The Journal of Nuclear Medicine最新文献

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.

Anatomic imaging of renal masses provides limited information on the histology or likely aggressiveness of the tumor, leading to the use of invasive procedures such as renal mass biopsy or empiric partial or radical nephrectomy. Molecular imaging can assist in risk stratification of indeterminate renal masses, potentially contributing to optimal patient decision-making. Two primary approaches have been explored for renal mass molecular imaging. The first is the use of agents that target carbonic anhydrase IX (CAIX), a cell-surface protein that is over-expressed on clear cell renal cell carcinoma (ccRCC) and generally not expressed on other renal tumors. A recent phase III trial (ZIRCON) is widely believed to have laid the groundwork for United States Food and Drug Administration approval of the CAIX monoclonal antibody ⁸⁹Zr-girentuximab. The second approach is the use of mitochondrial imaging agents, most notably ^99mTc-sestamibi, which are lipophilic cations that accumulate in tumors with an abundance of mitochondria with negative charge potential (e.g., oncocytomas and other benign/indolent lesion) and do not accumulate in tumors with multidrug resistance pumps (e.g., ccRCC). The complementary information from ⁸⁹Zr-girentuximab and ^99mTc-sestamibi can provide improved risk stratification. Further, emerging new targeted radiotracers and techniques such as imaging biomarker discovery with artificial intelligence will bolster those concepts. In this manual, we synthesize key data into a recommended approach.

[¹⁷⁷Lu]Lu-PSMA-617 radiopharmaceutical therapy improves survival and quality of life in patients with metastatic castration-resistant prostate cancer. We assessed whether patients who did not achieve an early prostate-specific antigen (PSA) decline after the first cycle (C1) benefited from further [¹⁷⁷Lu]Lu-PSMA-617. Methods: We analyzed patients with metastatic castration-resistant prostate cancer participating in a registry of [¹⁷⁷Lu]Lu-PSMA-617 (ProsTIC registry, NCT04769817). Patients with a PSA either rising (≥25% increase from baseline) or stable (30% decrease to 25% increase from baseline) within 28 d of starting treatment (C1) and consequently received a second dose (cycle 2) were included. Biochemical response was defined as a PSA decline of more than 50% from baseline (PSA-50) within 20 wk after C1. Quality of life was assessed on 2 validated scales. We evaluated the effect of PSA change and 3 imaging parameters (pretreatment PSMA PET SUV_mean, pretreatment [¹⁸F]FDG PET metabolic tumor volume, and mean total tumor dosimetry on SPECT/CT after C1) with these outcomes and survival time after cycle 2. Results: Of 195 patients, 103 met inclusion criteria between January 5, 2021, and March 30, 2023, with an early PSA rise in 31 patients (30%) or stable PSA in 72 patients (70%). Of 103 patients, 45 (44%) achieved PSA-50 by 140 d after C1. Seven of 31 patients (23%) and 38 of 72 patients (53%) with early rising and stable PSA, respectively, had achieved a PSA-50 by 140 d after C1. A PSMA SUV_mean of 10 or more versus an SUV_mean of less than 10 conferred a higher chance of PSA-50 (59% vs. 37%; odds ratio, 2.53; 95% CI, 1.08–5.95). In total, 59 deaths were recorded with a median overall survival of 11.3 mo after cycle 2. [¹⁸F]FDG metabolic tumor volume was the only variable to have a meaningful association with overall survival. Patients with baseline pain scores of 10 or greater according to EORTC QLQ-C30 pain or 2 or greater according to BPI-SF had clinically meaningful reductions in pain in 39 of 55 patients (71%) and 17 of 37 patients (46%), respectively. Conclusion: Discontinuing [¹⁷⁷Lu]Lu-PSMA-617 based solely on PSA response after just 1 cycle is not advisable as a substantial number of patients achieve PSA-50 or a reduction in pain. Baseline imaging parameters have prognostic utility and can assist in patient counseling and clinical decision-making.

The combination of external-beam radiotherapy (EBRT) and ¹⁷⁷Lu-labeled prostate-specific membrane antigen (PSMA) ligands may improve the outcome for specific prostate cancer indications. This review aims to introduce the concept of this combined treatment, provide an overview of preclinical and clinical studies (as well as ongoing trials), and address current challenges and future directions to investigate this emerging therapeutic approach. Methods: A comprehensive search was conducted in online research databases (including PubMed) and trial databases (including ClinicalTrials.gov) to gather all relevant preclinical and clinical studies and ongoing trials on the combination of EBRT and ¹⁷⁷Lu-labeled PSMA ligands. Results: One completed preclinical study demonstrated increased tumor growth delay and survival with combined EBRT and [¹⁷⁷Lu]Lu-PSMA-617, compared with monotherapies, and one an additive effect. Four clinical reports published results on this combination, including series showing tumor regression in metastatic lesions and a pilot study demonstrating an increased biologically effective dose. Ten ongoing prospective clinical trials with varying designs, patient populations (de novo oligometastatic, oligorecurrent, and locally recurrent), treatment schedules ([¹⁷⁷Lu]Lu-PSMA ligands neoadjuvant, adjuvant, concurrent with EBRT), and radiation doses and fractionation schemes were identified. Conclusion: The combination of EBRT and [¹⁷⁷Lu]Lu-PSMA ligands holds promise to improve tumor control without increasing toxicity across various stages of prostate cancer. However, optimal treatment scheduling, dosing regimens, the role of dosimetry, and specific clinical indications require further investigation through robust preclinical and clinical research to guide future clinical trials.

Peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE is an approved treatment for metastatic neuroendocrine tumors (NETs). Although the therapy is effective, hematologic toxicity, particularly leukopenia, remains a significant concern. The spleen, which accumulates radiolabeled somatostatin analogs, may play a critical role in modulating this toxicity. This study investigates whether patients undergoing PRRT after splenectomy exhibit lower hematologic toxicity. Methods: This multicenter retrospective study included 68 patients with metastatic NETs treated with PRRT between 2009 and 2022. Splenectomized patients (n = 34) were matched to nonsplenectomized patients on the basis of age, sex, tumor location, grading, metastatic pattern, and treatment cycles. Hematologic parameters (leukocytes, lymphocytes, neutrophils, hemoglobin, and platelets) were assessed at baseline and 12 and 24 mo after PRRT. Hematotoxicity was graded using Common Terminology Criteria for Adverse Events. Statistical analyses included t test, Mann–Whitney U test, and Fisher exact test, with an α of 0.05 and Bonferroni adjustment applied. Results: Splenectomized patients had significantly lower rates of leukopenia, with a mean decline of 12.8% in leukocyte count at 24 mo versus 47.2% in nonsplenectomized patients (P < 0.001), and a higher median absolute leukocyte count (7.2 vs. 4.2 × 10³/mm³, P < 0.001). Leukopenia occurred in 2 splenectomized patients compared with 20 in the control group (P < 0.001). Lymphocyte decline was also less pronounced, with higher absolute counts at 24 mo. Platelet counts were consistently higher postsplenectomy, although relative changes over time were not significant. Neutrophil counts and hemoglobin levels remained comparable between groups. Conclusion: Splenectomy appears to reduce leukopenia and improve hematologic tolerability in NET patients undergoing PRRT, highlighting the spleen’s role in leukocyte regulation. These patients may better tolerate intensified PRRT regimens, including additional cycles or reinduction, with minimal toxicity. This is particularly relevant for patients with pancreatic NETs, who frequently undergo splenectomy and face a poorer prognosis. Prospective studies are needed to further clarify the spleen’s impact on PRRT-related hematotoxicity and guide treatment optimization.