 64Cu allows distribution of the tracer to clinical PET centers that lack radiochemistry facilities for the preparation of 68Ga-PSMA ligand (satellite concept).

Dosimetric characteristics of electron beams produced by two mobile accelerators, Novac7 and Liac, for intraoperative radiation therapy through Monte Carlo simulation.

The Novac7 and Liac are linear accelerators (linacs) dedicated to intraoperative radiation therapy (IORT), which produce high energy, very high dose-per-pulse electron beams. The characteristics of the accelerators heads of the Novac7 and Liac are different compared to conventional electron accelerators. The aim of this work was to investigate the specific characteristics of the Novac7 and Liac electron beams using the Monte Carlo method. The Monte Carlo code BEAMnrc has been employed to model the head and simulate the electron beams. The Monte Carlo simulation was preliminarily validated by comparing the simulated dose distributions with those measured by means of EBT radiochromic film. Then, the energy spectra, mean energy profiles, fluence profiles, photon contamination, and angular distributions were obtained from the Monte Carlo simulation. The Spencer-Attix water-to-air mass restricted collision stopping power ratios (sw,air) were also calculated. Moreover, the modifications of the percentage depth dose in water (backscatter effect) due to the presence of an attenuator plate composed of a sandwich of a 2 mm aluminum foil and a 4 mm lead foil, commonly used for breast treatments, were evaluated. The calculated sw,air values are in agreement with those tabulated in the IAEA TRS-398 dosimetric code of practice within 0.2% and 0.4% at zref (reference depth in water) for the Novac7 and Liac, respectively. These differences are negligible for practical dosimetry. The attenuator plate is sufficient to completely absorb the electron beam for each energy of the Novac7 and Liac; moreover, the shape of the dose distribution in water strongly changes with the introduction of the attenuator plate. This variation depends on the energy of the beam, and it can give rise to an increase in the maximum dose in the range of 3%-9%.