[68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET/MRI vs. Histopathological Images in Prostate Cancer: A New Workflow for Spatial Co-Registration.

This study proposed a new workflow for co-registering prostate PET images from a dual-tracer PET/MRI study with histopathological images of resected prostate specimens. The method aims to establish an accurate correspondence between PET/MRI findings and histology, facilitating a deeper understanding of PET tracer distribution and enabling advanced analyses like radiomics. To achieve this, images derived by three patients who underwent both [68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET/MRI before radical prostatectomy were selected. After surgery, in the resected fresh specimens, fiducial markers visible on both histology and MR images were inserted. An ex vivo MRI of the prostate served as an intermediate step for co-registration between histological specimens and in vivo MRI examinations. The co-registration workflow involved five steps, ensuring alignment between histopathological images and PET/MRI data. The target registration error (TRE) was calculated to assess the precision of the co-registration. Furthermore, the DICE score was computed between the dominant intraprostatic tumor lesions delineated by the pathologist and the nuclear medicine physician. The TRE for the co-registration of histopathology and in vivo images was 1.59 mm, while the DICE score related to the site of increased intraprostatic uptake on [68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET images was 0.54 and 0.75, respectively. This work shows an accurate co-registration method for histopathological and in vivo PET/MRI prostate examinations that allows the quantitative assessment of dual-tracer PET/MRI diagnostic accuracy at a millimetric scale. This approach may unveil radiotracer uptake mechanisms and identify new PET/MRI biomarkers, thus establishing the basis for precision medicine and future analyses, such as radiomics.

Evaluation of a 2D UNet-Based Attenuation Correction Methodology for PET/MR Brain Studies.

Deep learning (DL) strategies applied to magnetic resonance (MR) images in positron emission tomography (PET)/MR can provide synthetic attenuation correction (AC) maps, and consequently PET images, more accurate than segmentation or atlas-registration strategies. As first objective, we aim to investigate the best MR image to be used and the best point of the AC pipeline to insert the synthetic map in. Sixteen patients underwent a 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) and a PET/MR brain study in the same day. PET/CT images were reconstructed with attenuation maps obtained: (1) from CT (reference), (2) from MR with an atlas-based and a segmentation-based method and (3) with a 2D UNet trained on MR image/attenuation map pairs. As for MR, T1-weighted and Zero Time Echo (ZTE) images were considered; as for attenuation maps, CTs and 511 keV low-resolution attenuation maps were assessed. As second objective, we assessed the ability of DL strategies to provide proper AC maps in presence of cranial anatomy alterations due to surgery. Three 11C-methionine (METH) PET/MR studies were considered. PET images were reconstructed with attenuation maps obtained: (1) from diagnostic coregistered CT (reference), (2) from MR with an atlas-based and a segmentation-based method and (3) with 2D UNets trained on the sixteen FDG anatomically normal patients. Only UNets taking ZTE images in input were considered. FDG and METH PET images were quantitatively evaluated. As for anatomically normal FDG patients, UNet AC models generally provide an uptake estimate with lower bias than atlas-based or segmentation-based methods. The intersubject average bias on images corrected with UNet AC maps is always smaller than 1.5%, except for AC maps generated on too coarse grids. The intersubject bias variability is the lowest (always lower than 2%) for UNet AC maps coming from ZTE images, larger for other methods. UNet models working on MR ZTE images and generating synthetic CT or 511 keV low-resolution attenuation maps therefore provide the best results in terms of both accuracy and variability. As for METH anatomically altered patients, DL properly reconstructs anatomical alterations. Quantitative results on PET images confirm those found on anatomically normal FDG patients.

State of the art of radiomic analysis in the clinical management of prostate cancer: A systematic review.

We present the current clinical applications of radiomics in the context of prostate cancer (PCa) management. Several online databases for original articles using a combination of the following keywords: "(radiomic or radiomics) AND (prostate cancer or prostate tumour or prostate tumor or prostate neoplasia)" have been searched. The selected papers have been pooled as focus on (i) PCa detection, (ii) assessing the clinical significance of PCa, (iii) biochemical recurrence prediction, (iv) radiation-therapy outcome prediction and treatment efficacy monitoring, (v) metastases detection, (vi) metastases prediction, (vii) prediction of extra-prostatic extension. Seventy-six studies were included for qualitative analyses. Classifiers powered with radiomic features were able to discriminate between healthy tissue and PCa and between low- and high-risk PCa. However, before radiomics can be proposed for clinical use its methods have to be standardized, and these first encouraging results need to be robustly replicated in large and independent cohorts.

Preliminary Results of an Ongoing Prospective Clinical Trial on the Use of 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in Staging of High-Risk Prostate Cancer Patients.

The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent 68Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing 68Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with 68Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, 68Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by 68Ga-PSMA, and 68Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase.

PET/MRI for Staging the Axilla in Breast Cancer: Current Evidence and the Rationale for SNB vs. PET/MRI Trials.

Axillary surgery in breast cancer (BC) is no longer a therapeutic procedure but has become a purely staging procedure. The progressive improvement in imaging techniques has paved the way to the hypothesis that prognostic information on nodal status deriving from surgery could be obtained with an accurate diagnostic exam. Positron emission tomography/magnetic resonance imaging (PET/MRI) is a relatively new imaging tool and its role in breast cancer patients is still under investigation. We reviewed the available literature on PET/MRI in BC patients. This overview showed that PET/MRI yields a high diagnostic performance for the primary tumor and distant lesions of liver, brain and bone. In particular, the results of PET/MRI in staging the axilla are promising. This provided the rationale for two prospective comparative trials between axillary surgery and PET/MRI that could lead to a further de-escalation of surgical treatment of BC. • SNB vs. PET/MRI 1 trial compares PET/MRI and axillary surgery in staging the axilla of BC patients undergoing primary systemic therapy (PST). • SNB vs. PET/MRI 2 trial compares PET/MRI and sentinel node biopsy (SNB) in staging the axilla of early BC patients who are candidates for upfront surgery. Finally, these ongoing studies will help clarify the role of PET/MRI in BC and establish whether it represents a useful diagnostic tool that could guide, or ideally replace, axillary surgery in the future.

18F-FAZA PET/CT in the Preoperative Evaluation of NSCLC: Comparison with 18F-FDG and Immunohistochemistry.

PURPOSE: To assess the capability of 18F-FAZA PET/CT in identifying intratumoral hypoxic areas in early and locally advanced non-small cell lung cancer (NSCLC) patients and to compare 18FFAZA PET/CT with 18F-FDG PET/CT and histopathological biomarkers and to investigate whether the assessment of tumour to blood (T/B) and tumour to muscle (T/M) ratios provide comparable information regarding the hypoxic fractions of the tumour. MATERIALS AND METHODS: Seven patients with NSCLC were prospectively enrolled (3 men, 4 women; median age: 71 years; range 63-80). All patients underwent to 18F-FDG PET/CT and 18F-FAZA PET/CT before surgery. Maximum standardized uptake value (SUVmax) was used to evaluate 18FFDG PET/CT images, while 18F-FAZA PET/CT images have been interpreted by using tumour-toblood (T/B) and tumour-to-muscle (T/M) ratio. Surgery was performed in all patients; immunohistochemical analysis for hypoxia biomarkers was performed on histologic tumor samples. RESULTS: All lung lesions showed intense 18F-FDG uptake (mean SUVmax: 7.35; range: 2.35-25.20). A faint 18F-FAZA uptake was observed in 6/7 patients (T/B < 1.2) while significant uptake was present in the remaining 1/7 (T/B and T/M=2.24). On both 2 and 4 h imaging after injection, no differences were observed between T/M and T/B (p=0.5), suggesting that both blood and muscle are equivalent in estimating the background activity for image analysis. Immunohisotchemical analysis showed low or absent staining for hypoxia biomarkers in 3 patients (CA-IX and GLUT-1: 0%; HIF-1α: mean 3.3%; range 0-10). Two patients showed staining for HIF-1α of 5%, with CA-IX being 60% and 30%, respectively and GLUT-1 being 30% and 80%, respectively; in 1/7 HIF-1α was 10%, CA-IX was 50% and GLUT-1 was 90%. In one patient a higher percentage of HIF-1α and CA-IX (20% and 70%, respectively) positive cells was present, with GLUT-1 being 30%. CONCLUSIONS: To the best of our knowledge, this is the first paper assessing hypoxia and glucose metabolism in comparison with immunohistochemistry in patients candidate to surgery for NSCLC. Although including a small number of patients, useful insight regarding correlation between imaging and immunohistochemistry are reported along with methodological suggestions for clinical practice.

Targeted radionuclide therapy: frontiers in theranostics.

The concept of targeted radionuclide therapy (TRT) relies on the use of injected nuclear medicine as treating agents, targeted at the cellular or molecular level. The growth of the interest in TRT was stimulated by the advances in radionuclide production and labeling as well as by the improvement in the knowledge of appropriate and specific molecular targets. In recent years, different studies on TRT were focused on the evaluation of radionuclide compounds able to combine imaging of the disease with TRT, in a theranostic approach. This approach is of particular interest towards the personalization of treatments, allowing both the baseline characterization of oncological pathologies and treatment optimization by correct dosimetric calculation as well as therapy monitoring. This paper presents a review of recent literature on TRT, with a particular focus on clinical applications promoting such a theranostic approach, showing the impact of the synergy of diagnostic imaging and therapeutics.

First Evaluation of PET-Based Human Biodistribution and Dosimetry of 18F-FAZA, a Tracer for Imaging Tumor Hypoxia.

18F-labeled fluoroazomycinarabinoside (18F-FAZA) is a PET biomarker for noninvasive identification of regional tumor hypoxia. The aim of the present phase I study was to evaluate the biodistribution and dosimetry of 18F-FAZA in non-small cell lung cancer patients. Methods: Five patients awaiting surgical resection of histologically proven or radiologically suspected non-small cell lung cancer were prospectively enrolled in the study. The patients underwent PET/CT after injection of 371 ± 32 MBq of 18F-FAZA. The protocol consisted of a 10-min dynamic acquisition of the heart to calculate the activity in blood, followed by 4 whole-body PET/CT scans, from the vertex to the mid thigh, at 10, 60, 120, and 240 min after injection. Urine samples were collected after each imaging session and at 360 min after injection. Volumes of interest were drawn around visually identifiable source organs to generate time-activity curves. Residence times were determined from time-activity curves, and effective doses to individual organs and the whole body were calculated using OLINDA/EXM 1.2 for the standard male and female phantoms. Results: Blood clearance was characterized by a rapid distribution followed by first-order elimination. The highest uptake was in muscle and liver, with respective percentage injected activity (%IA) peaks of 42.7 ± 5.3 %IA and 5.5 ± 0.6 %IA. The total urinary excretion was 15 %IA. The critical organ, with the highest absorbed radiation doses, was the urinary bladder wall, at 0.047 ± 0.008 and 0.067 ± 0.007 mGy/MBq for the 2- and 4-h voiding intervals, respectively. The effective doses for the standard male and female phantoms were 0.013 ± 0.004 and 0.014 ± 0.004 mSv/MBq, respectively, depending on the voiding schedule. Conclusion: With respect to the available literature, the biodistribution of 18F-FAZA in humans appeared to be slightly different from that in mice, with a low clearance in humans. Therefore, use of animal data may moderately underestimate radiation doses to organs in humans. Our dosimetry data showed that a 370-MBq injection of 18F-FAZA is safe for clinical use, similar to other widely used PET ligands. In particular, the effective dose is not appreciably different from those obtained with other hypoxia tracers, such as 18F-fluoromisonidazole.

Differences in polar-map patterns using the novel technologies for myocardial perfusion imaging.

BACKGROUND: New technologies are available in MPI. Our aim was to evaluate their impact on the uniformity of normal myocardial uptake in the polar-map representation, over different count statistics, with and without the attenuation (AC) and scatter corrections (SC). METHODS: A phantom study was performed using 5 Anger gamma cameras with filtered back projection or iterative reconstruction with resolution recovery (IRR), with or without SCAC; a D530c, with or without AC; and a D-SPECT. Count statistics ranged up to a quarter of the reference for the conventional gamma cameras and up to one half for the advanced scanners. Using polar maps, the segmental uptakes and their uncertainties, the 'global uniformity' of polar maps expressed as the coefficient of variation (COV) among the segmental uptakes and the anterior/inferior (ANT/INF) ratio were calculated. RESULTS: Both segmental uptakes and their uncertainties did not depend on the count statistics in the range studied. An increase in the segmental uptakes was found from IRR to IRR + SCAC (78.0% ± 13.5% vs 86.1% ± 9.4%; P < .0001). COV was lower for D-SPECT (10.1% ± 0.5%) and after SCAC for both conventional (9.9% ± 3.0%) and advanced systems (8.9% ± 1.7%). The ANT/INF ratio was above 1 for IRR (1.12 ± 0.07) and fell slightly below 1 for IRR + SCAC (0.97 ± 0.05). CONCLUSIONS: To compare data from the analysis of polar maps across different systems will require the adoption of specific normality databases, developed for each system and reconstruction method employed.

Comparative analysis of cadmium-zincum-telluride cameras dedicated to myocardial perfusion SPECT: A phantom study.

BACKGROUND: This investigation used image data generated by an anthropomorphic phantom with a cardiac insert for a comparison between two solid state cameras: D-SPECT and D530c. METHODS: For each camera, two sets (with and without a simulated transmural defect (TD)) of scans were acquired starting from the in vivo standard count statistics in the left ventricle (LV). Other two acquisitions corresponding to 150% and 50% of the reference count statistics were acquired. Five performance indices related to spatial resolution, contrast, and contrast-to-noise ratio (CNR) were analyzed. RESULTS: D-SPECT showed a lower LV wall thickness and an inferior sharpness than D530c. No significant differences were found in terms of contrast between LV wall and the inner cavity, TD contrast or CNR. No significant differences were observed in CNR when moving from the reference level of count statistics down to 50% or up to 150% of the counts acquired on the LV. CONCLUSIONS: Our results show that D-SPECT and D530c have different performances. The lack of differences in the image performance indices along the range of count statistics explored, indicates that there is the possibility for a further reduction in the injected activity and/or the acquisition time, for both systems.

Automated production of copper radioisotopes and preparation of high specific activity [(64)Cu]Cu-ATSM for PET studies.

(60)Cu and (64)Cu are useful radioisotopes for positron emission tomography (PET) radiopharmaceuticals and may be used for the preparation of promising agents for diagnosis and radiotherapy. In this study, the production and purification of (60/64)Cu starting from (60/64)Ni using a new automated system, namely Alceo, is described. A dynamic process for electrodeposition and dissolution of (60/64)Ni/(60/64)Cu was developed. Preliminary production yields of (60)Cu and (64)Cu were 400 and 300mCi, respectively. (64)Cu was used to radiolabel the hypoxia detection tracer ATSM with a specific activity of 2.2+/-1.3Ci/micromol.

Intake risk and dose evaluation methods for workers in radiochemistry labs of a medical cyclotron facility.

The aim of this paper is to evaluate the risks and doses for the internal contamination of the radiochemistry staff in a high workload medical cyclotron facility. The doses from internal contamination derive from the inhalation of radioactive gas leakage from the cells by personnel involved in the synthesis processes and are calculated from urine sample measurements. Various models are considered for the calculation of the effective committed dose from the analysis of these urine samples, and the results are compared with data obtained from local environmental measurement of the radioactivity released inside the lab.

Performance evaluation of the new whole-body PET/CT scanner: Discovery ST.

Characterisation of the physical performance of the new integrated PET/CT system Discovery ST (GE Medical Systems) has been performed following the NEMA NU 2-1994 (N-94) and the NEMA NU 2-2001 (N-01) standards in both 2D and 3D acquisition configuration. The Discovery ST combines a four or eight multi-slice helical CT scanner with a PET tomograph which consists of 10,080 BGO crystals arranged in 24 rings. The crystal dimensions are 6.3 x 6.3 x 30 mm(3) and they are organised in blocks of 6 x 6 crystals, coupled to a single photomultiplier tube with four anodes. The 24 rings of the PET system allow 47 images to be obtained, spaced by 3.27 mm, and covering an axial field of view of 157 mm. The low- and high-energy thresholds are set to 375 and 650 keV, respectively. The coincidence time window is set to 11.7 ns. Using the NEMA N-94 standard, the main results were: (1) the average (radial and tangential) transverse spatial resolution (FWHM) at 1, 10 and 20 cm off axis was 6.28 mm, 7.09 mm and 7.45 mm in 2D, and 6.68 mm, 7.72 mm and 8.13 mm in 3D; (2) the sensitivity for true events was 8,567 cps/kBq/cc in 2D and 36,649 cps/kBq/cc in 3D; (3) the scatter fraction was 15% in 2D and 30% in 3D; (4) the peak true events rate, the true events rate at 50% of the system dead-time and the true events rate when equal to the random events rate were 750 kcps at 189.81 kBq/cc, 744 kcps at 186.48 kBq/cc and 686 kcps at 150.59 kBq/cc, respectively, in 2D, and 922 kcps at 44.03 kBq/cc, 834 kcps at 53.28 kBq/cc and 921 kcps at 44.03 kBq/cc in 3D; (5) the noise equivalent count (NEC) peak rate was 270 kcps at 34.38 kBq/cc in 3D, with random coincidences estimated by delayed events. Using the NEMA N-01 standards the main results were: (1) the average transverse and axial spatial resolution (FWHM) at 1 cm and 10 cm off axis was 6.28 (4.56) mm and 6.88 (6.11) mm in 2D, and 6.29 (5.68) mm and 6.82 (6.05) mm in 3D; (2) the average sensitivity for the two radial positions (r=0 cm and r=10 cm) was 1.93 cps/kBq in 2D and 9.12 cps/kBq in 3D; (3) the scatter fraction was 19% in 2D and 45% in 3D; (4) the NEC peak rate was 54 kcps at 46.99 kBq/cc in 2D and 45.5 kcps at 10.84 kBq/cc in 3D, when random coincidences were estimated by using k=2 in the NEC formula, while the NEC peak rate was 81 kcps at 64.43 kBq/cc and 66 kcps at 14.86 kBq/cc in 2D and 3D, respectively, when random coincidences were estimated by using k=1 in the NEC formula. The new integrated PET-CT system Discovery ST has good overall performances in both 2D and 3D, with in particular a high sensitivity and a very good 3D NEC response.