Imaging quality of an artificial intelligence denoising algorithm: validation in 68Ga PSMA-11 PET for patients with biochemical recurrence of prostate cancer.

BACKGROUND: 68 Ga-PSMA PET is the leading prostate cancer imaging technique, but the image quality remains noisy and could be further improved using an artificial intelligence-based denoising algorithm. To address this issue, we analyzed the overall quality of reprocessed images compared to standard reconstructions. We also analyzed the diagnostic performances of the different sequences and the impact of the algorithm on lesion intensity and background measures. METHODS: We retrospectively included 30 patients with biochemical recurrence of prostate cancer who had undergone 68 Ga-PSMA-11 PET-CT. We simulated images produced using only a quarter, half, three-quarters, or all of the acquired data material reprocessed using the SubtlePET® denoising algorithm. Three physicians with different levels of experience blindly analyzed every sequence and then used a 5-level Likert scale to assess the series. The binary criterion of lesion detectability was compared between series. We also compared lesion SUV, background uptake, and diagnostic performances of the series (sensitivity, specificity, accuracy). RESULTS: VPFX-derived series were classified differently but better than standard reconstructions (p < 0.001) using half the data. Q.Clear series were not classified differently using half the signal. Some series were noisy but had no significant effect on lesion detectability (p > 0.05). The SubtlePET® algorithm significantly decreased lesion SUV (p < 0.005) and increased liver background (p < 0.005) and had no substantial effect on the diagnostic performance of each reader. CONCLUSION: We show that the SubtlePET® can be used for 68 Ga-PSMA scans using half the signal with similar image quality to Q.Clear series and superior quality to VPFX series. However, it significantly modifies quantitative measurements and should not be used for comparative examinations if standard algorithm is applied during follow-up.

Assessment of 99mTc-NTP 15-5 uptake on cartilage, a new proteoglycan tracer: Study protocol for a phase I trial (CARSPECT).

Background: 99mTc-NTP 15-5 is a SPECT radiotracer targeting proteoglycans (PG), components of the cartilaginous extracellular matrix. Imaging of PGs would be useful for the early detection of cartilage disorders (osteoarthritis, arthritis and chondrosarcoma, Aromatase Inhibitor associated arthralgia (AIA) in breast cancer), and the follow-up of patients under treatment. According to preclinical study results, 99mTc-NTP 15-5, is a good candidate for a specific functional molecular imaging of joints. We intend to initiate a first in-human study to confirm and quantify 99mTc-NTP 15-5 uptake in healthy joints. Methods: As the clinical development of this radiotracer would be oriented toward the functional imaging of joint pathologies, we have chosen to include patients with healthy joints (unilateral osteoarthritis of the knee or breast cancer with indication of AI treatment). This phase I study will be an open-label, multicenter, dose-escalation trial of a radiopharmaceutical orientation to determine the recommended level of activity of 99mTc-NTP 15-5 to obtain the best joint tracer contrasts on images, without dose limiting toxicity (DLT). The secondary objectives will include the study of the pharmacology, biodistribution (using planar whole body and SPECT-CT acquisitions), toxicity, and dosimetry of this radiotracer. The dose escalation with 3 activity levels (5, 10, and 15 MBq/kg), will be conditioned by the absence at the previous level of DLT and of a visualized tracer accumulation on more than 80% of healthy joints as observed on scintigraphy performed at ≤ 2 h post-injection. Discussion: This first in-human phase I trial will be proof-of-concept of the relevance of 99mTc-NTP 15-5 as a cartilage tracer, with the determination of the optimal methodology (dose and acquisition time) to obtain the best contrast to provide a functional image of joints with SPECT-CT. Trial registration number: Clinicaltrials.gov: NCT04481230. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2020-000495-37.

Delayed [ 18 F]-FDG PET Imaging Increases Diagnostic Performance and Reproducibility to Differentiate Recurrence of Brain Metastases From Radionecrosis.

PURPOSE: Differentiating brain metastasis recurrence from radiation necrosis can be challenging during MRI follow-up after stereotactic radiotherapy. [ 18 F]-FDG is the most available PET tracer, but standard images performed 30 to 60 minutes postinjection provide insufficient accuracy. We compared the diagnostic performance and interobserver agreement of [ 18 F]-FDG PET with delayed images (4-5 hours postinjection) with the ones provided by standard and dual-time-point imaging. METHODS: Consecutive patients referred for brain [ 18 F]-FDG PET after inconclusive MRI were retrospectively included between 2015 and 2020 in 3 centers. Two independent nuclear medicine physicians interpreted standard (visually), delayed (visually), and dual-time-point (semiquantitatively) images, respectively. Adjudication was applied in case of discrepancy. The final diagnosis was confirmed histologically or after 6 months of MRI follow-up. Areas under the receiver operating characteristic curves were pairwise compared. RESULTS: Forty-eight lesions from 46 patients were analyzed. Primary tumors were mostly located in the lungs (57%) and breast (23%). The median delay between radiotherapy and PET was 15.7 months. The final diagnosis was tumor recurrence in 24 of 48 lesions (50%), with histological confirmation in 19 of 48 lesions (40%). Delayed images provided a larger area under the receiver operating characteristic curve (0.88; 95% confidence interval [CI], 0.75-0.95) than both standard (0.69; 95% CI, 0.54-0.81; P = 0.0014) and dual-time-point imaging (0.77; 95% CI, 0.63-0.88; P = 0.045), respectively. Interobserver agreement was almost perfect with delayed images ( κ = 0.83), whereas it was moderate with both standard ( κ = 0.48) and dual-time-point images ( κ = 0.61). CONCLUSIONS: [ 18 F]-FDG PET with delayed images is an accurate and reliable alternative to differentiate metastasis recurrence from radiation necrosis in case of inconclusive MRI after brain stereotactic radiotherapy.

Phase I study of [131I] ICF01012, a targeted radionuclide therapy, in metastatic melanoma: MELRIV-1 protocol.

BACKGROUND: Benzamide-based radioligands targeting melanin were first developed for imaging melanoma and then for therapeutic purpose with targeted radionuclide therapy (TRT). [131I]ICF01012 presents a highly favorable pharmacokinetics profile in vivo for therapy. Tumour growth reduction and increase survival have been established in preclinical models of melanoma. According the these preclinical results, we initiate a first-in-human study aimed to determine the recommended dose of [131I]ICF01012 to administer for the treatment of patients with pigmented metastatic melanoma. METHODS: The MELRIV-1 trial is an open-label, multicentric, dose-escalation phase I trial. The study is divided in 2 steps, a selection part with an IV injection of low activity of [131I]ICF01012 (185 MBq at D0) to select patients who might benefit from [131I]ICF01012 TRT in therapeutic part, i.e. patient presenting at least one tumour lesion with [131I]ICF01012 uptake and an acceptable personalized dosimetry to critical organs (liver, kidney, lung and retina). According to dose escalation scheme driven by a Continual Reassessment Method (CRM) design, a single therapeutic injection of 800 MBq/m2, or 1600 MBq/m2, or 2700 MBq/m2 or 4000 MBq/m2 of [131I]ICF01012 will be administered at D11 (± 4 days). The primary endpoint is the recommended therapeutic dose of [131I]ICF01012, with DLT defined as any grade 3-4 NCI-CT toxicity during the 6 weeks following therapeutic dose. Safety, pharmacokinetic, biodistribution (using planar whole body and SPECT-CT acquisitions), sensitivity / specificity of [131I]ICF01012, and therapeutic efficacy will be assessed as secondary objectives. Patients who received therapeutic injection will be followed until 3 months after TRT. Since 6 to 18 patients are needed for the therapeutic part, up to 36 patients will be enrolled in the selection part. DISCUSSION: This study is a first-in-human trial evaluating the [131I]ICF01012 TRT in metastatic malignant melanomas with a diagnostic dose of the [131I]ICF01012 to select the patients who may benefit from a therapeutic dose of [131I]ICF01012, with at least one tumor lesion with [131I]ICF01012 uptake and an acceptable AD to healthy organ. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03784625 . Registered on December 24, 2018. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2016-002444-17.

Decision Tree With Only Two Musculoskeletal Sites to Diagnose Polymyalgia Rheumatica Using [18F]FDG PET-CT.

Introduction: The aim of this study was to find the best ordered combination of two FDG positive musculoskeletal sites with a machine learning algorithm to diagnose polymyalgia rheumatica (PMR) vs. other rheumatisms in a cohort of patients with inflammatory rheumatisms. Methods: This retrospective study included 140 patients who underwent [18F]FDG PET-CT and whose final diagnosis was inflammatory rheumatism. The cohort was randomized, stratified on the final diagnosis into a training and a validation cohort. FDG uptake of 17 musculoskeletal sites was evaluated visually and set positive if uptake was at least equal to that of the liver. A decision tree classifier was trained and validated to find the best combination of two positives sites to diagnose PMR. Diagnosis performances were measured first, for each musculoskeletal site, secondly for combination of two positive sites and thirdly using the decision tree created with machine learning. Results: 55 patients with PMR and 85 patients with other inflammatory rheumatisms were included. Musculoskeletal sites, used either individually or in combination of two, were highly imbalanced to diagnose PMR with a high specificity and a low sensitivity. The machine learning algorithm identified an optimal ordered combination of two sites to diagnose PMR. This required a positive interspinous bursa or, if negative, a positive trochanteric bursa. Following the decision tree, sensitivity and specificity to diagnose PMR were respectively 73.2 and 87.5% in the training cohort and 78.6 and 80.1% in the validation cohort. Conclusion: Ordered combination of two visually positive sites leads to PMR diagnosis with an accurate sensitivity and specificity vs. other rheumatisms in a large cohort of patients with inflammatory rheumatisms.

Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography in Inflammatory Rheumatism, Particularly Polymyalgia Rheumatica: A Retrospective Study of 222 PET/CT.

Purpose: The objective of this study was to evaluate periarticular FDG uptake scores from 18F-FDG-PET/CT to identify polymyalgia rheumatica (PMR) within a population presenting rheumatic diseases. Methods: A French retrospective study from 2011 to 2015 was conducted. Patients who underwent 18F-FDG-PET/CT for diagnosis or follow-up of a rheumatism or an unexplained biological inflammatory syndrome were included. Clinical data and final diagnosis were reviewed. Seventeen periarticular sites were sorted by a visual reading enabling us to calculate two scores: mean FDG visual uptake score, number of sites with significant uptake same as that or higher than liver uptake intensity and by a semi-quantitative analysis using mean maximum standardized uptake value (SUVmax). Optimal cutoffs of visual score and SUVmax to diagnose PMR were determined using receiver operating characteristics curves. Results: Among 222 18F-FDG PET/CT selected for 215 patients, 161 18F-FDG PET/CT were performed in patients who presented inflammatory rheumatism as a final diagnosis (of whom 57 PMR). The presence of at least three sites with significant uptake identified PMR with a sensitivity of 86% and a specificity of 85.5% (AUC 0.872, 95% CI [0.81-0.93]). The mean FDG visual score cutoff to diagnose a PMR was 0.765 with a sensitivity of 82.5% and a specificity of 75.8% (AUC 0.854; 95% CI [0.80-0.91]). The mean SUVmax cutoff to diagnose PMR was 2.168 with a sensitivity of 77.2% and a specificity of 77.6% (AUC 0.842; 95% CI [0.79-0.89]). Conclusions: This study suggests that 18F-FDG PET/CT had good performances to identify PMR within a population presenting rheumatic diseases.

A decrease in brown adipose tissue activity is associated with weight gain during chemotherapy in early breast cancer patients.

BACKGROUND: A decrease in thermogenesis is suspected to be implicated in the energy expenditure reduction during breast cancer treatment. This study aimed to investigate the impact of chemotherapy on the metabolic activity of brown adipose tissue (BAT) and the link with weight variation. METHODS: This was an ancillary analysis of a multicentre trial involving 109 HER2+ breast cancer patients treated with neoadjuvant chemotherapy. A centralised review of 18F-FDG uptake intensity (SUVmax) in specific BAT regions (cervical and supraclavicular) was conducted on two PET-CT scans for each patient (before and after the first course of chemotherapy). RESULTS: Overall, after one course of chemotherapy a significant decrease of 4.4% in 18F-FDG-uptake intensity was observed. It was not correlated to initial BMI, age or season. During chemotherapy, 10.1% (n = 11) of the patients lost weight (- 7.7 kg ± 3.8 kg; ie, - 9.4% ± 3.7%) and 29.4% (n = 32) gained weight (+ 5.1 kg ± 1.7 kg; ie, + 8.5% ± 2.6%). Among these subgroups, only the patients who had gained weight underwent a significant decrease (13.42%) in 18F-FDG uptake intensity (p = 0.042). CONCLUSION: This study is the first to highlight in a large cohort of patients the negative impact of chemotherapy on brown adipose tissue activity. Weight gain during chemotherapy could thus potentially be explained in part by a decrease in brown adipose tissue activity.