Journal of nuclear medicine : official publication, Society of Nuclear Medicine最新文献

We aimed to quantitatively investigate the prognostic value of PET-based biomarkers on [¹⁸F]FDG and [⁶⁸Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in patients with highly aggressive neuroendocrine neoplasms (NENs) and to compare the visually assessed differences in uptake on both examinations with progression-free survival (PFS). Methods: In this single-center retrospective analysis, 20 patients with high-grade NENs had undergone [¹⁸F]FDG and [⁶⁸Ga]Ga-FAPI-04 PET. Both PET scans were visually compared, and the presence of [¹⁸F]FDG-positive, [⁶⁸Ga]Ga-FAPI-04-negative (FDG+/FAPI-) lesions was noted. In addition, we assessed maximum, peak, and mean SUV; tumor volume (TV); and total lesion uptake (TLU = TV × SUV_mean) for both radiotracers using a 40% lesion-based threshold. The results of quantitative and visual analysis were correlated with PFS using log-rank analysis or univariate Cox regression. PFS was defined radiographically using RECIST 1.1., clinically using signs of disease progression, or as death. Results: Most primary tumors were located in the gastrointestinal tract (13/20 patients, 65%) or were cancer of unknown primary (5/20 patients, 25%). FDG+/FAPI- lesions were found in 9 of 20 patients (45%). Patients with FDG+/FAPI- lesions had a significantly decreased PFS of 4 mo, compared with 9 mo for patients without FDG+/FAPI- metastases (P = 0.0063 [log-rank test]; hazard ratio [HR], 5.637; 95% CI 1.619-26.16; P = 0.0110 [univariate Cox regression]). On univariate analysis, a significant correlation was also found between PFS and TV for both radiotracers ([¹⁸F]FDG: mean TV, 258 ± 588 cm³; HR, 1.024 [per 10 cm³]; 95% CI, 1.007-1.046; P = 0.0204) ([⁶⁸Ga]Ga-FAPI-04: mean TV, 130 ± 192 cm³; HR, 1.032 [per 10 cm³]; 95% CI, 1.001-1.062; P = 0.0277) and TLU on [¹⁸F]FDG PET (mean TLU, 1,931 ± 4,248 cm³; HR, 1.004 [per 10 cm³]; 95% CI, 1.001-1.007; P = 0.0135). Conclusion: The presence of discordant FDG+/FAPI- lesions is associated with a significantly shorter PFS, which might indicate more aggressive disease prone to early progression. Dual-tracer PET/CT of patients with highly aggressive NENs could help guide treatment decisions or identify high-risk lesions for additional local therapeutic approaches.

It is well known that patients with liver metastasis from metastatic castration-resistant prostate cancer have poor or only transient responses to many forms of systemic therapy. Data on outcomes after treatment with [¹⁷⁷Lu]Lu-PSMA-617 (LuPSMA) are scarce. The VISION trial reports a hazard ratio for overall survival (OS) in the subgroup of patients with liver metastasis without disclosing the absolute duration of survival. Using real-world clinical data, we examined this important subgroup of patients, describing prostate-specific antigen (PSA) response and OS. Methods: A single-institution database was assembled to include all patients receiving LuPSMA at Mayo Clinic in Rochester, Minnesota, for whom treatment was initiated between March 2022 and March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were then categorized by presence or absence of liver metastasis on pretreatment prostate-specific membrane antigen (PSMA) PET. PSA response and OS for the 2 groups (liver metastasis vs. no liver metastasis) were compared using χ² testing and the Kaplan-Meier method, respectively. A multivariate Cox regression analysis was performed, including established prognostic factors. Finally, those with pretreatment circulating tumor DNA as determined in an 83-gene panel were assessed for the presence of pathogenic and likely pathogenic alterations. These findings were summarized using descriptive statistics and compared between the 2 cohorts using the Fisher exact test. Results: The overall cohort consisted of 273 patients, including 43 (15.75%) with liver metastasis on pretreatment PSMA PET/CT. The median number of cycles received was 3 (range, 1-6) for patients with liver metastasis and 5 (range, 1-6) for those without hepatic involvement. The 50% or greater reduction in PSA from baseline response rate was lower for those with liver metastasis than for those without (30.23% [13/43] vs 49.77% [106/213], P = 0.019). At a median follow-up of 10 mo (interquartile range, 9-13 mo), there was a significant difference in median OS (8.35 mo vs. not reached, P < 0.001). On multivariate analysis, the presence of liver metastasis was independently associated with shorter survival (hazard ratio, 4.06; P < 0.001). Conclusion: Our data suggest that the presence of liver metastasis predicts poorer outcomes in patients receiving LuPSMA treatment. Alternative and combination approaches should be explored to maximize the antitumor activity of radiopharmaceutical therapy in the liver.

Multiparametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT are complementary imaging modalities used in the presurgical evaluation of patients with prostate cancer (PCa). The purpose of this study was to characterize clinically significant PCa (csPCa) detected and not detected by PSMA PET/CT and mpMRI, focusing on tumors detected solely by PSMA PET/CT and overlooked by mpMRI. Methods: We conducted a single-center, retrospective analysis of patients who underwent both PSMA PET/CT and mpMRI within 3 mo of each other and before radical prostatectomy. Two nuclear medicine physicians and 2 radiologists, in a masked manner, independently contoured PCa lesions on PSMA PET/CT and mpMRI, respectively. A consensus read was done with a third reader for each modality, and a majority rule was applied (2:1). After centralized imaging, a pathologic review was done by a genitourinary pathologist. We assessed agreement between imaging modalities and correlation with pathology. Logistic regression models explored associations between clinicopathologic variables and tumor detection on imaging. Results: In total, 132 csPCa tumors from 100 patients were identified on surgical pathology. PSMA PET/CT showed higher lesion-level (87% vs. 80%) and patient-level (98% vs. 94%) sensitivity than mpMRI. Tumors detected on both imaging modalities were larger and had higher grade groups than those not detected by one or both imaging modalities. On multivariable analysis, csPCa tumors undetected by mpMRI but detected by PSMA PET/CT were smaller than those detected by both modalities. Most tumors showing aggressive pathologic features, such as the large cribriform pattern (94.7%) and the intraductal carcinoma (96%), were correctly detected by both imaging modalities. Limitations included selection bias in a surgical cohort. Conclusion: PSMA PET/CT tends to detect smaller csPCa not detected by mpMRI. Larger tumors on pathology with higher grade groups are more likely to be correctly detected by both imaging modalities. These findings provide insights for refining presurgical evaluation strategies in PCa.

This study aimed to investigate the diagnostic efficacy of [⁶⁸Ga]Ga-NYM046 PET/CT in animal models and patients with clear cell renal cell carcinoma (ccRCC) and to compare its performance with that of ¹⁸F-FDG PET/CT. Methods: The in vivo biodistribution of [⁶⁸Ga]Ga-NYM046 was evaluated in mice bearing OS-RC-2 xenografts. Twelve patients with ccRCC were included in the study; all completed paired [⁶⁸Ga]Ga-NYM046 PET/CT and ¹⁸F-FDG PET/CT. The diagnostic efficacies of these 2 PET tracers were compared. Moreover, the positive rate of carbonic anhydrase IX in the pathologic tissue sections was compared with the SUV_max obtained by PET/CT. Results: The tumor accumulation of [⁶⁸Ga]Ga-NYM046 at 1 h after injection in OS-RC-2 xenograft tumor models was 7.21 ± 2.39 injected dose per gram of tissue. Apart from tumors, the kidney and stomach showed high-uptake distributions. In total, 9 primary tumors, 96 involved lymph nodes, and 147 distant metastases in 12 patients were evaluated using [⁶⁸Ga]Ga-NYM046 and ¹⁸F-FDG PET/CT. Compared with ¹⁸F-FDG PET/CT, [⁶⁸Ga]Ga-NYM046 PET/CT detected more primary tumors (9 vs. 1), involved lymph nodes (95 vs. 92), and distant metastases (137 vs. 127). In quantitative analysis, the primary tumors' SUV_max (median, 13.5 vs. 2.4; z = -2.668, P = 0.008) was significantly higher in [⁶⁸Ga]Ga-NYM046 PET/CT. Conversely, the involved lymph nodes' SUV_max (median, 5.9 vs. 7.6; z = -3.236, P = 0.001) was higher in ¹⁸F-FDG PET/CT. No significant differences were found for distant metastases (median SUV_max, 5.0 vs. 5.0; z = -0.381, P = 0.703). Higher [⁶⁸Ga]Ga-NYM046 uptake in primary tumors corresponded to higher expression of carbonic anhydrase IX, with an R ² value of 0.8274. Conclusion: [⁶⁸Ga]Ga-NYM046 PET/CT offers a viable strategy for detecting primary tumors, involved lymph nodes, and distant metastases in patients with ccRCC.

Our rationale was to investigate whether ¹⁸F-FDG PET/MRI in addition to (guideline-recommended) conventional staging leads to changes in therapeutic management in patients with newly diagnosed breast cancer and compare the diagnostic accuracy of ¹⁸F-FDG PET/MRI with that of conventional staging for determining the Union for International Cancer Control (UICC) stage. Methods: In this prospective, double-center study, 208 women with newly diagnosed, therapy-naïve invasive breast cancer were enrolled in accordance with the inclusion criteria. All patients underwent guideline-recommended conventional staging and whole-body ¹⁸F-FDG PET/MRI with a dedicated breast examination. A multidisciplinary tumor board served to determine 2 different therapy recommendations for each patient, one based on conventional staging alone and another based on combined assessment of conventional staging and ¹⁸F-FDG PET/MRI examinations. Major changes in therapy recommendations and differences between the conventional staging algorithm and ¹⁸F-FDG PET/MRI for determining the correct UICC stage were reported and evaluated. Results: Major changes in therapeutic management based on combined assessment of conventional staging and ¹⁸F-FDG PET/MRI were detected in 5 of 208 patients, amounting to changes in therapeutic management in 2.4% (95% CI, 0.78%-5.2%) of the study population. In determining the UICC stage, the guideline-based staging algorithm and ¹⁸F-FDG PET/MRI were concordant in 135 of 208 (64.9%; 95% CI, 58%-71.4%) patients. The conventional guideline algorithm correctly determined the UICC stage in 130 of 208 (62.5%; 95% CI, 55.5%-69.1%) patients, and ¹⁸F-FDG PET/MRI correctly determined the UICC stage in 170 of 208 (81.9%; 95% CI, 75.8%-86.7%) patients. Conclusion: Despite the diagnostic superiority of ¹⁸F-FDG PET/MRI over conventional staging in determining the correct UICC stage, the current (guideline-recommended) conventional staging algorithm is sufficient for adequate therapeutic management of patients with newly diagnosed breast cancer, and ¹⁸F-FDG PET/MRI does not have an impact on patient management.

[¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA) is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC). [¹⁷⁷Lu]Lu-PSMA SPECT/CT 24 h after injection has shown potential as a response biomarker for [¹⁷⁷Lu]Lu-PSMA therapy but is not convenient for patients. This study investigated 4-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT as an alternative to 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT for evaluation of treatment response. Methods: This prospective analysis enrolled 23 patients diagnosed with mCRPC commencing [¹⁷⁷Lu]Lu-PSMA-I&T therapy. Two patients were excluded because of incomplete imaging data. Posttherapy SPECT/CT was performed at 4 and 24 h after the first dose and 4 h after the second dose. Baseline [⁶⁸Ga]Ga-PSMA-11 PET/CT and 4- and 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT were analyzed both visually and semiquantitatively. Bland-Altman plots assessed agreement of semiquantitative parameters from the 4- and 24-h scans. Quantitative assessment of the change in the total tumor volume (TTV) on the 4-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT after the first and second doses was correlated to patient outcomes. Results: All patients had mCRPC previously treated with an androgen receptor pathway inhibitor, and 11 (52%) received prior taxane chemotherapy. Median age was 78 y, and median prostate-specific antigen level was 54 ng/mL. On visual analysis, disease distribution was unchanged among the 3 imaging methods. Eleven patients (52%) had a median of 1 lesion not identified on 4-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT compared with 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT. All missed lesions on the 4-h [¹⁷⁷Lu]Lu SPECT/CT were smaller than 2 cm. Mean differences and agreement between 4- and 24-h SPECT/CT quantitative parameters were within acceptable bounds for lesion number, SUV_max, and SUV_mean, with higher variation observed for TTV. The change in TTV between dose 1 and 2 [¹⁷⁷Lu]Lu-PSMA SPECT/CT predicted prostate-specific antigen progression-free survival. Conclusion: [¹⁷⁷Lu]Lu-PSMA SPECT/CT at 4 h after injection appears a promising alternative to 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT for treatment response assessment, with improved patient convenience.