Journal of Nuclear Medicine最新文献

Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and Arg-Gly-Asp (RGD) peptides have been extensively investigated for imaging of FAP- and integrin α_vβ₃-positive tumors. In this study, a FAPI-RGD heterodimer was radiolabeled with ⁶⁸Ga and evaluated in patients with cancer. We hypothesized that the heterodimer, recognizing both FAP and integrin α_vβ₃, would be advantageous because of its dual-receptor-targeting property. Methods: The effective dose of ⁶⁸Ga-FAPI-RGD was evaluated in 3 healthy volunteers. The clinical feasibility of ⁶⁸Ga-FAPI-RGD PET/CT was evaluated in 22 patients with various types of cancer, and the results were compared with those of ¹⁸F-FDG and ⁶⁸Ga-FAPI-46. Results: ⁶⁸Ga-FAPI-RGD was tolerated well, with no adverse events in any of the healthy volunteers or patients. The effective dose from ⁶⁸Ga-FAPI-RGD PET/CT was 1.01 × 10^-2 mSv/MBq. In clinical investigations with different types of cancer, the radiotracer uptake and tumor-to-background ratio (TBR) of primary and metastatic lesions in ⁶⁸Ga-FAPI-RGD PET/CT were significantly higher than those in ¹⁸F-FDG PET/CT (primary tumors: SUV_max, 18.0 vs. 9.1 [P < 0.001], and TBR, 15.2 vs. 5.5 [P < 0.001]; lymph node metastases: SUV_max, 12.1 vs. 6.1 [P < 0.001], and TBR, 13.3 vs. 4.1 [P < 0.001]), resulting in an improved lesion detection rate and tumor delineation, particularly for the diagnosis of lymph node (99% vs. 91%) and bone (100% vs. 80%) metastases. ⁶⁸Ga-FAPI-RGD PET/CT also yielded a higher radiotracer uptake and TBR than ⁶⁸Ga-FAPI-46 PET/CT did. Conclusion: ⁶⁸Ga-FAPI-RGD exhibited improved tumor uptake and TBR compared with ¹⁸F-FDG and ⁶⁸Ga-FAPI PET/CT. This study demonstrated the safety and clinical feasibility of ⁶⁸Ga-FAPI-RGD PET/CT for imaging of various types of cancer.

System [Formula: see text] is an appealing biomarker for targeting oxidative stress with oncologic PET imaging and can serve as an alternative PET biomarker to other metabolic indicators. In this paper, we report a direct comparison of 2 ¹⁸F-labeled amino acid radiopharmaceuticals targeting system [Formula: see text], [¹⁸F]5-fluoroaminosuberic acid ([¹⁸F]FASu) and (4S)-4-(3-[¹⁸F]fluoropropyl)-l-glutamate ([¹⁸F]FSPG), in terms of their uptake specificity and ability to image glioma and lung cancer xenografts in vivo. Methods: Both tracers were synthesized according to previously published procedures. In vitro uptake specificity assays were conducted using prostate (PC-3), glioblastoma (U-87), colorectal (HT-29), ovarian (SKOV3), breast (MDA-MB-231), and lung cancer (A549) cell lines. PET/CT imaging and biodistribution studies were conducted in immunocompromised mice bearing U-87 or A549 xenografts. Results: In vitro cell uptake assays showed that the tracers accumulated in cancer cells in a time-dependent manner and that the uptake of [¹⁸F]FASu was blocked by the system [Formula: see text] inhibitor sulfasalazine and rose bengal, but not by system L inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, system [Formula: see text] inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid, or l-serine, which is a substrate for transporter systems A, ACS, B⁰, and B^0,+ Conversely, [¹⁸F]FSPG uptake decreased significantly in the presence of an excess of L-trans-pyrrolidine-2,4-dicarboxylic acid in 2 of 3 tested cell lines, indicating some reliance on system [Formula: see text] in these cells. In an in vivo setting, [¹⁸F]FASu and [¹⁸F]FSPG generated good-contrast PET images in U-87 and A549 tumor-bearing mice. Tracer accumulation in A549 tumors was 5.0 ± 0.8 percentage injected dose (%ID)/g ([¹⁸F]FASu, n ≥ 5) and 6.3 ± 1.3 %ID/g ([¹⁸F]FSPG, n ≥ 6, P = 0.7786), whereas U-87 xenografts demonstrated uptake of 6.1 ± 2.4 %ID/g ([¹⁸F]FASu, n ≥ 4) and 11.2 ± 4.1 %ID/g ([¹⁸F]FSPG, n ≥ 4, P = 0.0321) at 1 h after injection. Conclusion: [¹⁸F]FSPG had greater in vitro uptake than [¹⁸F]FASu in all cell lines tested; however, our results indicate that residual uptake differences exist between [¹⁸F]FSPG and [¹⁸F]FASu, suggesting alternative transporter activity in the cell lines tested. In vivo studies demonstrated the ability of both [¹⁸F]FASu and [¹⁸F]FSPG to image glioblastoma (U-87) and non-small cell lung cancer (A549) xenografts.

Fibroblast-activation protein is a promising target for oncologic molecular imaging. Studies show that fibroblast activation protein inhibitor (FAPI) radiotracers are accurate diagnostics with favorable tumor-to-background ratios across various cancers. Therefore, we performed a systematic review and metaanalysis to assess the diagnostic performance of FAPI PET/CT in comparison with [¹⁸F]FDG PET/CT, the most widely used radiotracer in oncology. Methods: We conducted a systematic search in MEDLINE, Embase, Scopus, PubMed, Cochrane Central Register of Controlled Trials, relevant trial registries, and bibliographies. The search consisted of combinations of terms for 3 topics: neoplasia, PET/CT, and FAPI. Two authors independently screened retrieved articles using predefined inclusion and exclusion criteria and extracted the data. Study quality was assessed using the criteria of QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). For each study, the sensitivity, specificity, and 95% CIs were calculated to determine diagnostic accuracy for primary, nodal, and metastatic lesions. A random-effects metaanalysis was used for pooling the data, and heterogeneity was assessed (I² index). Results: Thirty-nine studies (1,259 patients) investigating the use of FAPI PET/CT were included. On a patient-based analysis, pooled sensitivity was 0.99 (95% CI, 0.97-1.0) for the detection of primary lesions. Pooled sensitivity for nodal and distant metastases was 0.91 (95% CI, 0.81-0.96) and 0.99 (95% CI, 0.96-1.0), respectively. On a paired analysis between FAPI and [¹⁸F]FDG PET/CT, FAPI had a higher sensitivity in the detection of primary, nodal, and metastatic lesions (all P < 0.001). The differences in sensitivities between FAPI and [¹⁸F]FDG were statistically significant. In terms of heterogeneity, analyses on primary lesions were moderately affected, distant metastatic lesions were highly affected, and the nodal metastatic analyses had negligible heterogeneity. Conclusion: The diagnostic performance of FAPI PET/CT is superior to that of [¹⁸F]FDG in the detection of primary, nodal, and distant metastases. However, further studies are needed to better evaluate its utility and indication in specific cancer types and clinical settings.

Total-body PET/CT images can be rendered to produce images of a subject's face and body. In response to privacy and identifiability concerns when sharing data, we have developed and validated a workflow that obscures (defaces) a subject's face in 3-dimensional volumetric data. Methods: To validate our method, we measured facial identifiability before and after defacing images from 30 healthy subjects who were imaged with both [¹⁸F]FDG PET and CT at either 3 or 6 time points. Briefly, facial embeddings were calculated using Google's FaceNet, and an analysis of clustering was used to estimate identifiability. Results: Faces rendered from CT images were correctly matched to CT scans at other time points at a rate of 93%, which decreased to 6% after defacing. Faces rendered from PET images were correctly matched to PET images at other time points at a maximum rate of 64% and to CT images at a maximum rate of 50%, both of which decreased to 7% after defacing. We further demonstrated that defaced CT images can be used for attenuation correction during PET reconstruction, introducing a maximum bias of -3.3% in regions of the cerebral cortex nearest the face. Conclusion: We believe that the proposed method provides a baseline of anonymity and discretion when sharing image data online or between institutions and will help to facilitate collaboration and future regulatory compliance.

Radioligand therapy (RLT) with ¹⁷⁷Lu-prostate-specific membrane antigen (PSMA) inhibitors ([¹⁷⁷Lu]Lu-PSMA) is currently approved for patients with metastatic castration-resistant prostate cancer (mCRPC) after progression with at least 1 taxane and 1 androgen-receptor-pathway inhibitor. However, the impact of prior chemotherapy on [¹⁷⁷Lu]Lu-PSMA-RLT outcomes is debatable, with various studies showing inconsistent results. This study was conducted to precisely evaluate the impact of prior taxane chemotherapy on response and survival outcomes in mCRPC patients after [¹⁷⁷Lu]Lu-PSMA-RLT. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches in PubMed, Scopus, and Embase were made using relevant key words, and articles up to December 2022 were included. The endpoints included prostate-specific antigen (PSA) response rate (RR), progression-free survival, and overall survival (OS). Individual patient data were pooled when feasible. Univariate odds ratios (ORs) and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates and 95% CIs were generated using metaanalysis. Results: Thirteen articles comprising 2,068 patients were included. In 6 articles (553 patients), taxane-naïve patients had significantly better odds of biochemical response after [¹⁷⁷Lu]Lu-PSMA-RLT (pooled OR, 1.82; 95% CI, 1.21-2.71). Individual patient data metaanalysis for PSA RRs in 3 articles revealed a significantly higher PSA RR in the taxane-naïve versus taxane-treated patients (57.1% vs. 39.5%; difference, 17.6%; 95% CI, 5.6%-28.9%). Further, taxane-naïve status was also a predictor of significantly better progression-free survival (5 articles; 1,027 patients; pooled HR, 0.60; 95% CI, 0.51-0.69) and OS (8 articles; 1,594 patients; pooled HR, 0.54; 95% CI, 0.43-0.68) after [¹⁷⁷Lu]Lu-PSMA-RLT. There was no evidence of publication bias. Conclusion: mCRPC patients with no prior taxanes had significantly better outcomes after [¹⁷⁷Lu]Lu-PSMA-RLT than did taxane-treated patients. Further trials evaluating [¹⁷⁷Lu]Lu-PSMA-RLT in the taxane-naïve setting are now required.

[ ⁶⁸Ga]Ga-PSMA-11 ( ⁶⁸Ga-PSMA-11) is used to identify prostate-specific membrane antigen (PSMA)-positive tumors on PET scans. In the VISION study, ⁶⁸Ga-PSMA-11 was used to determine the eligibility of patients with metastatic castration-resistant prostate cancer for treatment with [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617), based on predefined read criteria. This substudy aimed to investigate the interreader variability and intrareader reproducibility of visual assessments of ⁶⁸Ga-PSMA-11 PET/CT scans using the VISION read criteria and evaluate the agreement between read results for this and the VISION study. Methods: In VISION, ⁶⁸Ga-PSMA-11 PET/CT scans were centrally read as inclusion cases if they had at least 1 PSMA-positive lesion and no PSMA-negative lesions that fulfilled the exclusion criteria. In this substudy, 125 PET/CT scans (75 inclusion and 50 exclusion cases) were randomly selected from VISION and retrospectively assessed by 3 independent central readers. A random subset of 20 cases (12 inclusion and 8 exclusion cases) was recoded for assessment of intrareader reproducibility. Classification of cases as inclusion or exclusion cases was based on the VISION read criteria. Overall interreader variability was assessed by Fleiss κ-statistics, and pairwise variability and intrareader reproducibility were assessed by Cohen κ-statistics. Results: For interreader variability, the readers agreed on 77% of cases (overall average agreement rate, 0.85; Fleiss κ, 0.60 [95% CI, 0.50-0.70]). The pairwise agreement rate was 0.82, 0.88, and 0.84, and the corresponding Cohen κ was 0.54 (95% CI, 0.38-0.71), 0.67 (95% CI, 0.52-0.83), and 0.59 (95% CI, 0.43-0.75), respectively. For intrareader reproducibility, the agreement rate was 0.90, 0.90, and 0.95, and the corresponding Cohen κ was 0.78 (95% CI, 0.49-0.99), 0.76 (95% CI, 0.46-0.99), and 0.89 (95% CI, 0.67-0.99), respectively. The number of actual VISION inclusion cases out of the total number of cases scored as inclusion in this substudy was 71 of 93 (agreement rate, 0.76; 95% CI, 0.66-0.85) for reader 1, 70 of 88 (0.80; 0.70-0.87) for reader 2, and 73 of 96 (0.76; 0.66-0.84) for reader 3. All readers agreed on 66 of 75 VISION inclusion cases. Conclusion: Moderate-to-substantial interreader agreement and substantial-to-almost perfect intrareader reproducibility for ⁶⁸Ga-PSMA-11 PET/CT scan assessment using the VISION read criteria were observed. The read rules applied in VISION can be readily learned and demonstrate good reproducibility.

Cancer of unknown primary (CUP) is a heterogeneous entity with a limited prognosis. Novel prognostic markers are needed for patient stratification in prospective clinical trials exploring innovative therapies. Methods: In CUP patients treated at the West German Cancer Center Essen, the prognostic value of ¹⁸F-FDG PET/CT at the initial diagnostic workup was analyzed by comparing overall survival (OS) in patients who underwent ¹⁸F-FDG PET/CT with those who did not. Results: Of 154 patients with a CUP diagnosis, 76 underwent ¹⁸F-FDG PET/CT at the initial diagnostic workup. The median overall survival (OS) of the full analysis set was 20.0 mo. Within the PET/CT subgroup, an SUV_max above 20 was associated with significantly superior OS (median OS, not reached vs. 32.0 mo; hazard ratio, 0.261; 95% CI, 0.095-0.713; P = 0.009). Conclusion: Our retrospective work shows that an SUV_max above 20 on ¹⁸F-FDG PET/CT at the initial diagnostic workup is a favorable prognostic factor in patients with CUP. This finding deserves further prospective studies for validation.

The worldwide proliferation of persistent environmental pollutants is accelerating at an alarming rate. Not surprisingly, many of these pollutants pose a risk to human health. In this review, we examine recent literature in which molecular imaging and radiochemistry have been harnessed to study environmental pollutants. Specifically, these techniques offer unique ways to interrogate the pharmacokinetic profiles and bioaccumulation patterns of pollutants at environmentally relevant concentrations, thereby helping to determine their potential health risks.