PARP-Targeted Radiotheranostics with Auger Electrons: An Updated Overview.

Auger electrons (AEs) represent an intriguing topic in the field of radionuclide therapy. They are emitted by several radionuclides commonly used in nuclear medicine (indium-111, iodine-123, iodine-125), allowing for highly localized energy deposition and thus exerting a radiotoxic effect on specific cellular and sub-cellular targets. However, due to their short range in matter, AEs have had limited use in therapeutic applications so far. In recent years, the synthesis of various radiopharmaceuticals capable of binding to the enzyme poly(ADP-ribose) polymerase 1 has reignited interest in this type of therapy, laying the groundwork for a theranostic approach based on radionuclides emitting AEs. The enzyme PARP-1 operates enzymatically in close proximity to DNA that represents the prime target of radionuclide therapies. Following this trend, several PARP-targeted radiopharmaceuticals for AE-based theranostics have been developed. We provide an updated overview of preclinical studies focused on the applications of this new theranostic approach in glioblastoma, breast, prostate and ovarian carcinoma, and pancreatic adenocarcinoma.

Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study.

PURPOSE: This multicentric study aimed to investigate the main prognostic factors associated with treatment response at 1 year after radioactive iodine therapy (RAIT) and the last disease status in pediatric patients affected by differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: In the period 1990-2020, all consecutive patients ≤ 18 years from six different centers were retrospectively included. Patients were classified as low, intermediate, and high risk for persistence/recurrence. The response to RAIT was evaluated and scored 1 year later according to 2015 ATA guidelines. Moreover, at the last follow-up, the disease status was evaluated and dichotomized as no evidence of disease (NED) or persistent disease. RESULTS: Two hundred and eighty-five patients (197 female, 88 male; mean age 14.4 years) were recruited. All, except nine, underwent near-total thyroidectomy followed by RAIT. One-year after first RAIT, 146/276 (53%) patients had excellent response, 37/276 (14%) indeterminate response, and 91/276 (33%) incomplete response. One-year after RAIT, children with excellent response had significantly lower stimulated thyroglobulin (sTg) compared to not excellent group (median sTg 4.4 ng/ml vs 52.5 ng/ml, p < 0.001). ROC curve showed sTg higher than 27.2 ng/ml as the most accurate to predict 1-year treatment response. After a median follow-up of 133 months, NED was present in 241 cases (87%) while persistent disease in 35 (13%). At multivariate analysis, sTg and 1-year treatment response categories were both significantly associated with the last disease status (p value 0.023 and < 0.001). CONCLUSIONS: In pediatric DTC, sTg is significantly associated with 1-year treatment response and final outcome. However, 1-year response is the principal prognostic factor able to predict pediatric DTCs outcome.

PET-Derived Radiomics and Artificial Intelligence in Breast Cancer: A Systematic Review.

Breast cancer (BC) is a heterogeneous malignancy that still represents the second cause of cancer-related death among women worldwide. Due to the heterogeneity of BC, the correct identification of valuable biomarkers able to predict tumor biology and the best treatment approaches are still far from clear. Although molecular imaging with positron emission tomography/computed tomography (PET/CT) has improved the characterization of BC, these methods are not free from drawbacks. In recent years, radiomics and artificial intelligence (AI) have been playing an important role in the detection of several features normally unseen by the human eye in medical images. The present review provides a summary of the current status of radiomics and AI in different clinical settings of BC. A systematic search of PubMed, Web of Science and Scopus was conducted, including all articles published in English that explored radiomics and AI analyses of PET/CT images in BC. Several studies have demonstrated the potential role of such new features for the staging and prognosis as well as the assessment of biological characteristics. Radiomics and AI features appear to be promising in different clinical settings of BC, although larger prospective trials are needed to confirm and to standardize this evidence.

Rhenium Radioisotopes for Medicine, a Focus on Production and Applications.

In recent decades, the use of alpha; pure beta; or beta/gamma emitters in oncology, endocrinology, and interventional cardiology rheumatology, has proved to be an important alternative to the most common therapeutic regimens. Among radionuclides used for therapy in nuclear medicine, two rhenium radioisotopes are of particular relevance: rhenium-186 and rhenium-188. The first is routinely produced in nuclear reactors by direct neutron activation of rhenium-186 via 185Re(n,γ)186Re nuclear reaction. Rhenium-188 is produced by the decay of the parent tungsten-188. Separation of rhenium-188 is mainly performed using a chromatographic 188W/188Re generator in which tungsten-188 is adsorbed on the alumina column, similar to the 99Mo/99mTc generator system, and the radionuclide eluted in saline solution. The application of rhenium-186 and rhenium-188 depends on their specific activity. Rhenium-186 is produced in low specific activity and is mainly used for labeling particles or diphosphonates for bone pain palliation. Whereas, rhenium-188 of high specific activity can be used for labeling peptides or bioactive molecules. One of the advantages of rhenium is its chemical similarity with technetium. So, diagnostic technetium analogs labeled with radiorhenium can be developed for therapeutic applications. Clinical trials promoting the use of 186/188Re-radiopharmaceuticals is, in particular, are discussed.

177Lu-PRRT in advanced gastrointestinal neuroendocrine tumors: 10-year follow-up of the IRST phase II prospective study.

PURPOSE: In March 2014, we reported the activity and safety of 177Lu-DOTA-octreotate peptide receptor radionuclide therapy (Lu-PRRT) at two different dosages (18.5 GBq and 27.5 GBq in 5 cycles) in patients with progressive metastatic gastrointestinal neuroendocrine tumors (GI-NETs). Disease control rate (DCR) and toxicity were addressed. Herein, we report the late toxicity, progression-free survival (PFS), and overall survival (OS) in the same cohort after a 10-year follow-up. METHODS: We conducted an open-label, disease-oriented prospective phase II trial. From March 2008 to June 2011, 43 patients received 3.7 GBq or 5.5 GBq of Lu-PRRT every 6 to 8 weeks, each cycle repeated 5 times. All patients showed 68Gallium-DOTA-peptide PET/Octreoscan® positivity (score 3-4 Rotterdam scale) in known lesions. Tumor burden was estimated radiologically. Time-to-event data (PFS and OS) were described using Kaplan-Meier curves and compared with the log-rank test. RESULTS: Forty-three patients (28 males and 15 females) were evaluable and were monitored for a median period of 118 months (range 12.6-139.6). Median PFS in patients receiving 18.5 GBq was 59.8 months (95% confidence interval [95% CI] 14.3-79.6), identical to that of patients treated with 27.5 GBq (59.8 months, 95% CI 23.4-82.0). Median OS was 71.0 months (95% CI 46.1-107.3) in the group who received 18.5 GBq and 97.6 months (95% CI 64.3-not reached) in the group treated with 27.5 GBq (P = 0.22). Patients with progression limited to lymph nodes showed significantly longer median PFS and OS than those with hepatic lesions (P = 0.02 for PFS and P = 0.04 for OS). Age over 65 years at the time of PRRT was also significant for OS. Of note, no late hematological or renal toxicity was observed in either group. CONCLUSIONS: The long-term follow-up of the IRST phase II study shows that Lu-PRRT is a safe and effective therapy for patients with advanced GI-NET, the most important prognostic factor being tumor burden, hepatic lesions, and age. We believe that Lu-PRRT should be offered to patients with early-stage disease.

Uncommon solitary nasal extramedullary plasmacytoma detected by 18F-FDG PET/CT.

Extramedullary plasmacytoma (EMP) is an uncommon neoplastic proliferation of monoclonal plasma cells. Despite having a better prognosis and lower conversion rate to multiple myeloma in comparison to solitary bone plasmacytoma, EMP diagnosis can be challenging. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) certainly has an established role in EMP diagnostic workup. Herein, we describe a rare case of nasal cavity EMP, highlighting 18F-FDG PET/CT potential in the detection of EMP occurring in atypical sites and providing a useful comparison in the differential diagnosis with other 18F-FDG avid nasal pathologies.

99mTc-labeled FAPI compounds for cancer and inflammation: from radiochemistry to the first clinical applications.

BACKGROUND: In recent years, fibroblast activating protein (FAP), a biomarker overexpressed by cancer-associated fibroblasts, has emerged as one of the most promising biomarkers in oncology. Similarly, FAP overexpression has been detected in various fibroblast-mediated inflammatory conditions such as liver cirrhosis and idiopathic pulmonary fibrosis. Along this trajectory, FAP-targeted positron emission tomography (PET), utilizing FAP inhibitors (FAPi) labeled with positron emitters, has gained traction as a powerful imaging approach in both cancer and inflammation. However, PET represents a high-cost technology, and its widespread adoption is still limited compared to the availability of gamma cameras. To address this issue, several efforts have been made to explore the potential of [99mTc]Tc-FAPi tracers as molecular probes for imaging with gamma cameras and single photon emission computed tomography (SPECT). MAIN BODY: Several approaches have been investigated for labeling FAPi-based compounds with 99mTc. Specifically, the mono-oxo, tricarbonyl, isonitrile, and HYNIC strategies have been applied to produce [99mTc]Tc-FAPi tracers, which have been tested in vitro and in animal models. Overall, these labeling approaches have demonstrated high efficiency and strong binding. The resulting [99mTc]Tc-FAPi tracers have shown high specificity for FAP-positive cells and xenografts in both in vitro and animal model studies, respectively. However, the majority of [99mTc]Tc-FAPi tracers have exhibited variable levels of lipophilicity, leading to preferential excretion through the hepatobiliary route and undesirable binding to lipoproteins. Consequently, efforts have been made to synthesize more hydrophilic FAPi-based compounds to improve pharmacokinetic properties and achieve a more favorable biodistribution, particularly in the abdominal region. SPECT imaging with [99mTc]Tc-FAPi has yielded promising results in patients with gastrointestinal tumors, demonstrating comparable or superior diagnostic performance compared to other imaging modalities. Similarly, encouraging outcomes have been observed in subjects with gliomas, lung cancer, breast cancer, and cervical cancer. Beyond oncological applications, [99mTc]Tc-FAPi-based imaging has been successfully employed in myocardial and idiopathic pulmonary fibrosis. CONCLUSIONS: This overview focuses on the various radiochemical strategies for obtaining [99mTc]Tc-FAPi tracers, highlighting the main challenges encountered and possible solutions when applying each distinct approach. Additionally, it covers the preclinical and initial clinical applications of [99mTc]Tc-FAPi in cancer and inflammation.

The Future Direction of Women in Nuclear Medicine and Nuclear Medicine in Women's Health.

This work discusses the role of Nuclear Medicine for women's health, the role of women in the development of this emerging field and the various issues which arise from both. It emphasizes the importance of young women and their competing needs due to factors like pregnancy and work-related challenges. The objectives of this overview include improving imaging techniques, preserving fertility during cancer treatment, diagnosing pelvic and uterine conditions, developing radiopharmaceuticals for women's health, protecting female employees in Nuclear Medicine, and considering the role of artificial intelligence.

The evolution of PET imaging in renal, bladder, upper urinary tract urothelial, testicular and penile carcinoma - Today's impact, tomorrow's potential.

INTRODUCTION: The advancement of hybrid PET/CT or PET/MRI imaging for non-prostate genitourinary cancers has not experienced the rapid progress of prostate cancer. Nevertheless, these neoplasms are aggressive and reliable imaging plays a pivotal role in enhancing patients' quality of life and prognosis. AREAS COVERED: the main evidence regarding [18F]FDG and non-[18F]FDG PET/CT or PET/MRI in non-prostate uro-oncological malignancies are summarized and discussed. Moreover, potential future directions concerning PET imaging in these neoplasms are debated, with the aim to stimulate future research projects covering these fields. EXPERT OPINION: In Renal Cell Carcinoma (RCC), [18F]FDG PET/CT demonstrates varying efficacy in staging, restaging, and prognostic stratification, but PSMA PET/CT is emerging as a potential game-changer, particularly in advanced, high-grade aggressive clear cell RCC. [18F]FDG PET/CT may see an increased use in N and M-staging of bladder cancer, as well as for detecting recurrence and response to neoadjuvant chemotherapy. Preliminary data regarding [68Ga]-FAPI also looks promising in this context. [18F]FDG PET/MRI could be useful for the T-staging of bladder cancer, while upper tract urothelial carcinoma still lacks of molecular imaging literature reports. In testicular and penile cancer [18F]FDG PET/CT has demonstrated its usefulness in several clinical settings, although experiences with non-[18F]FDG radiotracers are lacking.

ML Models Built Using Clinical Parameters and Radiomic Features Extracted from 18F-Choline PET/CT for the Prediction of Biochemical Recurrence after Metastasis-Directed Therapy in Patients with Oligometastatic Prostate Cancer.

Oligometastatic patients at [18F]F-Fluorocholine (18F-choline) PET/CT may be treated with metastasis-directed therapy (MDT). The aim of this study was to combine radiomic parameters extracted from 18F-choline PET/CT and clinical data to build machine learning (ML) models able to predict MDT efficacy. METHODS: Oligorecurrent patients (≤5 lesions) at 18F-choline PET/CT and treated with MDT were collected. A per-patient and per-lesion analysis was performed, using 2-year biochemical recurrence (BCR) after MDT as the standard of reference. Clinical parameters and radiomic features (RFts) extracted from 18F-choline PET/CT were used for training five ML Models for both CT and PET images. The performance metrics were calculated (i.e., Area Under the Curve-AUC; Classification Accuracy-CA). RESULTS: A total of 46 metastases were selected and segmented in 29 patients. BCR after MDT occurred in 20 (69%) patients after 2 years of follow-up. In total, 73 and 33 robust RFTs were selected from CT and PET datasets, respectively. PET ML Models showed better performances than CT Models for discriminating BCR after MDT, with Stochastic Gradient Descent (SGD) being the best model (AUC = 0.95; CA = 0.90). CONCLUSION: ML Models built using clinical parameters and CT and PET RFts extracted via 18F-choline PET/CT can accurately predict BCR after MDT in oligorecurrent PCa patients. If validated externally, ML Models could improve the selection of oligorecurrent PCa patients for treatment with MDT.

A Prospective Randomized Multicenter Study on the Impact of [18F]F-Choline PET/CT Versus Conventional Imaging for Staging Intermediate- to High-Risk Prostate Cancer.

This study aimed to compare the efficacy of [18F]F-choline PET/CT with conventional imaging for staging and managing intermediate- to high-risk prostate cancer (PCa). The primary objective was to assess the ability of PET/CT with [18F]F-choline to identify lymph node and systemic involvement during initial staging. Secondary objectives included evaluating the impact of [18F]F-choline PET/CT on unnecessary local treatments and assessing the safety of [18F]F-choline agents. Additionally, the study aimed to analyze recurrence-free survival and overall survival 5 y after randomization. Methods: A prospective controlled, open, randomized multicenter phase III trial involving 7 Italian centers was conducted. Eligible patients with intermediate- to high-risk PCa were randomized in a 1:1 ratio. Two groups were formed: one undergoing conventional imaging (abdominopelvic contrast-enhanced CT and bone scanning) and the other receiving conventional imaging plus [18F]F-choline PET/CT. The study was terminated prematurely; however, all the endpoints were thoroughly analyzed and enriched. Results: Between February 2016 and December 2020, 256 patients were randomly assigned. In total, 236 patients (117 in the control arm and 119 in the experimental arm) were considered for the final assessment. In the experimental arm, the sensitivity for lymph node metastases, determined by final pathology and serial prostate-specific antigen evaluations, was higher than in the control arm (77.78% vs. 28.57% and 65.62% vs. 17.65%, respectively). The [18F]F-choline was tolerated well. The use of [18F]F-choline PET/CT resulted in an approximately 8% reduction in unnecessary extended lymphadenectomy compared with contrast-enhanced CT. Additionally, [18F]F-choline PET/CT had a marginal impact on 5-y overall survival, contributing to a 4% increase in survival rates. Conclusion: In the initial staging of PCa, [18F]F-choline PET/CT exhibited diagnostic performance superior to that of conventional imaging for detecting metastases. [18F]F-choline PET/CT reduced the rate of unnecessary extensive lymphadenectomy by up to 8%. These findings support the consideration of discontinuing conventional imaging for staging PCa.

Diverse Imaging Methods May Influence Long-Term Oncologic Outcomes in Oligorecurrent Prostate Cancer Patients Treated with Metastasis-Directed Therapy (the PRECISE-MDT Study).

Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. Methods: We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. Results: Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by [18F]fluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio [HR], 0.49 [95% CI, 0.36-0.67]; P < 0.0001), PFS2 (HR, 0.42 [95% CI, 0.28-0.63]; P < 0.0001), and overall survival (HR, 0.39 [95% CI, 0.15-0.99]; P < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent [68Ga]Ga-PSMA-11 versus [18F]F-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 [95% CI, 0.26-1.00]; P < 0.05; PFS2: HR, 0.24 [95% CI, 0.09-0.60]; P < 0.05). Conclusion: Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings.

[18F]-FDHT PET for the Imaging of Androgen Receptor in Prostate and Breast Cancer: A Systematic Review.

The aim of this systematic review is to provide a comprehensive overview of the role of fluoro-5α-dihydrotestosterone ([18F]-FDHT) for the in vivo imaging of androgen receptors (AR) through positron emission tomography (PET) in metastatic breast (mBC) and metastatic castration-resistant prostate cancer (mCRPC). Relevant studies published from 2013 up to May 2023 were selected by searching Scopus, PubMed and Web of Science. The selected imaging studies were analyzed using a modified version of the critical Appraisal Skills Programme (CASP). Eleven studies encompassing 321 patients were selected. Seven of the eleven selected papers included 266 subjects (82.2%) affected by mCRPC, while four encompassed 55 (17.2%) patients affected by mBC. [18F]-FDHT PET showed a satisfying test/retest reproducibility, and when compared to a histochemical analysis, it provided encouraging results for in vivo AR quantification both in mCRPC and mBC. [18F]-FDHT PET had a prognostic relevance in mCRPC patients submitted to AR-targeted therapy, while a clear association between [18F]-FDHT uptake and the bicalutamide response was not observed in women affected by AR-positive mBC. Further studies are needed to better define the role of [18F]-FDHT PET, alone or in combination with other tracers (i.e., [18F]-FDG/[18F]-FES), for patients' selection and monitoring during AR-targeted therapy, especially in the case of mBC.

Hepato-Biliary Imaging in an Acute Setting: Is There a Role for Nuclear Medicine?

Nuclear medicine (NM) is not commonly considered as a first-line imaging modality in hepato-biliary (HB) emergencies. The aim of this review is to provide an update on the potential of NM for the imaging of HB emergencies. 99mTc-HIDA scintigraphy showed high diagnostic accuracy for acute cholecystitis, thus being particularly useful in patients at high-risk for surgery due to comorbidities and with no clear findings at US or CT. Although limitedly explored, White blood cell (WBC) scan might have a role in case of acute pancreatitis, especially for the imaging of pancreatic leukocyte infiltration and the prediction of pancreatic necrosis. Scientific literature on 18F-FDG-PET/CT in HB acute disease mainly consists of case reports or case series, describing incidental findings in oncological PET/CT scans. In patients with obstructive jaundice, PET/CT has been proposed to disclose and characterize occult tumoral etiology. Further studies are needed to evaluate the clinical usefulness of the various NM approaches in HB acute settings, particularly with respect to the emerging new technologies (eg, PET/MRI) and radiopharmaceuticals.

18 F-Choline Versus 68 Ga-PSMA-11 PET/CT Imaging Comparison in Incidental Clear Cell Renal Cell Carcinoma.

ABSTRACT: Few articles in literature describe the potential usefulness of 18 F-choline PET/CT and particularly 68 Ga-PSMA-11 PET/CT in imaging of clear cell renal cell carcinoma (ccRCC). We report a unique comparison in literature between the 2 radiotracers in a patient who underwent left nephrectomy with diagnosis of ccRCC, grade 3. 68 Ga-PSMA-11 PET/CT confirmed its emerging role in imaging ccRCC, as the incidentally detected renal neoplasm showed a significant higher uptake in comparison to 18 F-choline PET/CT, inducing surgical indication.

Superscan-Like Pattern on 18F-Choline PET/CT in a Patient With Essential Thrombocythemia.

ABSTRACT: Few clinical and preclinical articles reported the potential usefulness of 18F-choline PET/CT in several hematological proliferative diseases. We report and incidental finding of a superscan-like pattern in a patient affected by essential thrombocythemia (ET), performing 18F-choline PET/CT for a biochemical recurrence of prostate cancer. The mild elevation of PSA values and the negativity of subsequent 68Ga-PSMA-11 PET/CT allowed to correlate the diffuse skeletal uptake detected on 18F-choline PET/CT to the underlying hematologic disease, rather than to a prostate cancer relapse.

FDG PET/CT Volume-Based Quantitative Data and Survival Analysis in Breast Cancer Patients: A Systematic Review of the Literature.

PURPOSE: The study aims to assess the role of SUVs, MTV, TLG, and other FDG PET metric data in predicting the prognosis of patients with newly diagnosed BC. MATERIALS AND METHODS: A systematic review was conducted by using three different databases: Pub- Med, Web of Science, and EMBASE, in the period between January 2011 and May 2021. Studies on the use of FDG PET in BC patients concerning the utility of metric PET data and survival were retrieved. The following keywords were used in diverse combinations: "breast cancer", "18F-FDG", "FDG", "PET", "PET/CT", "FDG PET", "volumetric parameters", "metabolic tumor volume", "MTV", "total lesion glycolysis", "TLG", "prognosis", "prognostic". No limits were applied. The quality of selected papers was assessed by using specific criteria. RESULTS: Totally 123 articles were retrieved, but only 14 studies were selected. In the selected papers, overall, the number of patients was 1850. Overall survival (OS) was the main outcome in three studies, while both OS and disease-free survival (DFS) were considered in the remainder of most papers. PET/CT was performed in patients with BC before surgery or neoadjuvant chemotherapy in 6 studies and in metastatic BC in 8. At multivariable analyses, diverse PET metrics, such as SUVmax, MTV, and TLG, were correlated to recurrence or OS. However, a large heterogeneity for the proposal cut-off, able to discriminate between poor and good prognosis, was found. CONCLUSION: PET metrics are helpful for the prognosis stratification in patients with locally advanced or metastatic BC. However, no specific cut-off values for these variables are now available in this setting of patients.

Misinterpretation of an inflammatory FDG uptake in a patient treated for Hodgkin lymphoma: a case report.

Hodgkin Lymphoma (HL) is a malignancy involving lymph nodes and lymphatic system. [18F]F-FDG PET/CT (FDG-PET) imaging is routinely used for staging, to assess early chemotherapy response (interim FDG-PET), at the end of treatment (EoT FDG-PET) and for the identification of disease recurrence. We present a case of a 39-year-old man treated for HL. FDG-PET scans performed after first line therapy (both Interim PET and at the end of therapy) demonstrated a persistent and significant mediastinal FDG uptake. The patient was treated with a second line therapy but the FDG-PET uptake did not change. After board discussion a new surgical, thoracoscopy-guided biopsy was performed. Histopathology demonstrated a dense fibrous tissue with occasional chronic inflammatory infiltrates. Persistent FDG-PET positivity may suggest refractory or relapsed disease. However, occasionally, non-malignant conditions are responsible for a persistent FDG uptake, not related to primary disease. An accurate evaluation of clinical history and previous imaging exams is mandatory for clinicians and others experts to avoid misinterpretations of FDG-PET results. Nevertheless, in some cases, only a more invasive procedure, such as a biopsy, may finally lead to a definitive diagnosis.

18F-FDG PET-Derived Volume-Based Parameters to Predict Disease-Free Survival in Patients with Grade III Breast Cancer of Different Molecular Subtypes Candidates to Neoadjuvant Chemotherapy.

We investigated whether baseline [18F] Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each 18F-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%; p = 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%; p = 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%; p < 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline 18F-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC.

Radiomics and theranostics with molecular and metabolic probes in prostate cancer: toward a personalized approach.

INTRODUCTION: In the last decade, two new radionuclide-based therapies, 223Radichloride and radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA), have been approved by the regulatory authorities for the management of castrate-resistant prostate cancer (PCa). AREAS COVERED: The basic principles of PCa molecular imaging are illustrated, with a particular attention to the combined use of diagnosis and therapy in a unique approach (the so-called theranostics) for response prediction and assessment in patients submitted to 223Radichloride or PSMA targeted therapies. In this perspective, the potential of radiomics, an emerging discipline based on the extraction of quantitative features from medical images, is covered. EXPERT OPINION: Theranostic metabolic and molecular probes have been successfully applied to predict and monitor response to radionuclide-based therapies. In particular, both 99mTc-MDP and 18F-NaF resulted useful tools for personalized dosimetry and prognostic stratification before 223Ra-therapy, while PSMA-ligands, alone or in combination with 18F-FDG, provided valuable information to select patients who are more likely to benefit from RLT and getting information on PCa grade of differentiation and aggressiveness. In spite of its high potential, PET-radiomics for PCa is still at an embryonic phase and needs further validation.