The Journal of Nuclear Medicine最新文献

The Pelvic Rosetta Classification (PRC) project aimed to develop an interdisciplinary, landmark-based pelvic lymph node map for patients with prostate cancer to improve communication between imaging specialists and urologists. Methods: After an intense development phase, we conducted 3 evaluation rounds including 19 clinical experts having consensus meetings after each evaluation round. Experts contoured lymph node areas (LNA) for 2 patients with prostate cancer. Contours were assessed qualitatively and quantitatively. The PRC was further validated by assignment of 30 prostate-specific membrane antigen PET/CT–positive lesions to LNAs. The interrater reliability was calculated using Fleiss κ. Based on the final PRC, a complete contour and a 3-dimensional model were created. Results: Eight pelvic (external iliac, cranial/caudal obturator fossa, dorsal internal iliac, vesico-prostatic pedicle, mesorectal/perirectal, presacral, preprostatic/retropubic) and 4 extrapelvic (common iliac, intercommon, sigmoid, inguinal) LNAs were defined using anatomic landmarks which are consistently recognizable on imaging and intraoperatively. Strong consensus between experts existed for smaller, well-defined LNAs (e.g., preprostatic/retropubic, mesorectal/perirectal LNAs) compared with regions with proportionally large borders (e.g., obturator fossa, vesico-prostatic pedicle LNAs). Overall, moderate agreement (κ = 0.53) was observed during validation. Discrepancies were mostly encountered for lesions adjacent to borders between LNAs. The final contour and 3-dimensional model were approved by all experts. Conclusion: The PRC project showed fair reproducibility and validity. Further external validation is needed to assess its influence on interdisciplinary communication and treatment outcomes.

High expression of prostate-specific membrane antigen (PSMA) is not limited to prostate cancer but can be found in other tumor entities, such as hepatocellular carcinoma (HCC), and could possibly be used for theranostic purposes. Our aim was to investigate the diagnostic potential of the hepatobiliary excreted radiotracer [¹⁸F]PSMA-1007 on initial staging of HCC. Methods: This prospective clinical study (NCT05547919) included 10 participants (9 men, 1 woman) with treatment-naïve, histopathologically proven PSMA-positive HCC. All participants underwent [¹⁸F]PSMA-1007 PET with unenhanced low-dose CT. All scans were analyzed visually and quantitatively. We assessed the SUV_max of the primary tumor and the SUV_mean of nonaffected liver parenchyma and calculated tumor-to-background ratios (i.e., SUV_max HCC/SUV_mean liver) for each patient. In addition, we assessed possible eligibility for PSMA-directed radiopharmaceutical therapy according to the PROMISE criteria. The presence of local lymph nodes and distant metastases was noted for [¹⁸F]PSMA-1007 PET/CT and compared with the results of contrast-enhanced CT of the trunk and MRI of the upper abdomen. Possible prognostic implications of PSMA expression on immunohistochemistry and on [¹⁸F]PSMA-1007 PET/CT were compared with progression-free survival (defined as clinical progression, radiographic progression, or death from any cause) using Cox regression. Results: [¹⁸F]PSMA-1007 PET showed high uptake in 7 of 10 patients (PROMISE score 2, n = 4; PROMISE score 3, n = 3); mediocre or missing uptake was found in 3 participants (PROMISE score 0, n = 1; PROMISE score 1, n = 2). The median tumor-to-background ratio was 2.7 (interquartile range, 2.65). [¹⁸F]PSMA-1007 PET did not reveal new distant metastatic lesions compared with contrast-enhanced CT. In 1 patient, local lymph node metastases were considered PSMA-negative despite high uptake in the primary tumor. Whether assessed ex vivo or in vivo, PSMA expression did not correlate with progression-free survival. Conclusion: [¹⁸F]PSMA-1007 can be used depict untreated HCC and shows high uptake relative to background, indicative of excellent image contrast. High tracer accumulation in 70% of the participants suggests a possible use for PSMA-directed radiopharmaceutical therapy in an end-stage setting. However, PSMA expression was not prognostic for outcome, possibly because of the small sample size.

⁶⁸Ga-PSMA-11 PET/CT (PSMA PET/CT) is used for staging advanced prostate cancer (PCa); however, its role in initial cancer detection and guiding localized treatment remains uncertain. The primary objective of this study was to assess the impact of upfront PSMA PET/CT on treatment decision-making based on imaging and biopsy-derived information. Methods: In this prospective, phase 2 interventional trial, 230 biopsy- and imaging-naïve men with suspected PCa underwent PSMA PET/CT and multiparametric MRI (mpMRI) before targeted ultrasound fusion and systematic biopsy. Randomized assessor teams independently reviewed histopathology and imaging data from either the mpMRI or the combined mpMRI plus PSMA PET/CT pathway and formulated treatment plans accordingly. Patient recruitment was conducted between 2021 and 2023. Results: Among 137 patients with PCa (9% low-, 35% intermediate-, and 15% high-risk disease), PSMA PET/CT altered management plans in 34% of patients, primarily modifying local treatment strategies, including lymph node dissection (16%), a nerve-sparing procedure (18%), and radiation field adjustments (28%). Systemic therapy escalation was rare (1%). In addition, 2% of patients initiated active treatment, 5% received adjunctive hormone therapy, and 7% underwent metastasis-directed therapy. Upfront PSMA PET/CT prompted treatment intensification at comparable rates in both intermediate-risk (31%) and high-risk (30%) PCa with high interrater agreement (Cohen κ, 0.71; 95% CI, 0.61–0.80). Prostate-specific antigen density of at least 0.15 ng/mL³ (odds ratio, 2.48; 95% CI, 1.22–5.06) and abnormal digital rectal examination (odds ratio, 2.12; 95% CI, 1.03–4.33) predicted PSMA PET/CT–driven changes. Conclusion: Early PSMA PET/CT staging altered treatment strategies for up to one third of patients with intermediate- and high-risk PCa by enhancing metastasis detection and local tumor characterization. Its effect on oncologic and functional outcomes warrants further investigation.

Artificial intelligence–generated content (AIGC) has shown remarkable performance in nuclear medicine imaging (NMI), offering cost-effective software solutions for tasks such as image enhancement, motion correction, and attenuation correction. However, these advancements come with the risk of hallucinations, generating realistic yet factually incorrect content. Hallucinations can misrepresent anatomic and functional information, compromising diagnostic accuracy and clinical trust. This paper presents a comprehensive perspective on hallucination-related challenges in AIGC for NMI, introducing the DREAM report, which covers recommendations for definition, representative examples, detection and evaluation metrics, and attributions and mitigation strategies. This position statement paper aims to initiate a common understanding for discussions and future research toward enhancing AIGC applications in NMI, thereby supporting their safe and effective deployment in clinical practice.

Continuation of effective and well-tolerated systemic treatment is often performed in care for metastatic castration-resistant prostate cancer. Likewise, continued administration of [¹⁷⁷Lu]Lu-PSMA radiopharmaceutical therapy beyond the approved number of cycles holds promising potential to enhance therapeutic efficacy. Rechallenge therapy involves readministration of [¹⁷⁷Lu]Lu-PSMA cycles after a break, whereas extended therapy continues treatment beyond the standard 6 cycles without interruption. Both approaches aim to improve disease control and prolong survival in patients with metastatic castration-resistant prostate cancer. However, practices vary: some clinicians continue treatment in patients with early favorable responses, whereas others recommend pausing therapy after significant prostate-specific antigen declines, even after a few cycles. In this narrative review, we show that safety profiles for continued [¹⁷⁷Lu]Lu-PSMA radiopharmaceutical therapy are generally favorable, and most adverse events are mild to moderate in severity. Hematotoxicity, particularly anemia and thrombocytopenia, is the most significant concern, with few patients experiencing high-grade adverse events. In addition, cumulative irradiation, particularly during extended therapy, necessitates careful monitoring of hematologic and renal function. Biochemical responses to rechallenge and extended [¹⁷⁷Lu]Lu-PSMA therapy are promising, with at least 50% reductions in prostate-specific antigen levels observed in a significant proportion of highly selected patients. Moreover, survival outcomes are encouraging, showing the extension of overall and progression-free survival beyond the known data for standard therapy. Despite these advances, challenges remain in optimizing patient selection, managing cumulative toxicities, and harmonizing treatment protocols. In addition, variability in trial designs, influenced by international regulatory differences, limits the current evidence and necessitates consideration of each treatment approach within its regulatory context. Prospective studies are needed to refine therapeutic strategies, implement consistent clinical and imaging response criteria, and identify predictive biomarkers to improve both efficacy and safety.

Nonuniform radiopharmaceutical uptake in kidney tissues leads to substructure-level absorbed dose heterogeneity, confounding the establishment of absorbed dose–effect relationships for nephrotoxicity in radiopharmaceutical therapy. We developed a model to enable nephron-level dosimetry. Methods: A multinephron computational model was developed on the basis of 3-dimensional multiphoton microscopy data, including different nephron types (superficial, midcortical, and juxtamedullary) and their main substructures (glomerulus, proximal tubule [PT], and distal tubule) in kidney tissues. Nephron-level S values were determined using Monte Carlo calculations for several β⁻- and α-emitting radionuclides. The multinephron dosimetry framework was applied to nonuniform kidney tissue uptake data on ²²⁵Ac, located primarily in midcortical and juxtamedullary PTs. Results: A nonuniform substructure activity distribution resulted in pronounced absorbed dose heterogeneities. S values varied substantially among nephron types, with the largest in juxtamedullary substructures. The self-dose to PTs was 7.6–15 times higher than the S value of superficial PTs for the α-emitters considered. The cross dose to juxtamedullary glomeruli was on average 20% higher than to superficial glomeruli. The case study revealed substantial absorbed dose heterogeneity, with the absorbed dose to the different PTs being 40%–73% higher than to their respective glomeruli. Additionally, the contribution of free ²¹³Bi to the total absorbed dose differed from that of ²²⁵Ac. Conclusion: The developed multinephron framework enables nephron-level dosimetry, allowing quantification of absorbed dose heterogeneity within renal tissues. Such insights enable establishing critical nephron substructures for nephrotoxicity in radiopharmaceutical therapy, supporting nephroprotective strategies during clinical translation of novel radiopharmaceuticals.

Although tumor volume and new lesions (NLs) have been investigated previously as measures of response, the clinical impact of changes in tumor uptake on prostate-specific membrane antigen (PSMA) PET remains largely unknown. Methods: This multicenter retrospective study investigated the clinical impact of changes in tumor uptake and volume on PSMA PET during [¹⁷⁷Lu]Lu-PSMA in metastatic castration-resistant prostate cancer (mCRPC). The primary outcomes were the associations of changes in SUV_max (ΔSUV_max) and SUV_mean (ΔSUV_mean), changes in total tumor volume (ΔTTV), and occurrence of NLs with prostate-specific antigen (PSA) progression-free survival (PSA-PFS) and overall survival (OS). The study included patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA between 2014 and 2019. PSMA PET/CT was performed at baseline and after 2 cycles of therapy. Whole-body analyses (SUV_max, SUV_mean, TTV, and NLs) were performed and calculated using qPSMA software. Results: In total, 124 patients with mCRPC (median age, 73 y; interquartile range, 67–76 y) were included in the study. Whole-body ΔTTV and the occurrence of NLs were significantly associated with shorter PSA-PFS (hazard ratio [HR], 5.7; 95% CI, 3.59–9.06; and HR, 1.6; 95% CI, 1.4–1.8; P < 0.0001) and with OS (HR, 2.3; 95% CI, 1.61–3.43; and HR, 1.3; 95% CI, 1.1–1.4; P < 0.001). Patient-based analysis showed that ΔSUV_max and ΔSUV_mean were not associated with outcome (HR, 1.00; 95% CI, 0.99–1.00; P = 0.30; and HR, 0.90; 95% CI, 0.99–1.00; P = 0.11). Region-based analysis found that only ΔSUV_max in visceral lesions was significantly associated with PSA-PFS (P = 0.007) but not with OS. Conclusion: Only ΔTTV and the occurrence of NLs provided significant prognostic value and should be considered when evaluating treatment response to [¹⁷⁷Lu]Lu-PSMA therapy.

PET/CT using ⁶⁸Ga-labeled fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) may detect occult metastases and identify aggressive tumor biology in patients with pancreatic ductal adenocarcinoma (PDAC). We evaluated the impact of ⁶⁸Ga-FAPI PET/CT on surgical treatment in this patient population. Methods: Patients with PDAC who were deemed operative candidates after standard CT underwent pretreatment ⁶⁸Ga-FAPI PET/CT and were followed until confirmation of treatment intent. Lymph node ratio in resected tumors was used as a surrogate marker for tumor biology and correlated with the SUV_max of the primary tumor using linear regression. Results: Of 16 eligible participants, 5 (31%) had metastases that were not visible on CT scans but were detected with ⁶⁸Ga-FAPI PET/CT, and surgery was prevented. No additional investigations were prompted by ⁶⁸Ga-FAPI PET/CT unless they changed treatment intent. Two participants without metastases on ⁶⁸Ga-FAPI PET/CT did not have surgery because of local progression after neoadjuvant therapy. The SUV_max of the primary tumor at 60 min correlated with the lymph node ratio in resected PDAC (P = 0.04). Conclusion: ⁶⁸Ga-FAPI PET/CT may enhance treatment selection in PDAC. Comparative trials are the next step to confirm role in the clinical setting.