Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2.

Background: Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature. Materials and Methods: The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators. Results: This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1/2 mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non-BRCA1/2 mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies. Conclusions: The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state.

Expert Perspectives on Controversies in Castration-Sensitive Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 1.

Purpose: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC. Materials and Methods: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy. Results: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC. Conclusions: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC.

Prostate-specific Membrane Antigen: Interpretation Criteria, Standardized Reporting, and the Use of Machine Learning.

Prostate-specific membrane antigen targeting positron emission tomography (PSMA-PET) is routinely used for the staging and restaging of patients with various stages of prostate cancer. For clear communication with referring physicians and to improve inter-reader agreement, the use of standardized reporting templates is mandatory. Increasingly, tumor volume is used by reporting and response assessment frameworks to prognosticate patient outcome or measure response to therapy. However, the quantification of tumor volume is often too time-consuming in routine clinical practice. Machine learning-based tools can facilitate the quantification of tumor volume for improved outcome prognostication.

Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617. METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1-4.9 h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates. RESULTS: 56 patients (means age 76.2 ± 8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS. CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

Gastrin Releasing Peptide Receptors-targeted PET Diagnostics and Radionuclide Therapy for Prostate Cancer Management: Preclinical and Clinical Developments of the Past 5 Years.

Each tumor has its own distinctive molecular identity. Treatment, therefore, should be tailored to this unique cancer phenotype. Theragnostics uses the same compound for targeted imaging and treatment, radiolabeled to an appropriate radionuclide, respectively. Gastrin-releasing peptide receptors (GRPRs) are overexpressed in prostate cancer, and radiolabeled GRPR antagonists have shown high diagnostic performance at staging and biochemical recurrence. Several GRPR-targeting theragnostic compounds have been developed preclinically. Their translation into clinics is underway with 4 clinical trials recruiting participants with GRPR-expressing tumors.

Prospective Comparison of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI in Patients with Biochemically Recurrent Prostate Cancer.

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in prostate cancer (PC) but may provide complementary information.68Ga-PSMA-R2 and 68Ga-NeoB (DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-NH-CH[CH2-CH(CH3)2]2) are novel PET radiopharmaceuticals that were developed for theranostic use. In this phase II imaging study, we assessed the feasibility, safety, and diagnostic performance of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI for detection of biochemically recurrent PC. Methods: We prospectively enrolled 27 men with suspected biochemically recurrent PC after initial treatment but noncontributory conventional imaging results (negative or equivocal findings on MRI, CT, and/or bone scan). Participants underwent 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI within 2 wk in noncontrolled order. The SUVmax of putative PC lesions was measured and compared with a composite reference standard (histopathology, follow-up imaging, prostate-specific antigen change). The SUVmax and SUVmean of background organs were measured. Vital signs were recorded before injection of the radiopharmaceuticals and after the scans. Adverse events were recorded up to 72 h after each scan. Results: The prostate-specific antigen level at enrollment was 3.5 ± 3.9 ng/mL (range, 0.3-13.5 ng/mL). 68Ga-NeoB PET/MRI detected 31 lesions in 18 patients (66.7%), whereas 68Ga-PSMA-R2 identified 20 lesions in 15 participants (55.6%). 68Ga-NeoB PET/MRI showed higher sensitivity (85.7% vs. 71.4%), accuracy (88.9% vs. 77.8%), and negative predictive value (66.7% vs. 50.0%) than 68Ga-PSMA-R2, whereas specificity and positive predictive value were equally high (100.0% for both). In 6 patients, 68Ga-NeoB PET/MRI identified 14 lesions that were false-negative on 68Ga-PSMA-R2 PET/MRI. The mean lesion SUVmax was 6.6 ± 3.2 (range, 2.9-13.2) for 68Ga-NeoB and 4.4 ± 1.5 (range, 2.6-8.8) for 68Ga-PSMA-R2 (P = 0.019). Overall lower uptake was noted in tumors and background organs for 68Ga-PSMA-R2. There were no significant changes in vital signs before and after the scans. No adverse events were reported in the 72-h period after scans. Conclusion: 68Ga-NeoB and 68Ga-PSMA-R2 are safe for diagnostic imaging. 68Ga-NeoB PET/MRI showed better diagnostic performance than 68Ga-PSMA-R2. 68Ga-PSMA-R2 showed overall lower uptake, equally in background organs and tumors, and might therefore not be an ideal theranostic compound. Further evaluation in larger cohorts is needed to confirm our preliminary data.

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.

Molecular Imaging in Soft-tissue Sarcoma: Evolving Role of FDG PET.

Soft tissue sarcomas are a rare and heterogenous group of tumors that account for 2% of all cancer-related deaths. Molecular imaging with FDG PET can offer valuable metabolic information to help inform clinical management of soft tissue sarcomas that is unique and complementary to conventional diagnostic imaging techniques. FDG PET imaging often correlates with tumor grade, can help guide biopsy, and frequently detects additional sites of disease compared to conventional imaging in patients being considered for definitive or salvage therapy. Traditional size-based evaluation of treatment response is often inadequate in soft tissue sarcoma and changes in metabolic activity can add significant value to interim and end of treatment imaging for high-grade sarcomas. FDG PET can be used for detection of recurrence or malignant transformation and thus play a vital role in surveillance. This article reviews the evolving role of FDG PET in initial diagnosis, staging, treatment response assessment, and restaging. Further studies on the use of FDG PET in soft sarcoma are needed, particularly for rare histopathologic subtypes.

68Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial.

BACKGROUND: National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer. METHODS: This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete. FINDINGS: Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported. INTERPRETATION: 68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients. FUNDING: The US Department of Defense.

Nuclear Medicine and Molecular Imaging Applications in Gynecologic Malignancies: A Comprehensive Review.

Gynecologic malignancies, consisting of endometrial, cervical, ovarian, vulvar, and vaginal cancers, pose significant diagnostic and management challenges due to their complex anatomic location and potential for rapid progression. These tumors cause substantial morbidity and mortality, often because of their delayed diagnosis and treatment. An estimated 19% of newly diagnosed cancers among women are gynecologic in origin. In recent years, there has been growing evidence supporting the integration of nuclear medicine imaging modalities in the diagnostic work-up and management of gynecologic cancers. The sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) combined with the anatomical specificity of computed tomography (CT) and magnetic resonance imaging (MRI) allows for the hybrid evaluation of metabolic activity and structural abnormalities that has become an indispensable tool in oncologic imaging. Lymphoscintigraphy, using technetium 99m (99mTc) based radiotracers along with single photon emission computed tomography/ computed tomography (SPECT/CT), holds a vital role in the identification of sentinel lymph nodes to minimize the surgical morbidity from extensive lymph node dissections. While not yet standard for gynecologic malignancies, promising therapeutic nuclear medicine agents serve as specialized treatment options for patients with advanced or recurrent disease. This article aims to provide a comprehensive review on the nuclear medicine applications in gynecologic malignancies through the following objectives: 1) To describe the role of nuclear medicine in the initial staging, lymph node mapping, response assessment, and recurrence/surveillance imaging of common gynecologic cancers, 2) To review the limitations of 18F-FDG PET/CT and promising applications of 18F-FDG PET/MRI in gynecologic malignancy, 3) To underscore the promising theragnostic applications of nuclear medicine, 4) To highlight the current role of nuclear medicine imaging in gynecologic cancers as per the National Comprehensive Cancer Network (NCCN), European Society of Surgical Oncology (ESGO), and European Society of Medical Oncology (ESMO) guidelines.

Spatial transcriptomic analysis drives PET imaging of tight junction protein expression in pancreatic cancer theranostics.

We apply spatial transcriptomics and proteomics to select pancreatic cancer surface receptor targets for molecular imaging and theranostics using an approach that can be applied to many cancers. Selected cancer surfaceome epithelial markers were spatially correlated and provided specific cancer localization, whereas the spatial correlation between cancer markers and immune- cell or fibroblast markers was low. While molecular imaging of cancer-associated fibroblasts and integrins has been proposed for pancreatic cancer, our data point to the tight junction protein claudin-4 as a theranostic target. Claudin-4 expression increased ∼16 fold in cancer as compared with normal pancreas, and the tight junction localization conferred low background for imaging in normal tissue. We developed a peptide-based molecular imaging agent targeted to claudin-4 with accumulation to ∼25% injected activity per cc (IA/cc) in metastases and ∼18% IA/cc in tumors. Our work motivates a new approach for data-driven selection of molecular targets.

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.

PSMA PET for Detection of Recurrence.

Prostate cancer (PC) is a significant health concern worldwide, with high incidence and mortality rates. Early and accurate detection and localization of recurrent disease at biochemical recurrence (BCR) is critical for guiding subsequent therapeutic decisions and improving patient outcomes. At BCR, conventional imaging consisting of CT, MRI, and bone scintigraphy are recommended by US and European guidelines, however, these modalities all bear certain limitations in detecting metastatic disease, particularly in low-volume relapse at low prostate-specific antigen (PSA) levels. Molecular imaging with PET/CT or PET/MRI using prostate-specific membrane antigen (PSMA) targeting radiopharmaceuticals has revolutionized imaging of PC. Particularly at BCR PC, PSMA PET has shown better diagnostic performance compared to conventional imaging in detecting local relapse and metastases, even at very low PSA levels. The most recent version of the National Comprehensive Cancer Network (NCCN) guideline has included PSMA-targeted PET/CT or PET/MRI for the localization of BCR PC. There are several different PSMA-targeting radiopharmaceuticals labeled with different radioisotopes, each with slightly different characteristics, but overall similar high sensitivity and specificity for PC. PSMA-targeted PET has the potential to significantly impact patient care by guiding personalized treatment decisions and thus improving outcomes in BCR PC patients.

International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology.

PREAMBLE: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging. The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI, the ISMRM, and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Modified PROMISE criteria for standardized interpretation of gastrin-releasing peptide receptor (GRPR)-targeted PET.

PURPOSE: There are image interpretation criteria to standardize reporting prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET). As up to 10% of prostate cancer (PC) do not express PSMA, other targets such as gastrin-releasing peptide receptor (GRPR) are evaluated. Research on GRPR-targeted imaging has been slowly increasing in usage at staging and biochemical recurrence (BCR) of PC. We therefore propose a modification of the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria (mPROMISE) for GRPR-targeted PET. METHODS: [68 Ga]Ga-RM2 PET data from initially prospective studies performed at our institution were retrospectively reviewed: 44 patients were imaged for staging and 100 patients for BCR PC. Two nuclear medicine physicians independently evaluated PET according to the mPROMISE criteria. A third expert reader served as standard reference. Interreader reliability was computed for GRPR expression, prostate bed (T), lymph node (N), skeleton (Mb), organ (Mc) metastases, and final judgment of the scan. RESULTS: The interrater reliability for GRPR PET at staging was moderate for GRPR expression (0.59; 95% confidence interval [CI] 0.40, 0.78), substantial for T-stage (0.78; 95% CI 0.63, 0.94), and almost perfect for N-stage (0.97; 95% CI 0.92, 1.00) and final judgment (0.92; 95% CI 0.82, 1.00). The interreader agreement at BCR showed substantial agreement for GRPR expression (0.70; 95% CI 0.59, 0.81) and final judgment (0.65; 95% CI 0.53, 0.78), while almost perfect agreement was seen across the major categories (T, N, Mb, Mc). Acceptable performance of the mPROMISE criteria was found for all subsets when compared to the standard reference. CONCLUSION: Interpreting GRPR-targeted PET using the mPROMISE criteria showed its reliability with substantial or almost perfect interrater agreement across all major categories. The proposed modification of the PROMISE criteria will aid clinicians in decreasing the level of uncertainty, and clinical trials to achieve uniform evaluation, reporting, and comparability of GRPR-targeted PET. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03113617 and NCT02624518.

2022 SNMMI Highlights Lecture: General Nuclear Medicine.

The Highlights Lectures at the closing sessions of SNMMI Annual Meetings were originated and presented for more than 30 y by Henry N. Wagner, Jr., MD. Beginning in 2010, the duties of summarizing selected significant presentations at the meeting were divided annually among 4 distinguished nuclear and molecular medicine subject matter experts. The 2022 Highlights Lectures were delivered on June 14 at the SNMMI Annual Meeting in Vancouver, Canada. This month we feature the lecture by Andrei Iagaru, MD, Professor of Radiology-Nuclear Medicine at Stanford University School of Medicine (CA) and Chief of the Division of Nuclear Medicine and Molecular Imaging at Stanford HealthCare, who spoke on general nuclear medicine highlights from the meeting. Note that in the following presentation summary, numerals in brackets represent abstract numbers as published in The Journal of Nuclear Medicine (2022;63[suppl 2]).

SPECT at the speed of PET: a feasibility study of CZT-based whole-body SPECT/CT in the post 177Lu-DOTATATE and 177Lu-PSMA617 setting.

PURPOSE: To evaluate the feasibility of using the StarGuide (General Electric Healthcare, Haifa, Israel), a new generation multi-detector cadmium-zinc-telluride (CZT)-based SPECT/CT, for whole-body imaging in the setting of post-therapy imaging of 177Lu-labeled radiopharmaceuticals. METHODS: Thirty-one patients (34-89 years old; mean ± SD, 65.5 ± 12.1) who were treated with either 177Lu-DOTATATE (n=17) or 177Lu-PSMA617 (n=14) as part of standard of care were scanned post-therapy with the StarGuide; some were also scanned with the standard GE Discovery 670 Pro SPECT/CT. All patients had either 64Cu-DOTATATE or 18F-DCFPyL PET/CT prior to first cycle of therapy for eligibility check. The detection/targeting rate (lesion uptake greater than blood pool uptake) of large lesions meeting RECIST 1.1 size criteria on post-therapy StarGuide SPECT/CT was evaluated and compared to the standard design GE Discovery 670 Pro SPECT/CT (when available) and pre-therapy PET by two nuclear medicine physicians with consensus read. RESULTS: This retrospective analysis identified a total of 50 post-therapy scans performed with the new imaging protocol from November 2021 to August 2022. The StarGuide system acquired vertex to mid-thighs post-therapy SPECT/CT scans with 4 bed positions, 3 min/bed and a total scan time of 12 min. In comparison, the standard GE Discovery 670 Pro SPECT/CT system typically acquires images in 2 bed positions covering the chest, abdomen, and pelvis with a total scan time of 32 min. The pre-therapy 64Cu-DOTATATE PET takes 20 min with 4 bed positions on GE Discovery MI PET/CT, and 18F-DCFPyL PET takes 8-10 min with 4-5 bed positions on GE Discovery MI PET/CT. This preliminary evaluation showed that the post-therapy scans acquired with faster scanning time using StarGuide system had comparable detection/targeting rate compared to the Discovery 670 Pro SPECT/CT system and detected large lesions defined by RECIST criteria on the pre-therapy PET scans. CONCLUSION: Fast acquisition of whole-body post-therapy SPECT/CT is feasible with the new StarGuide system. Short scanning time improves the patients' clinical experience and compliance which may lead to increased adoption of post-therapy SPECT. This opens the possibility to offer imaged-based treatment response assessment and personalized dosimetry to patients referred for targeted radionuclide therapies.

Neuroendocrine Tumor Diagnosis: PET/MR Imaging.

Imaging plays a critical role in the diagnosis and management of neuroendocrine tumors (NETs). The initial workup of the primary tumor, including its characterization, local and distant staging, defines subsequent treatment decisions. Functional imaging using hybrid systems, such as PET combined with computed tomography, has become the gold standard. As NETs majorly arise from the gastrointestinal system and metastasize primarily to the liver, simultaneous PET and MR imaging with its high soft tissue contrast might be a valuable clinical one-stop-shop whole-body imaging tool. This review presents the current status and challenges of PET/MR imaging for diagnosis of NETs.