Standardized template for clinical reporting of PSMA PET/CT scans.

PURPOSE: Accurate diagnosis and staging of prostate cancer are crucial to improving patient care. Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography with computed tomography (PET/CT) imaging has demonstrated superiority for initial staging and restaging in patients with prostate cancer. Referring physicians and PET/CT readers must agree on a consistent communication method and application of information derived from this imaging modality. While several guidelines have been published, a single PSMA PET/CT reporting template has yet to be widely adopted. Based on the consensus from community and academic physicians, we developed a standardized PSMA PET/CT reporting template for radiologists and nuclear medicine physicians to report and relay key imaging findings to referring physicians. The aim was to improve the quality, clarity, and utility of imaging results reporting to facilitate patient management decisions. METHODS: Based on community and expert consensus, we developed a standardized PSMA PET/CT reporting template to deliver key imaging findings to referring clinicians. RESULTS: Core category components proposed include a summary of any prior treatment history; presence, location, and degree of PSMA radiopharmaceutical uptake in primary and/or metastatic tumor(s), lesions with no uptake, and incidentally found lesions with positive uptake on PET/CT. CONCLUSIONS: This article provides recommendations on best practices for standardized reporting of PSMA PET/CT imaging. The generated reporting template is a proposed supplement designed to educate and improve data communication between imaging experts and referring physicians.

Multiparametric Whole-Body MRI: A Game Changer in Metastatic Prostate Cancer.

Prostate cancer ranks among the most prevalent tumours globally. While early detection reduces the likelihood of metastasis, managing advanced cases poses challenges in diagnosis and treatment. Current international guidelines support the concurrent use of 99Tc-Bone Scintigraphy and Contrast-Enhanced Chest and Abdomen CT for the staging of metastatic disease and response assessment. However, emerging evidence underscores the superiority of next-generation imaging techniques including PSMA-PET/CT and whole-body MRI (WB-MRI). This review explores the relevant scientific literature on the role of WB-MRI in metastatic prostate cancer. This multiparametric imaging technique, combining the high anatomical resolution of standard MRI sequences with functional sequences such as diffusion-weighted imaging (DWI) and bone marrow relative fat fraction (rFF%) has proved effective in comprehensive patient assessment, evaluating local disease, most of the nodal involvement, bone metastases and their complications, and detecting the increasing visceral metastases in prostate cancer. It does have the advantage of avoiding the injection of contrast medium/radionuclide administration, spares the patient the exposure to ionizing radiation, and lacks the confounder of FLARE described with nuclear medicine techniques. Up-to-date literature regarding the diagnostic capabilities of WB-MRI, though still limited compared to PSMA-PET/CT, strongly supports its widespread incorporation into standard clinical practice, alongside the latest nuclear medicine techniques.

ß1600 Q.Clear Digital Reconstruction of [68Ga]Ga-DOTANOC PET/CT Improves Image Quality in NET Patients.

Background: Image reconstruction is crucial for improving overall image quality and diagnostic accuracy. Q.Clear is a novel reconstruction algorithm that reduces image noise. The aim of the present study is to assess the preferred Q.Clear ß-level for digital [68Ga]Ga-DOTANOC PET/CT reconstruction vs. standard reconstruction (STD) for both overall scan and single-lesion visualization. Methods: Inclusion criteria: (1) patients with/suspected neuroendocrine tumors included in a prospective observational monocentric study between September 2019 and January 2022; (2) [68Ga]Ga-DOTANOC digital PET/CT and contrast-enhanced-CT (ceCT) performed at our center at the same time. Images were reconstructed with STD and with Q.Clear ß-levels 800, 1000, and 1600. Scans were blindly reviewed by three nuclear-medicine experts: the preferred ß-level reconstruction was independently chosen for the visual quality of both the overall scan and the most avid target lesion < 1 cm (t) and >1 cm (T). PET/CT results were compared to ceCT. Semiquantitative analysis was performed (STD vs. ß1600) in T and t concordant at both PET/CT and ceCT. Subgroup analysis was also performed in patients presenting discordant t. Results: Overall, 52 patients were included. ß1600 reconstruction was considered superior over the others for both overall scan quality and single-lesion detection in all cases. The only significantly different (p < 0.001) parameters between ß1600 and STD were signal-to-noise liver ratio and standard deviation of the liver background. Lesion-dependent parameters were not significantly different in concordant T (n = 37) and t (n = 10). Among 26 discordant t, when PET was positive, all findings were confirmed as malignant. Conclusions: ß1600 Q.Clear reconstruction for [68Ga]Ga-DOTANOC imaging is feasible and improves image quality for both overall and small-lesion assessment.

Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.

PURPOSE: Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT. METHODS: A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/ß=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis. CONCLUSIONS: Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.

Molecular imaging of thyroid and parathyroid diseases.

INTRODUCTION: Molecular imaging of thyroid and parathyroid diseases has changed in recent years due to the introduction of new radiopharmaceuticals and new imaging techniques. Accordingly, we provided an clinicians-oriented overview of such techniques and their indications. AREAS COVERED: A review of the literature was performed in the PubMed, Web of Science, and Scopus without time or language restrictions through the use of one or more fitting search criteria and terms as well as through screening of references in relevant selected papers. Literature up to and including December 2023 was included. Screening of titles/abstracts and removal of duplicates was performed and the full texts of the remaining potentially relevant articles were retrieved and reviewed. EXPERT OPINION: Thyroid and parathyroid scintigraphy remains integral in patients with thyrotoxicosis, thyroid nodules, differentiated thyroid cancer and, respectively, hyperparathyroidism. In the last years positron-emission tomography with different tracers emerged as a more accurate alternative in evaluating indeterminate thyroid nodules [18F-fluorodeoxyglucose (FDG)], differentiated thyroid cancer [124I-iodide, 18F-tetrafluoroborate, 18F-FDG] and hyperparathyroidism [18F-fluorocholine]. Other PET tracers are useful in evaluating relapsing/advanced forms of medullary thyroid cancer (18F-FDOPA) and selecting patients with advanced follicular and medullary thyroid cancers for theranostic treatments (68Ga/177Ga-somatostatin analogues).

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.

Immunohistochemistry analysis of PSMA expression at prostatic biopsy in high-risk prostate cancer: potential implications for PSMA-PET patient selection.

Introduction: Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole-mount specimens and PSMA-PET parameters. Methods: We included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated. Results: Forty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen's kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg <20% had a higher concordance in VS and VP (Cohen's kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (p = 0.3) and PSMA-TL (p = 0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (p = 0.04). Higher SUVmax was associated with membranous and combined VP expression (p = 0.008). No difference emerged between patients with PSMA%neg <20% or PSMA%neg >20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (p = 0.5, p = 0.5, and p = 0.9 respectively). Conclusions: We found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg <20% seems to have a better concordance in terms of visual score.

Imaging of Neuroendocrine Neoplasms; Principles of Treatment Strategies. What Referring Clinicians Want to Know.

ABSTRACT: Neuroendocrine neoplasms (NENs) are a diverse group of tumors that express neuroendocrine markers and primarily affect the lungs and digestive system. The incidence of NENs has increased over time due to advancements in imaging and diagnostic techniques. Effective management of NENs requires a multidisciplinary approach, considering factors such as tumor location, grade, stage, symptoms, and imaging findings. Treatment strategies vary depending on the specific subtype of NEN. In this review, we will focus on treatment strategies and therapies including the information relevant to clinicians in order to undertake optimal management and treatment decisions, the implications of different therapies on imaging, and how to ascertain their possible complications and treatment effects.

Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.

Radionuclide Theranostics in Neuroendocrine Neoplasms: An Update.

PURPOSE OF REVIEW: This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with positron emission tomography (PET) and treatment with peptide receptor radionuclide therapy (PRRT). RECENT FINDINGS: Following NETTER-1 trial, PRRT with [177Lu]Lu-DOTATATE was approved by FDA and EMA and is routinely employed in advanced G1 and G2 SST (somatostatin receptor)-expressing NET. Different approaches have been proposed so far to improve the PRRT therapeutic index, encompassing re-treatment protocols, combinations with other therapies and novel indications. Molecular imaging holds a potential added value in characterizing disease biology and heterogeneity using different radiopharmaceuticals (e.g., SST and FDG) and may provide predictive and prognostic parameters. Response assessment criteria are still an unmet need and new theranostic pairs showed preliminary encouraging results. PRRT for NET has become a paradigm of modern theranostics. PRRT holds a favorable toxicity profile, and it is associated with a prolonged time to progression, reduction of symptoms, and improved patients' quality of life. In light of further optimization, different new strategies have been investigated, along with the development of new radiopharmaceuticals.

Radioiodine whole body scan pitfalls in differentiated thyroid cancer.

PURPOSE: whole body scan (WBS) performed following diagnostic or therapeutic administration of I-131 is useful in patients with differentiated thyroid carcinoma. However, it can be falsely positive in various circumstances. We aimed to report a series of pitfalls in a clinical perspective. METHODS: A search in the database PubMed utilizing the following terms: "false radioiodine uptake" and "false positive iodine 131 scan" has been made in January 2023. Among the 346 studies screened, 230 were included in this review, with a total of 370 cases collected. Physiological uptakes were excluded. For each patient, sex, age, dose of I-131 administered, region and specific organ of uptake and cause of false uptake were evaluated. RESULTS: 370 cases of false radioiodine uptake were reported, 19.1% in the head-neck region, 34.2% in the chest, 14.8% in the abdomen, 20.8% in the pelvis, and 11.1% in the soft tissues and skeletal system. The origin of false radioiodine uptake was referred to non-tumoral diseases in 205/370 cases (55.1%), benign tumors in 108/370 cases (29.5%), malignant tumors in 25/370 cases (6.7%), and other causes in 32/370 cases (8.7%). CONCLUSIONS: WBS is useful in the follow-up of patients with differentiated thyroid carcinoma, however it can be falsely positive in various circumstances. For this reason, it is critically important to correlate the scintigraphic result with patient's medical history, serum thyroglobulin levels, additional imaging studies and cytologic and/or histologic result.

State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

ABSTRACT: Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

Guiding principles on the education and practice of theranostics.

PURPOSE: The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists. METHODS: To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice. RESULTS: Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries. CONCLUSION: The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics.

Real-Life Use of [68Ga]Ga-DOTANOC PET/CT in Confirmed and Suspected NETs from a Prospective 5-Year Electronic Archive at an ENETS Center of Excellence: More Than 2000 Scans in More Than 1500 Patients.

The recent introduction of novel treatments for advanced neuroendocrine tumors (NETs) and the well-established impact of clinical case discussion within dedicated multidisciplinary teams indicates the need to promote the centralization of rare diseases, such as NENs (neuroendocrine neoplasms). Data on the real-life use of and indications for [68Ga]Ga-DOTANOC PET/CT were collected from a prospective monocentric 5-year electronic archive including consecutive patients with confirmed and suspected NETs (September 2017 to May 2022). Overall, 2082 [68Ga]Ga-DOTANOC PET/CT scans (1685 confirmed NETs, 397 suspected NETs) were performed in 1537 patients. A high positivity rate was observed across different clinical settings (approximately 70%). Approximately 910/2082 scans were requested by the local oncology ward (851 confirmed NETs, 59 suspected NETs). The following observations were found: (i) the detection rate across all indications was 73.2% (higher for staging, peptide receptor radioligand therapy (PRRT) selection, and treatment response assessment); (ii) in suspected NETs, PET was more often positive when based on radiological findings. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the global trends in the use of [68Ga]Ga-DOTANOC PET/CT for different clinical indications and primary tumor sites, but prompts the need for further multicenter data sharing in such a rare and slowly progressive disease setting.

European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer.

BACKGROUND: In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications. OBJECTIVE: We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa. DESIGN, SETTING, AND PARTICIPANTS: The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores. RESULTS AND LIMITATIONS: After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [177Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [223Ra]RaCl2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [18F]FDG and PSMA PET prior to [177Lu]Lu-PSMA therapy. CONCLUSIONS: There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community. PATIENT SUMMARY: There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy.

AIM: The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding. METHODS: This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes. RESULTS: Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20-46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS. CONCLUSION: Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.