Imaging of 212Pb in mice with a clinical SPECT/CT.

INTRODUCTION: 212Pb is a promising radionuclide for targeted alpha therapy. Here, the feasibility of visualising the tumour uptake and biodistribution of 212Pb-NG001 in mice with a clinical SPECT/CT scanner was investigated. METHODS: A mouse phantom with 212Pb was imaged with a clinical- and a preclinical SPECT/CT scanner. Different acquisition and reconstruction settings were investigated on the clinical system (Siemens Symbia Intevo Bold). Two athymic nude mice carrying PC-3 PIP prostate cancer tumours of 235-830 µl received 1.44 MBq of 212Pb-NG001 and were imaged 2, 6, and 24 h post-injection on the clinical SPECT/CT with a Medium Energy collimator and a 40% energy window centred on 79 keV. All acquisition times were 30 min, except the mouse imaging 24 h post-injection which was 60 min. After the final imaging, the organs were harvested and measured on a gamma counter to give an indication of how much activity was present in organs of interest at the last imaging time point. RESULTS: Four volumes in the mouse phantom of ~ 300 µl with 246-303 kBq/ml of 212Pb were distinguishable on images acquired with the clinical SPECT/CT with a high number of reconstruction updates. With the preclinical SPECT, the same volumes were easily distinguished with 49 kBq/ml of 212Pb. Clinical SPECT/CT images of the mice revealed uptake in tumours and bladders 2 h after injection and in tumours containing down to approximately 15 kBq/ml at 6 and 24 h after injection. CONCLUSION: Although the preclinical scanner should be used preferentially in biodistribution studies in mice, the clinical SPECT/CT confirmed uptake in small volumes (e.g. ~ 300 µl volume with ~ 250 kBq/ml). Regardless of system, the resolution and sensitivity limits should be carefully determined, otherwise false negative or too low uptakes can be wrongly interpreted.

Intensifying treatment in PET-positive multiple myeloma patients after upfront autologous stem cell transplantation.

18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET) positivity after first-line treatment with autologous stem cell transplantation (ASCT) in multiple myeloma is strongly correlated with reduced progression-free and overall survival. However, PET-positive patients who achieve PET negativity after treatment seem to have comparable outcomes to patients who were PET negative at diagnosis. Hence, giving PET-positive patients additional treatment may improve their outcome. In this phase II study, we screened first-line patients with very good partial response (VGPR) or better after ASCT with PET. PET-positive patients received four 28-day cycles of carfilzomib-lenalidomide-dexamethasone (KRd). Flow cytometry-based minimal residual disease (MRD) analysis was performed before and after treatment for correlation with PET. Overall, 159 patients were screened with PET. A total of 53 patients (33%) were PET positive and 57% of PET-positive patients were MRD negative, demonstrating that these response assessments are complementary. KRd consolidation converted 33% of PET-positive patients into PET negativity. MRD-negative patients were more likely to convert than MRD-positive patients. In summary, PET after ASCT detected residual disease in a substantial proportion of patients in VGPR or better, even in patients who were MRD negative, and KRd consolidation treatment changed PET status in 33% of patients.

Quantitative SPECT/CT imaging of lead-212: a phantom study.

BACKGROUND: Lead-212 (212Pb) is a promising radionuclide for targeted therapy, as it decays to α-particle emitter bismuth-212 (212Bi) via ß-particle emission. This extends the problematic short half-life of 212Bi. In preparation for upcoming clinical trials with 212Pb, the feasibility of quantitative single photon-emission computed tomography/computed tomography (SPECT/CT) imaging of 212Pb was studied, with the purpose to explore the possibility of individualised patient dosimetric estimation. RESULTS: Both acquisition parameters (combining two different energy windows and two different collimators) and iterative reconstruction parameters (varying the iterations x subsets between 10 × 1, 15 × 1, 30 × 1, 30 × 2, 30 × 3, 30 × 4, and 30 × 30) were investigated to evaluate visual quality and quantitative uncertainties based on phantom images. Calibration factors were determined using a homogeneous phantom and were stable when the total activity imaged exceeded 1 MBq for all the imaging protocols studied, but they increased sharply as the activity decayed below 1 MBq. Both a 20% window centred on 239 keV and a 40% window on 79 keV, with dual scatter windows of 5% and 20%, respectively, could be used. Visual quality at the lowest activity concentrations was improved with the High Energy collimator and the 79 keV energy window. Fractional uncertainty in the activity quantitation, including uncertainties from calibration factors and small volume effects, in spheres of 2.6 ml in the NEMA phantom was 16-21% for all protocols with the 30 × 4 filtered reconstruction except the High Energy collimator with the 239 keV energy window. Quantitative analysis was possible both with and without filters, but the visual quality of the images improved with a filter. CONCLUSIONS: Only minor differences were observed between the imaging protocols which were all determined suitable for quantitative imaging of 212Pb. As uncertainties generally decreased with increasing iterative updates in the reconstruction and recovery curves did not converge with few iterations, a high number of reconstruction updates are recommended for quantitative imaging.

Head and neck paragangliomas in Norway, importance of genetics, updated diagnostic workup and treatment.

BACKGROUND: Head and neck paragangliomas (HNPG) are rare and predominantly benign tumours, originating from the neuroendocrine paraganglionic system. A considerable proportion of HNPGs are hereditary, depending on the population. AIMS/OBJECTIVES: The purpose of this study was to estimate the rate of hereditary HNPGs in a Scandinavian (Norwegian) population, report long-term experience with HNPGs and offer all patients diagnosed an updated follow-up, with emphasis on identifying hereditary HNPGs through genetic screening and multifocality by 18 F-2-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). MATERIAL AND METHODS: Our study was a partly retrospective and partly prospective cohort study. It included patients with HNPG diagnosed at Oslo University Hospital (OUH), Rikshospitalet between 1990 and 2017. The patients underwent genetic testing, 18F-FDG PET/CT and measurement of catecholamines and meta-nephrines in the plasma. All resection specimens and biopsies were subjected to histopathological review. The genetic testing protocol consisted of testing for mutations in the following genes; SDHD, SDHB, SDHC, VHL and RET. RESULTS: Sixty-three patients were included in the study with a median age of 49 years (range 12 - 80). Cranial nerve dysfunction was present upon diagnosis in 13%, and 14% had multifocal paraganglioma (PG) disease. Fifty-six patients (89% of all the patients) underwent genetic testing, and 29% of these had a PG related mutation. Seven of the eight patients (88%) with multifocal PGs who underwent genetic testing had a mutation. In two of the patients, the 18F-FDG PET/CT revealed unknown and subclinical multifocality. CONCLUSIONS AND SIGNIFICANCE: This is the first study with systematic genetic workup and PET/CT imaging in Scandinavia of HNPG patients. The mutation rate was within the lower range reported in the literature with respect to HNPGs. Combining genetic testing and PET/CT imaging in the diagnostic workup of HNPGs is valuable.