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.

Summary: SNMMI Procedure Standard/EANM Practice Guideline for Estrogen Receptor Imaging of Patients with Breast Cancer Using 16α-[18F]Fluoro-17ß-Estradiol PET.

The estrogen receptor (ER), a steroid hormone receptor important in female physiology, is a significant contributor to breast carcinogenesis and progression and, as such, is an important therapeutic target. Approximately 70% of breast cancers will express ER at presentation, and the determination of ER expression by tissue assay, usually by immunohistochemistry, is part of the standard of care for newly diagnosed breast cancer. ER expression is important in guiding the approach to treatment, especially with the increase in relevant systemic therapies. The ER-targeting imaging agent 16α-[18F]fluoro-17ß-estradiol ([18F]FES) is approved for clinical use by regulatory agencies in France and the United States. Multiple studies suggest the advantages of [18F]FES PET in assessing tumor ER expression, the ability of both qualitative and quantitative [18F]FES PET measures to predict response to ER-targeted therapy, and the ability of [18F]FES PET to clarify equivocal staging and restaging results in patients with ER-expressing cancers. [18F]FES PET/CT may also be helpful in staging invasive lobular breast cancer and low-grade ER-expressing invasive ductal cancers and, in some cases, may be a substitute for biopsy. The Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine in June 2023 released a procedure standard/practice guideline for [18F]FES PET ER imaging of patients with breast cancer. The goal of the standard/guideline is to assist physicians in recommending, performing, interpreting, and reporting the results of [18F]FES PET studies for patients with breast cancer and to provide clinicians with the best available evidence, inform them about areas where robust evidence is lacking, and help them deliver the best possible diagnostic efficacy and study quality for their patients. Also reviewed are standardized quality control, quality assurance, and imaging procedures for [18F]FES PET. The authors emphasize the importance of precision, accuracy, repeatability, and reproducibility for both clinical management of patients and for use of [18F]FES PET in multicenter trials. A standardized imaging procedure, in combination with already published appropriate-use criteria, will help promote the use of [18F]FES PET and enhance subsequent research. This brief summary article reviews the content of the joint standard/guideline, which is available in its entirety at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=6414&navItemNumbe=10790.

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.

PSMA PET/CT in Castration-Resistant Prostate Cancer: Myth or Reality?

BACKGROUND: prostate-specific membrane antigen (PSMA) ligand PET has been recently incorporated into international guidelines for several different indications in prostate cancer (PCa) patients. However, there are still some open questions regarding the role of PSMA ligand PET in castration-resistant prostate cancer (CRPC). The aim of this work is to assess the clinical value of PSMA ligand PET/CT in patients with CRPC. RESULTS: PSMA ligand PET has demonstrated higher detection rates in comparison to conventional imaging and allows for a significant reduction in the number of M0 CRPC patients. However, its real impact on patients' prognosis is still an open question. Moreover, in CRPC patients, PSMA ligand PET presents some sensitivity and specificity limitations. Due to its heterogeneity, CRPC may present a mosaic of neoplastic clones, some of which could be PSMA-/FDG+, or vice versa. Likewise, unspecific bone uptake (UBU) and second primary neoplasms (SNPs) overexpressing PSMA in the neoangiogenic vessels represent potential specificity issues. Integrated multi-tracer imaging (PSMA ligand and [18F]FDG PET) together with a multidisciplinary discussion could allow for reaching the most accurate evaluation of each patient from a precision medicine point of view.

Molecular imaging of PARP in cancer: state-of-the-art.

INTRODUCTION: Poly-ADP-ribose-polymerase inhibitors (PARPi), which exploit the processes of so-called 'synthetic lethality,' have been successfully implemented in oncological practice. However, not all patients respond to PARPi, and there is an unmet need for noninvasive biomarkers suitable for patient selection and monitoring during PARPi therapy. AREAS COVERED: The first clinical applications of molecular imaging with positron emission tomography/computed tomography (PET/CT) with [18F]-FluorThanatrace ([18F]-FTT) and [18F]-PARPi, highly effective PARP-ligands, in patients with several malignancies (head and neck, ovarian, prostate, and breast cancer) are covered, with a particular focus on its potential for pre-treatment selection and follow-up. EXPERT OPINION: By a search made on the most common database, such as PubMed and Google Scholar in a period from January 2010 and 2023, first clinical evidence suggests that PET/CT with [18F]-FTT and [18F]-PARPi might represent a reliable tool for in vivo imaging and quantification of PARP-1 expression in ovarian, prostate, breast, head, and neck cancer, supporting their potential usefulness for patient selection before PARPi-therapies. In addition, a reduction in [18F]-FTT uptake has been registered after therapy initiation and seems to be correlated with patient outcome after PARPi-based regimens. Further studies are needed to better address the value of PARPI-radiolabeled PET imaging in these clinical settings, especially as it concerns technical features such as optimal scan modality (dynamic vs. static) and timing.

Incidental Detection of Sarcomatoid Lung Cancer by [18F] Choline Positron Emission Tomography/Computed Tomography.

A 79-year-old man treated for prostate cancer (PCa) in 2018 with concurrent hormone therapy and radical radiotherapy (RT) was given metastasis-directed RT because of skeletal progression of PCa in 2021. On [18F]-choline positron emission tomography/computed tomography (CT) for biochemical recurrence (prostate-specific antigen level: 4.96 ng/mL), he showed significant uptake in multiple skeletal lesions and focal uptake in a left lung nodule. CT-guided biopsy revealed a sarcomatoid lung carcinoma. This case confirms that histopathological evaluation is mandatory in the event of significant radiolabeled choline uptake in a single lung nodule.

Head-to-Head Comparison of FDG and Radiolabeled FAPI PET: A Systematic Review of the Literature.

FAPI-based radiopharmaceuticals are a novel class of tracers, mainly used for PET imaging, which have demonstrated several advantages over [18F]FDG, especially in the case of low-grade or well-differentiated tumors. We conducted this systematic review to evaluate all the studies where a head-to-head comparison had been performed to explore the potential utility of FAPI tracers in clinical practice. FAPI-based radiopharmaceuticals have shown promising results globally, in particular in detecting peritoneal carcinomatosis, but studies with wider populations are needed to better understand all the advantages of these new radiopharmaceuticals.

Radio-Guided Lung Surgery: A Feasible Approach for a Cancer Precision Medicine.

BACKGROUND: Radio-guided surgery is a reliable approach used for localizing ground-glass opacities, lung nodules, and metastatic lymph nodes. Lung nodules, lymph node metastatic involvement, and ground-glass opacities often represent a challenge for surgical management and clinical work-up. METHODS: PubMed research was conducted from January 1997 to June 2023 using the keywords "radioguided surgery and lung cancer". RESULTS: Different studies were conducted with different tracers: technetium-99m-albumin macroaggregates, cyanoacrylate combined to technetium-99m-sulfur colloid, indium-111-pentetreotide, and fluorine-18-deoxyglucose. A study proposed naphthalocyanine radio-labeled with copper-64. Radio-guided surgery has been demonstrated to be a reliable approach in localizing a lesion, and has a low radiological burden for personnel exposure and low morbidity. The lack of necessity to conduct radio-guided surgery under fluoroscopy or echography makes this radio-guided surgery an easy way of performing precise surgical procedures. CONCLUSIONS: Radio-guided surgery is a feasible approach useful for the intraoperative localization of ground-glass opacities, lung nodules, and metastatic lymph nodes. It is a valid alternative to the existing approaches due to its low cost, associated low morbidity, the possibility to perform the procedure after several hours, the low radiation dose applied, and the small amount of time that is required to perform it.

Prostate MRI and PSMA-PET in the Primary Diagnosis of Prostate Cancer.

Over the last years, prostate magnetic resonance imaging (MRI) has gained a key role in the primary diagnosis of clinically significant prostate cancer (csPCa). While a negative MRI can avoid unnecessary prostate biopsies and the overdiagnosis of indolent cancers, a positive examination triggers biopsy samples targeted to suspicious imaging findings, thus increasing the diagnosis of csPCa with a sensitivity and negative predictive value of around 90%. The limitations of MRI, including suboptimal positive predictive values, are fueling debate on how to stratify biopsy decisions and management based on patient risk and how to correctly estimate it with clinical and/or imaging findings. In this setting, "next-generation imaging" imaging based on radiolabeled Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is expanding its indications both in the setting of primary staging (intermediate-to-high risk patients) and primary diagnosis (e.g., increasing the sensitivity of MRI or acting as a problem-solving tool for indeterminate MRI cases). This review summarizes the current main evidence on the role of prostate MRI and PSMA-PET as tools for the primary diagnosis of csPCa, and the different possible interaction pathways in this setting.

PET/CT in Prostate Cancer.

Over the last decade, PET/CT has played a crucial role in managing patients with prostate cancer (PCa), significantly impacting various aspects of the disease [...].

[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.