Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study.

INTRODUCTION: This pilot study evaluated the imaging performance of pretargeted immunological positron emission tomography (immuno-PET) using an anti-carcinoembryonic antigen (CEA) recombinant bispecific monoclonal antibody (BsMAb), TF2 and the [68Ga]Ga-labelled HSG peptide, IMP288, in patients with metastatic colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients requiring diagnostic workup of CRC metastases or in case of elevated CEA for surveillance were prospectively studied. They had to present with elevated CEA serum titre or positive CEA tumour staining by immunohistochemistry of a previous biopsy or surgical specimen. All patients underwent endoscopic ultrasound (EUS), chest-abdominal-pelvic computed tomography (CT), abdominal magnetic resonance imaging (MRI) and positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET). For immuno-PET, patients received intravenously 120 nmol of TF2 followed 30 h later by 150 MBq of [68Ga]Ga-labelled IMP288, both I.V. The gold standard was histology and imaging after 6-month follow-up. RESULTS: Eleven patients were included. No adverse effects were reported after BsMAb and peptide injections. In a per-patient analysis, immuno-PET was positive in 9/11 patients. On a per-lesion analysis, 12 of 14 lesions were positive with immuno-PET. Median SUVmax, MTV and TLG were 7.65 [3.98-13.94, SD 3.37], 8.63 cm3 [1.98-46.64; SD 14.83] and 37.90 cm3 [8.07-127.5; SD 43.47] respectively for immuno-PET lesions. Based on a per-lesion analysis, the sensitivity, specificity, positive-predictive value and negative-predictive value were, respectively, 82%, 25%, 82% and 25% for the combination of EUS/CT/MRI; 76%, 67%, 87% and 33% for FDG-PET; and 88%, 100%, 100% and 67% for immuno-PET. Immuno-PET had an impact on management in 2 patients. CONCLUSION: This pilot study showed that pretargeted immuno-PET using anti-CEA/anti-IMP288 BsMAb and a [68Ga]Ga-labelled hapten was safe and feasible, with promising diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02587247 Registered 27 October 2015.

Assessment of a fully 3D Monte Carlo reconstruction method for preclinical PET with iodine-124.

Iodine-124 is a radionuclide well suited to the labeling of intact monoclonal antibodies. Yet, accurate quantification in preclinical imaging with I-124 is challenging due to the large positron range and a complex decay scheme including high-energy gammas. The aim of this work was to assess the quantitative performance of a fully 3D Monte Carlo (MC) reconstruction for preclinical I-124 PET. The high-resolution small animal PET Inveon (Siemens) was simulated using GATE 6.1. Three system matrices (SM) of different complexity were calculated in addition to a Siddon-based ray tracing approach for comparison purpose. Each system matrix accounted for a more or less complete description of the physics processes both in the scanned object and in the PET scanner. One homogeneous water phantom and three heterogeneous phantoms including water, lungs and bones were simulated, where hot and cold regions were used to assess activity recovery as well as the trade-off between contrast recovery and noise in different regions. The benefit of accounting for scatter, attenuation, positron range and spurious coincidences occurring in the object when calculating the system matrix used to reconstruct I-124 PET images was highlighted. We found that the use of an MC SM including a thorough modelling of the detector response and physical effects in a uniform water-equivalent phantom was efficient to get reasonable quantitative accuracy in homogeneous and heterogeneous phantoms. Modelling the phantom heterogeneities in the SM did not necessarily yield the most accurate estimate of the activity distribution, due to the high variance affecting many SM elements in the most sophisticated SM.

Clinical NECR in 18F-FDG PET scans: optimization of injected activity and variable acquisition time. Relationship with SNR.

The injected activity and the acquisition time per bed position for 18F-FDG PET scans are usually optimized by using metrics obtained from phantom experiments. However, optimal activity and time duration can significantly vary from a phantom set-up and from patient to patient. An approach using a patient-specific noise equivalent count rate (NECR) modelling has been previously proposed for optimizing clinical scanning protocols. We propose using the clinical NECR on a large population as a function of the body mass index (BMI) for deriving the optimal injected activity and acquisition duration per bed position. The relationship between the NEC and the signal-to-noise ratio (SNR) was assessed both in a phantom and in a clinical setting. 491 consecutive patients were retrospectively evaluated and divided into 4 BMI subgroups. Two criteria were used to optimize the injected activity and the time per bed position was adjusted using the NECR value while keeping the total acquisition time constant. Finally, the relationship between NEC and SNR was investigated using an anthropomorphic phantom and a population of 507 other patients. While the first dose regimen suggested a unique injected activity (665 MBq) regardless of the BMI, the second dose regimen proposed a variable activity and a total acquisition time according to the BMI. The NEC improvement was around 35% as compared with the local current injection rule. Variable time per bed position was derived according to BMI and anatomical region. NEC and number of true events were found to be highly correlated with SNR for the phantom set-up and partially confirmed in the patient study for the BMI subgroup under 28 kg m(-2) suggesting that for the scanner, the nonlinear reconstruction algorithm used in this study and BMI < 28 kg m(-2), NEC, or the number of true events linearly correlated with SNR(2).

Monte Carlo simulations of clinical PET and SPECT scans: impact of the input data on the simulated images.

Monte Carlo simulations of emission tomography have proven useful to assist detector design and optimize acquisition and processing protocols. The more realistic the simulations, the more straightforward the extrapolation of conclusions to clinical situations. In emission tomography, accurate numerical models of tomographs have been described and well validated under specific operating conditions (collimator, radionuclide, acquisition parameters, count rates, etc). When using these models under these operating conditions, the realism of simulations mostly depends on the activity distribution used as an input for the simulations. It has been proposed to derive the input activity distribution directly from reconstructed clinical images, so as to properly model the heterogeneity of the activity distribution between and within organs. However, reconstructed patient images include noise and have limited spatial resolution. In this study, we analyse the properties of the simulated images as a function of the properties of the reconstructed images used to define the input activity distributions in (18)F-FDG PET and (131)I SPECT simulations. The propagation through the simulation/reconstruction process of the noise and spatial resolution in the input activity distribution was studied using simulations. We found that the noise properties of the images reconstructed from the simulated data were almost independent of the noise in the input activity distribution. The spatial resolution in the images reconstructed from the simulations was slightly poorer than that in the input activity distribution. However, using high-noise but high-resolution patient images as an input activity distribution yielded reconstructed images that could not be distinguished from clinical images. These findings were confirmed by simulated highly realistic (131)I SPECT and (18)F-FDG PET images from patient data. In conclusion, we demonstrated that (131)I SPECT and (18)F-FDG PET images indistinguishable from real scans can be simulated using activity maps with spatial resolution higher than that used in routine clinical applications.

GATE V6: a major enhancement of the GATE simulation platform enabling modelling of CT and radiotherapy.

GATE (Geant4 Application for Emission Tomography) is a Monte Carlo simulation platform developed by the OpenGATE collaboration since 2001 and first publicly released in 2004. Dedicated to the modelling of planar scintigraphy, single photon emission computed tomography (SPECT) and positron emission tomography (PET) acquisitions, this platform is widely used to assist PET and SPECT research. A recent extension of this platform, released by the OpenGATE collaboration as GATE V6, now also enables modelling of x-ray computed tomography and radiation therapy experiments. This paper presents an overview of the main additions and improvements implemented in GATE since the publication of the initial GATE paper (Jan et al 2004 Phys. Med. Biol. 49 4543-61). This includes new models available in GATE to simulate optical and hadronic processes, novelties in modelling tracer, organ or detector motion, new options for speeding up GATE simulations, examples illustrating the use of GATE V6 in radiotherapy applications and CT simulations, and preliminary results regarding the validation of GATE V6 for radiation therapy applications. Upon completion of extensive validation studies, GATE is expected to become a valuable tool for simulations involving both radiotherapy and imaging.

Implementation of angular response function modeling in SPECT simulations with GATE.

Among Monte Carlo simulation codes in medical imaging, the GATE simulation platform is widely used today given its flexibility and accuracy, despite long run times, which in SPECT simulations are mostly spent in tracking photons through the collimators. In this work, a tabulated model of the collimator/detector response was implemented within the GATE framework to significantly reduce the simulation times in SPECT. This implementation uses the angular response function (ARF) model. The performance of the implemented ARF approach has been compared to standard SPECT GATE simulations in terms of the ARF tables' accuracy, overall SPECT system performance and run times. Considering the simulation of the Siemens Symbia T SPECT system using high-energy collimators, differences of less than 1% were measured between the ARF-based and the standard GATE-based simulations, while considering the same noise level in the projections, acceleration factors of up to 180 were obtained when simulating a planar 364 keV source seen with the same SPECT system. The ARF-based and the standard GATE simulation results also agreed very well when considering a four-head SPECT simulation of a realistic Jaszczak phantom filled with iodine-131, with a resulting acceleration factor of 100. In conclusion, the implementation of an ARF-based model of collimator/detector response for SPECT simulations within GATE significantly reduces the simulation run times without compromising accuracy.

Preoperative localization of parathyroid lesions. Value of 99mTc-MIBI tomography and factors influencing detection.

UNLABELLED: The AIM of our study was to assess retrospectively the value of (99m)Tc-MIBI SPECT in the localization of parathyroid lesions in primary hyperparathyroidism and to determine the impact of PTH level, age, sex, characteristics of the lesions and thyroid nodules on the sensitivity of imaging. PATIENTS, METHODS: Fifty nine patients who were cured after the resection of 60 lesions (50 adenomas, 9 hyperplasias and 1 carcinoma, 9 of them in ectopy) were selected. (99m)TcO(4)(-), early and late (99m)Tc-MIBI planar images (n = 59), (99m)Tc-MIBI SPECT (n = 58) and ultrasound (n = 50) performed preoperatively were analyzed. The imaging results were compared to surgical and histological findings and correlated to different factors suspected of influencing the imaging's sensitivity. RESULTS: Sensitivity of double phase (99m)Tc-MIBI/(99m)TcO(4)(-) scintigraphy was higher than that of early or late scintigraphy alone. SPECT increased the sensitivity of scintigraphy from 85% to 92% and was useful to confirm doubtful foci and to localize ectopic lesions. Ultrasound (US) had the lowest sensitivity (56%) and the highest rate of false-positive results (n = 10), but identified 2 adenomas which were not detected by scintigraphy. Combining all imaging modalities, sensitivity reached 96%. Better sensitivities were observed when age <69 years, preoperative PTH level > or =155 pg/ml, weight of the gland > or =0.80 g and in the absence of thyroid nodules. US was more influenced by these factors than scintigraphy. CONCLUSION: Combination of US, double-phase (99m)Tc-MIBI/(99m)TcO(4)(-) planar scintigraphy and SPECT is the most accurate method for the detection of parathyroid lesions and should be performed before minimally invasive surgery, especially when PTH level is low, in older patients and in cases of multinodular goiter.

Comparison of positron emission tomography and lymphangiography in the diagnosis of infradiaphragmatic Hodgkin's disease.

PURPOSE: To evaluate the respective roles of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) and lymphangiography (LAG) in staging Hodgkin's disease (HD) patients with negative contrast-enhanced infradiaphragmatic computed tomography (CT). MATERIAL AND METHODS: 28 patients underwent FDG-PET and LAG at initial staging. Concordant positive findings on both tests were regarded as actual HD locations and concordant negative findings as true negative. In case of discrepancy, the reference was biopsy or magnetic resonance imaging (MRI). RESULTS: Concordant results were obtained in 26 patients (24 negative, two positive). In two of the 24 negative patients, PET showed additional lesions in the spleen and one celiac lymph node (one patient), and in the right kidney and the right iliac crest (one patient). Discordant results were obtained in two patients. Both methods indicated infradiaphragmatic involvement in different locations in one patient. In the other, PET was falsely positive (PET done within 24 hours after a negative LAG), which was confirmed by biopsy (benign inflammatory, probably due to LAG medium). CONCLUSION: FDG-PET and LAG gave comparable results, making invasive LAG unnecessary. Furthermore, LAG, when performed before PET, can be responsible for false-positive PET results.