The impact of PET imaging on triple negative breast cancer: an updated evidence-based perspective.

INTRODUCTION: Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors. It predominantly affects younger women and is associated with a poor prognosis. This systematic review aims to evaluate the current role of positron emission tomography (PET) in the management of TNBC patients and to identify future research directions. METHODS: We systematically searched the PubMed, Scopus, and Web of Science databases up to February 2024. A team of five researchers conducted data extraction and analysis. The quality of the selected studies was assessed using a specific evaluation form. RESULTS: Twenty-eight studies involving 2870 TNBC patients were included in the review. Key clinical applications of PET in TNBC included predicting pathological complete response (pCR) in patients undergoing neoadjuvant chemotherapy (NAC), assessing the prognostic value of baseline PET, and initial disease staging. Two studies utilized PSMA-ligand agents, while the majority used [18F]FDG-based PET. Significant associations were found between baseline [18F]FDG uptake and molecular biomarkers such as PDL-1, androgen receptor, and Ki67. Baseline [18F]FDG PET led to the upstaging of patients from stage IIB to stage IV, influencing treatment decisions and survival outcomes. In the NAC setting, serial PET scans measuring changes in [18F]FDG uptake, indicated by maximum standardized uptake value (SUVmax), predicted pCR with varying cut-off values correlated with different response rates. Semiquantitative parameters such as metabolic tumor volume (MTV) and PET lung index were prognostic for metastatic disease. CONCLUSIONS: In TNBC patients, [18F]FDG PET is essential for initial disease staging in both localized and metastatic settings. It is also useful for assessing treatment response to NAC. The ability of PET to correlate metabolic activity with molecular markers and predict treatment outcomes highlights its potential in TNBC management. Further prospective studies are needed to refine these clinical indications and establish its definitive role.

The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.

PURPOSE: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. METHODS: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. RESULTS: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). CONCLUSION: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

Update on Rheumatic Diseases in Clinical Practice: Recent Concepts and Developments.

Diagnostic imaging is essential in the diagnostic process of rheumatic diseases. Given the heterogeneity of this group of diseases and the tremendous impact of novel therapeutic options, guidelines and recommendations regarding the optimal choice of the most appropriate technique/s are continuously revised and radiologists should always be up-to-date. Last, because of the continuous technological innovations, we will assist to the progressive application of advanced techniques and tools in rheumatology.

Non-palpable Pulmonary Nodules and Uniportal-VATS: Radio-guided Localization (ROLL) Experience of a Lung Multidisciplinary Team.

BACKGROUND/AIM: Surgical resection with a minimally invasive approach is the standard for diagnosing and treating solitary pulmonary nodules. A computed tomography (CT)-guided technetium99m-macroaggregated albumin (99mTc-MAA) injection-based procedure has been employed for small and non-palpable lung nodule radio-guided preoperative localization (ROLL). This procedure is usually followed by video-assisted thoracoscopic surgery (VATS). This study retrospectively evaluated the feasibility, clinicopathologic outcomes, and complications of this localization radio-guided procedure followed by uniportal VATS. PATIENTS AND METHODS: This retrospective study included 63 patients with suspicious lung nodules who underwent 99mTc-MAA CT-guided localization before uniportal VATS. The analysis examined the imaging and procedure characteristics, procedural risks, successful intra-operative localization, wedge resection, conversion from VATS to open thoracotomy, the reason, and histological diagnosis for each nodule. Also, it was evaluated how nodule and procedure features affected successful intra-operative localization. RESULTS: All patients were diagnosed using a CT scan, and 90.4% had a PET scan at basal staging. A round-glass morphology was present in 9.6% of cases, whereas most had a solid appearance. The mean nodule size was 9.78 mm (maximal tumoral diameter) with a 1-23 mm range. The mean distance from the pleural surface was 15.6 mm (range=1-117 mm). The detection rate of the 99mTc-MAA CT-guided localization procedure was 100%. Surgical procedures were uniportal VATS and transpleural thoracoscopy in 52 (82.5%) and 11 (17.5%) patients, respectively. The intraoperative localization rate was 98.4%. Pneumothorax represented the most frequent complication (6.3%), with one case clinically significant and three only with minimal radiological evidence. Pathology confirmed radical excision in all cases. CONCLUSION: Lung nodule localization with CT-guided 99mTc-MAA followed by uniportal VATS is feasible with a high success rate and low complication rate.

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.

Prostate cancer: nuclear medicine imaging in the biochemical recurrence and in oligometastatic disease.

INTRODUCTION: The aim of this article was to offer a comprehensive non-systematic review of the literature about the use of Nuclear Medicine imaging exams for the evaluation of prostate cancer (PCa) in the recurrent setting, with a particular regard to positron emission tomography/computed tomography (PET/CT) imaging. EVIDENCE ACQUISITION: A comprehensive nonsystematic literature review was performed in March 2024. Literature search was updated until March 2024. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations. EVIDENCE SYNTHESIS: Restaging BCR with advanced Nuclear Medicine Imaging, such as prostate-specific membrane antigen-PET/CT could lead to stage migration and pave the way for additional management strategies, such as stereotactic ablative radiotherapy in patients with low-burden or oligometastatic disease, potentially delaying the need of systemic therapies. While OS benefits of targeting PET/CT positive disease are still lacking, data on progression- and metastasis-free-survival are emerging. Improvements in quality-of-life assessments are already evident. CONCLUSIONS: PCa is one of the most common malignancy in men. In the last 10 years PCa imaging has become significantly more accurate and is now essential for the definition of the extent of the disease in different phases of its natural history. This opened the road to novel management strategies, especially in the recurrent setting, in which the oligometastatic state is now being explored in several trials regarding the prognostic significance of metastasis directed therapies aimed at personalizing the treatment for every single patient.

New target therapies in prostate cancer: from radioligand therapy, to PARP-inhibitors and immunotherapy.

Prostate cancer (PCa) remains a significant global health challenge, particularly in its advanced stages. Despite progress in early detection and treatment, PCa is the second most common cancer diagnosis among men. This review aims to provide an overview of current therapeutic approaches and innovations in PCa management, focusing on the latest advancements and ongoing challenges. We conducted a narrative review of clinical trials and research studies, focusing on PARP inhibitors (PARPis), phosphoinositide 3 kinase-protein kinase B inhibitors, immunotherapy, and radioligand therapies (RLTs). Data was sourced from major clinical trial databases and peer-reviewed journals. Androgen deprivation therapy and androgen-receptor pathway inhibitors remain foundational in managing castration-sensitive and early-stage castration-resistant PCa (CRPC). PARPi's, such as olaparib and rucaparib, have emerged as vital treatments for metastatic CRPC with homologous recombination repair gene mutations, highlighting the importance of personalized medicine. Immune checkpoint inhibitors (ICIs) have shown clinical benefit limited to specific subgroups of PCa, demonstrating significant improvement in efficacy in patients with microsatellite instability/mismatch repair or cyclin-dependent kinase 12 alteration, highlighting the importance of focusing ongoing research on identifying and characterizing these subgroups to maximize the clinical benefits of ICIs. RLTs have shown effectiveness in treating mCRPC. Different alpha emitters (like [225Ac]PSMA) and beta emitters compounds (like [177Lu]PSMA) impact treatment differently due to their energy transfer characteristics. Clinical trials like VISION and TheraP have demonstrated positive outcomes with RLT, particularly [177Lu]PSMA-617, leading to FDA approval. Ongoing trials and future perspectives explore the potential of [225Ac]PSMA, aiming to improve outcomes for patients with mCRPC. The landscape of PCa treatment is evolving, with significant advancements in both established and novel therapies. The combination of hormonal therapies, chemotherapy, PARPis, immunotherapy, and RLTs, guided by genetic and molecular insights, opens new possibilities for personalized treatment.

Advancements in Neuroendocrine Neoplasms: Imaging and Future Frontiers.

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management.

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.

18 F-FET PET/CT in Calcifying Pseudoneoplasm of the Neuraxis : First Case.

ABSTRACT: A 66-year-old man has been treated in a psychiatric department for 4-5 years for a depressive syndrome, which is associated with poor motor initiative, confusional state, and dysosmia. Dynamic 18 F-FET PET/CT showed only faint uptake of radiotracer just above the background on the left frontal calcific lesion. The time-activity curve of the neoplasms showed a descending pattern. After a left fronto-orbitary minicraniotomy surgery, histology examination concluded for a rare calcifying pseudoneoplasm of the neuraxis (CAPNON). To our knowledge, no data are available on the metabolic behavior of CAPNON in 18 F-FET PET/CT. This case highlighted that a faint uptake and descending pattern on dynamic 18 F-FET PET/CT may be helpful in suspected CAPNON before surgery.

FAPi-Based Agents in Thyroid Cancer: A New Step towards Diagnosis and Therapy? A Systematic Review of the Literature.

(1) Background: Thyroid cancer (TC) is often treated with surgery followed by iodine-131. Up to 50% of the instances of TC lose their avidity to 131I, becoming more aggressive. In this scenario, [18F]FDG PET/CT imaging is used for evaluating the widespread nature of the disease, despite its low sensitivity and a false negative rate of 8-21.1%. A novel class of PET agents targeting the fibroblast activation protein inhibitor (FAPi) has emerged, studied particularly for their potential application to theranostics. (2) Methods: A search of the literature was performed by two independent authors (P.G. and L.E.) using the PubMed, Scopus, Web of Science, Cochrane Library, and EMBASE databases. The following terms were used: "FAP" or "FAPi" or "Fibroblast activating protein" and "thyroid" or "thyroid cancer", in different combinations. The included papers were original articles, clinical studies, and case reports in the English language. No time limits were used. Editorials, conference papers, reviews, and preclinical studies were excluded. (3) Results: There were 31 papers that were selected. Some studies reported a low or absent FAPi uptake in TC lesions; others reported promising findings for the detection of metastases. (4) Conclusions: The preliminary results are encouraging. FAPI agents are an alternative to [18F]FDG and a promising theranostic tool. However, further studies with a larger population are needed.

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.

Multicentric study on 18F-FDG-PET/CT breast incidental uptake in patients studied for non-breast malignant purposes / Estudio multicéntrico sobre la captación incidental en la mama con 18F-FDG-PET/TAC en pacientes evaluados con fines oncológicos no relacionados con la patología mamaria

Aim. Our study has aimed to establish the prevalence and pathological nature of fluorine-18-fluorodeoxyglucose (18F-FDG) breast incidental uptake (BIU) in patients studied for non-malignant breast tumours and then to compare our data obtained in three Italian nuclear medicine centres with those available in literature. Material and methods. We retrospectively evaluated 42,927 18F-FDG-PET/CT scans performed on patients studied in three Italian Nuclear Medicine Centres. All patients underwent 18F-FDG-PET/CT for oncologic purposes not related to breast disease. Results. Among 42,927 scans, a BIU was identified in 79 (0.18%) patients, 75 (95%) female and 4 (5%) male with an average age of 62 ± 17 years. Twenty-five out of 35 (71.5%) BIUs were malignant and 10/35 (28.5%) benign. Among the 25/35 incidentalomas that were malignant, 12/25 (48%) were infiltrating ductal carcinoma, 5/25 (20%) ductal carcinoma (infiltrating and in situ), 4/25 (16%) lobular carcinoma, 2/25 (8%) ductal carcinoma in situ and 2/25 (8%) were metastases from the primary tumour under investigation. Of the 10 BIUs that were benign in the histological examination, after further investigations it was found that 9/10 (90%) were fibroadenomas and 1/10 (10%) was a benign lesion not better specified. The lesion to liver or to blood-pool SUVmax ratio in malignant lesions is significantly higher than in benign ones. Conclusions. Our multicenter study demonstrates that, although they are uncommon, BIUs show a high percentage of malignancy and therefore requires further research (AU)

Objetivo. Objetivo de nuestro estudio fue establecer la prevalencia y el carácter patológico de la captación incidental en la mama (CIM) de 18F-FDG en pacientes evaluados para tumores malignos de origen no-mamario y luego comparar nuestros datos obtenido en tres centros Italianos de Medicina Nuclear con los que están disponibles en literatura. Material y métodos. Hemos evaluado retrospectivamente 42.927 estudios 18F-FDG-PET/TAC de pacientes en tres centros Italianos de Medicina Nuclear; todos los pacientes se han sometidos a una exploración 18F-FDG-PET/TAC por fines oncológicos no relacionados con la patología mamaria. Resultados. Entre 42.927 exploraciones, una CIM fue identificada en 79 (0.18%) pacientes, 75 (95%) mujeres y 4 (5%) hombres, con una edad media de 62 ± 17 años. Veinticinco de 35 (71.5%) CIM fueron malignas y 10/35 (28.5%) benignas. Entre los incidentalomas malignos, 12/25 (48%) eran carcinomas ductales infiltrantes, 5/25 (20%) carcinomas ductales (infiltrantes e in situ), 4/25 (16%) carcinomas lobulares, 2/25 (8%) carcinomas ductales in situ y 2/25 (8%) eran metástasis de tumour primario objeto de investigación. Entre 10 CIM que fueron identificados como benignos en el examen histológico después de investigación adicional, 9/10 (90%) fueron fibroadenomas y 1/10 (10%) fue una lesión benigna no mejor especificada. El ratio del SUVmáx de la lesión en comparación con el hígado o con el pool vascular es significativamente mayor en las lesiones malignas que en las benignas. Conclusiones. Nuestro estudio multicéntrico demuestra que, aunque son poco frecuentes, las CIM muestran un alto porcentaje de malignidad, por lo tanto las CIM necesitan investigación adicional (AU)