[68Ga]Pentixafor PET/CT for staging and prognostic assessment of newly diagnosed multiple myeloma: comparison to [18F]FDG PET/CT.

PURPOSE: To evaluate the prognostic performance of [68Ga]Pentixafor PET/CT at baseline for staging of patients with newly diagnosed multiple myeloma (MM) and to compare it with [18F]FDG PET/CT and the Revised-International Staging System (R-ISS). METHODS: Patients who underwent [68Ga]Pentixafor and [18F]FDG PET/CT imaging were retrospectively included. Patient staging was performed according to the Durie-Salmon PLUS staging system based on [68Ga]Pentixafor PET/CT and [18F]FDG PET/CT images, and the R-ISS. Progression-free survival (PFS) at patient follow-up was estimated using the Kaplan-Meier estimator and compared using the log-rank test. Area under the receiver operating characteristic curve (AUC) was calculated to assess predictive performance. RESULTS: Fifty-five MM patients were evaluated. Compared with [18F]FDG PET, [68Ga]Pentixafor PET detected 25 patients as the same stage, while 26 patients were upstaged and 4 patients were downstaged (P = 0.001). After considering the low-dose CT data, there was no statistically significant difference in the number of patients classified in each stage using [68Ga]Pentixafor PET/CT and [18F]FDG PET/CT (P = 0.091). [68Ga]Pentixafor PET/CT-based staging discriminated PFS outcomes in patients with different disease stages (stage I vs. stage II, stage I vs. stage III, and stage II vs. stage III; all P < 0.05), whereas for [18F]FDG PET/CT, there was only a difference in median PFS between stage I and III (P = 0.021). When staged by R-ISS, the median PFS for stage III was significantly lower than that for stage I and II (P = 0.008 and 0.035, respectively). When predicting 2-year PFS based on staging, the AUC of [68Ga]Pentixafor PET/CT was significantly higher than that of [68Ga]Pentixafor PET (0.923 vs. 0.821, P = 0.002), [18F]FDG PET (0.923 vs. 0.752 P = 0.002), and R-ISS (0.923 vs. 0.776, P = 0.005). CONCLUSIONS: [68Ga]Pentixafor PET/CT-based staging possesses substantial potential to predict disease progression in newly diagnosed MM patients.

A head-to-head comparison of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in patients with nasopharyngeal carcinoma: a single-center, prospective study.

PURPOSE: We aimed to compare the staging efficiency of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in nasopharyngeal carcinoma (NPC) patients. METHODS: Thirty-nine patients with pathologically confirmed NPC were enrolled in this prospective study. Each patient underwent paired [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT on 2 successive days. The accuracy of two PET/CT for assessing T, N, and M stages was compared by using head-and-neck MRI, histopathologic diagnosis and follow-up results as reference standards. The radiotracer uptake derived from two PETs was also compared. RESULTS: For treatment-naïve patients, [68Ga]Ga-DOTATATE PET/CT showed identical sensitivity for the primary tumours but clearer tumor delineation induced by higher tumour-to-background (TBR) ratio (19.1 ± 8.7 vs. 12.4 ± 7.7, P = 0.003), compared with [68Ga]Ga-FAPI PET/CT. Regarding cervical lymph node (CLN) metastases, [68Ga]Ga-DOTATATE PET had significantly better sensitivity and accuracy based on neck sides (98% vs. 82%, P < 0.001; 99% vs. 88% P = 0.008), neck levels (98% vs. 78%, 99% vs. 97%; both P < 0.001) and individual nodes (89% vs. 56%, 91% vs. 76%; both P < 0.001), and higher TBR (8.1 ± 4.1 vs. 6.3 ± 3.7, P < 0.001). Additionally, [68Ga]Ga-DOTATATE PET/CT revealed higher sensitivity and accuracy for distant metastases (96% vs. 53%, 95% vs. 52%; both P < 0.001), particularly in bone metastases (99% vs. 49%, 97% vs. 49%; both P < 0.001). For post-treatment patients, [68Ga]Ga-DOTATATE PET/CT identified one more true-negative case than [68Ga]Ga-FAPI PET/CT. CONCLUSION: [68Ga]Ga-DOTATATE PET/CT performed better than [68Ga]Ga-FAPI PET/CT in visualizing the primary tumours, detecting the metastatic lesions and identifying the local recurrence, suggesting [68Ga]Ga-DOTATATE PET/CT may be superior to [68Ga]Ga-FAPI PET/CT for NPC staging.

A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [177Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer.

PURPOSE: This translational study aimed to determine the maximum tolerated dose (MTD), safety, dosimetry, and therapeutic efficacy of 177Lu-PSMA-EB-01 (denoted as [177Lu]Lu-LNC1003) in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A total of 13 patients with mCRPC were recruited in this study. A standard 3 + 3 dose escalation protocol was performed. The following dose levels were ultimately evaluated: 1.11, 1.85, and 2.59 GBq/cycle. Patients received [177Lu]Lu-LNC1003 therapy for up to two cycles at a 6-week interval. RESULTS: Patients received fractionated doses of [177Lu]Lu-LNC1003 ranging from 1.11 to 2.59 GBq per cycle. Myelosuppression was dose-limiting at 2.59 GBq, and 1.85 GBq was determined to be the MTD. The total-body effective dose for 177Lu-LNC1003 was 0.35 ± 0.05 mSv/MBq. The salivary glands were found to receive the highest estimated radiation dose, which was calculated to be 3.61 ± 2.83 mSv/MBq. The effective doses of kidneys and red bone marrow were 1.88 ± 0.35 and 0.22 ± 0.04 mSv/MBq, respectively. The tumor mean absorbed doses for bone and lymph node metastases were 8.52 and 9.51 mSv/MBq. Following the first treatment cycle, PSA decline was observed in 1 (33.3%), 4 (66.7%), and 2 (50.0%) patients at dose levels 1 (1.11 GBq), 2 (1.85 GBq), and 3 (2.59 GBq), respectively. Compared with the baseline serum PSA value, 1 (33.3%) at dose level 1 and 4 (66.6%) patients at dose level 2, presented a PSA decline after the second treatment cycle. CONCLUSION: This phase 1 trial revealed that the MTD of [177Lu]Lu-LNC1003 is 1.85 GBq. The treatment with multiple cycles at the dose of 1.11 GBq /cycle and 1.85 GBq /cycle was well tolerated. [177Lu]Lu-LNC1003 has higher tumor effective doses in bone and lymph nodes metastases while the absorbed dose in the red bone marrow should be closely monitored in future treatment studies with higher doses and multiple cycles. The frequency of administration also needs to be further explored to assess the efficacy and side effects of [177Lu]Lu-LNC1003 treatment. TRIAL REGISTRATION: 177Lu-PSMA-EB-01 in patients with metastatic castration-resistant prostate cancer (NCT05613738, Registered 14 November 2022). URL of registry https://classic. CLINICALTRIALS: gov/ct2/show/NCT05613738.

[68Ga]Ga­LNC1007 PET/CT in the evaluation of renal cell carcinoma: comparison with 2-[18F]FDG/[68Ga]Ga-PSMA PET/CT.

PURPOSE: To compare the potential efficiency of [68Ga]Ga-LNC1007 with 2-[18F]FDG/[68Ga]Ga-PSMA PET/CT for detecting renal cell carcinoma (RCC) and to explore parameters derived from [68Ga]Ga-LNC1007 PET/CT for discriminating pathological characteristics in RCC. METHODS: Twenty-five RCC patients confirmed by pathology were enrolled in this prospective study. The maximum standardized uptake value (SUVmax), mean SUV (SUVmean), gross tumor volume (GTV) and total lesion-tracer (TL-tracer) of lesions were calculated from the corresponding PET/CT images. Pathological characteristics included World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and adverse pathological features (tumor necrosis or sarcomatoid or rhabdoid feature). RESULTS: [68Ga]Ga-LNC1007 PET/CT showed a higher detection rate for primary lesions than 2-[18F]FDG and [68Ga]Ga-PSMA (LNC1007 vs. FDG: 13/17 vs. 4/17, P = 0.005; LNC1007 vs. PSMA: 9/11 vs. 6/11, P = 0.361). [68Ga]Ga-LNC1007 PET/CT showed higher SUVmax (6.6 vs. 3.7, P = 0.005), SUVmean (4.1 vs. 2.3, P = 0.001) and TBR (2.6 vs. 1.7, P = 0.011) compared with 2-[18F]FDG PET/CT, and it also showed higher TBR (2.9 vs. 0.5, P = 0.003), TBR-delay (2.8 vs. 0.3, P = 0.003), GTV (84.1 vs. 42.9, P = 0.003) and TL-tracer (442.7 vs. 235.8, P = 0.008) compared with [68Ga]Ga-PSMA PET/CT. SUVmax and TBR derived from [68Ga]Ga-LNC1007 PET/CT could effectively differentiate WHO/ISUP grade (3-4 vs. 1-2) and adverse pathological features (positive vs. negative) (SUVmax: AUC 0.81, P = 0.04; AUC 0.80, P = 0.033; TBR: AUC 0.84, P = 0.026; AUC 0.85, P = 0.014). The SUVmax was positively correlated with the FAP expression, integrin αvß3 expression and the total expression of FAP and integrin αvß3 (r = 0.577, P = 0.006, r = 0.701, P < 0.001, and r = 0.702, P < 0.001, respectively). CONCLUSION: [68Ga]Ga-LNC1007 is a promising tracer for RCC imaging and can effectively identify aggressive pathological characteristics of RCC.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study.

OBJECTIVES: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. MATERIALS AND METHODS: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. RESULTS: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. CONCLUSIONS: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Fibroblast Activation Protein-α Responsive Peptide Assembling Prodrug Nanoparticles for Remodeling the Immunosuppressive Microenvironment and Boosting Cancer Immunotherapy.

Checkpoint blockade immunotherapy has broad application prospects in the clinical treatment of malignant tumors. However, the low response rate of the checkpoint blockade is due to low tumor immunogenicity and immunosuppression within the tumor microenvironment. Herein, the authors design an amphiphilic bifunctional PD-1/PD-L1 peptide antagonist PCP, and co-deliver doxorubicin (DOX) and R848 through co-assembly of a multi-agent prodrug (PCP@R848/DOX), which can be specifically cleaved by fibroblast activation protein-α (FAP-α) in the tumor stroma. Upon reaching the tumor tissue, the PCP@R848/DOX prodrug nanostructure is disassembled by FAP-α. The localized release of DOX and R848 triggers immunogenic cell death (ICD) and reprograms tumor-associated macrophages (TAMs) to elicit antitumor immunity. Furthermore, sustained release of PD-1 or PD-L1 peptide antagonists mediates the PD-L1 pathway blockade for further propagated activation of cytotoxic T lymphocytes. Notably, a tumor microenvironment activatable prodrug nanoparticle is presented for triple-modality cancer therapy that functions by simultaneously activating ICD and altering the phenotype of TAMs when combined with PD-1 blockade therapy, which efficiently elicits a strong systemic antitumor immune response. This strategy may emerge as a new paradigm in the treatment of cancer by combination immunotherapy.

[68Ga]Ga-DOTA-FAPI-04 PET/CT in the evaluation of gastric cancer: comparison with [18F]FDG PET/CT.

PURPOSE: This study aimed to compare the performance of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT in the evaluation of primary and metastatic lesions of gastric cancer. METHODS: Fifty-six patients with histologically proven gastric carcinomas were enrolled in this study, including 45 patients for staging and 11 patients for restaging after surgery. Each patient underwent both [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week. The activity of tracer accumulation in lesions was assessed by maximum standardized uptake value (SUVmax) and TBR (lesions SUVmax/ascending aorta SUVmean). Histological workup served as a standard of reference. If tissue diagnosis was not applicable, the follow-up data including the results of laboratory tests and medical imaging could also serve as a reference. RESULTS: [68Ga]Ga-DOTA-FAPI-04 PET/CT was comparable to [18F]FDG on detecting primary tumors and lymph node (LN) metastases, whereas [68Ga]Ga-DOTA-FAPI-04 outperformed [18F]FDG in detecting peritoneal (159 vs. 47, P < 0.001) and bone metastases (64 vs. 55, P = 0.003) by the lesion-based analysis. [68Ga]Ga-DOTA-FAPI-04 showed higher SUVmax (10.3 vs. 8.1, P = 0.004) and TBR (11.6 vs. 5.8, P < 0.001) in primary tumor, and higher TBR in LN involvement (8.0 vs. 3.7, P < 0.001) and peritoneal metastases (8.1 vs. 3.2, P < 0.001), compared with [18F]FDG PET/CT. The specificity and positive predictive value of [68 Ga]Ga-DOTA-FAPI-04 were significantly higher than that of [18F]FDG (100.0% vs. 97.7%, P < 0.001; 100.0% vs. 57.1%, P = 0.001) in determining the LN status. [68Ga]Ga-DOTA-FAPI-04 was comparable to [18F]FDG in evaluating N-staging (47.1% vs. 23.5%, P = 0.282). [68Ga]Ga-DOTA-FAPI-04 PET/CT detected more positive recurrent lesions in all restaging patients and showed clearer tumor delineation. Two patients underwent follow-up [68Ga]Ga-DOTA-FAPI-04 PET/CT scans after chemotherapy, which both showed remission. CONCLUSIONS: [68Ga]Ga-DOTA-FAPI-04 PET/CT can better evaluate primary gastric cancer and metastatic lesions in the peritoneum, abdominal LNs, and bone. Furthermore, [68Ga]Ga-DOTA-FAPI-04 PET/CT provided more information for patients with recurrent disease and had the potential in monitoring response to treatment.

Accurate preoperative staging with [68Ga]Ga-FAPI PET/CT for patients with oral squamous cell carcinoma: a comparison to 2-[18F]FDG PET/CT.

OBJECTIVE: To evaluate the potential value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in preoperative staging for patients with oral squamous cell carcinoma (OSCC) as compared to 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET/CT. METHODS: Thirty-six treatment-naïve patients with OSCC who underwent 2-[18F]FDG and [68Ga]Ga-FAPI PET/CT for preoperative staging were enrolled. The maximum standardised uptake value (SUVmax) of the primary tumour and suspected cervical metastatic lymph nodes, and the tumour-to-background ratio (TBR) of the primary tumour, were measured. The accuracy of two imaging modalities for preoperative diagnosis of metastatic lymph nodes was analysed. Histopathology served as the standard of reference. RESULTS: Thirty-seven primary lesions of 36 patients were accurately detected by both [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT. Regarding primary tumours, the SUVmax and TBR of the two imaging modalities in stage T3-T4 were significantly higher than those of stage T1-T2 (all p < 0.05). On the patient analysis, the accuracy for the evaluation of N1-N3 neck status was 52.6% (10/19) for [68Ga]Ga-FAPI PET/CT and 57.9% (11/19) for 2-[18F]FDG PET/CT. Notably, the accuracy for the evaluation of the N0 neck status between [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT was 100% (17/17) and 29% (5/17), respectively. Based on the patient, neck side and neck level, [68Ga]Ga-FAPI PET/CT resulted in higher specificity and accuracy in diagnosing metastatic neck lymph nodes than 2-[18F]FDG PET/CT (all p < 0.05). CONCLUSION: [68Ga]Ga-FAPI PET/CT is a promising tool for preoperative staging of OSCC, and appears to reduce the false positivity seen with 2-[18F]FDG PET/CT for the detection of neck lymph node metastases. KEY POINTS: • [68Ga]Ga-FAPI PET/CT is a promising tool targeting cancer-associated fibroblasts with comparable diagnostic performance to 2-[18F]FDG PET/CT for identifying the primary lesions of OSCC. • [68Ga]Ga-FAPI PET/CT showed higher specificity and accuracy for the evaluation of neck lymph node metastases of OSCC than 2-[18F]FDG PET/CT, especially for N0 neck status.

Non-invasive assessment of heterogeneity of gliomas using diffusion and perfusion MRI: correlation with spatially co-registered PET.

BACKGROUND: Heterogeneity of gliomas challenges the neuronavigated biopsy and oncological therapy. Diffusion and perfusion magnetic resonance imaging (MRI) can reveal the cellular and hemodynamic heterogeneity of tumors. Integrated positron emission tomography (PET)/MRI is expected to be a non-invasive imaging approach to characterizing glioma. PURPOSE: To evaluate the value of apparent diffusion coefficient (ADC), cerebral blood volume (CBV), and spatially co-registered maximal standard uptake value (SUVmax) for tissue characterization and glioma grading. MATERIAL AND METHODS: Thirty-seven consecutive patients with pathologically confirmed gliomas were retrospectively investigated. The relative minimum ADC (rADCmin), relative maximal ADC (rADCmax), relative maximal rCBV (rCBVmax), the relative minimum rCBV (rCBVmin), and the corresponding relative SUVmax (rSUVmax) were measured. The paired t-test was used to compare the quantitative parameters between different regions to clarify tumor heterogeneity. Imaging parameters between WHO grade IV and grade II/III gliomas were compared by t-test. The diagnostic efficiency of multiparametric PET/MRI was analyzed by receiver operating characteristic (ROC) curve. RESULTS: The values of rSUVmax were significantly different between maximal diffusion/perfusion area and minimum diffusion/perfusion area (P < 0.001/P < 0.001) within tumor. The values of rADCmin (P < 0.001), rCBVmax (P = 0.002), and corresponding rSUVmax (P = 0.001/P < 0.001) could be used for grading gliomas. The areas under the ROC curves of rSUVmax defined by rADCmin and rCBVmax were 0.89 and 0.91, respectively. CONCLUSION: Diffusion and perfusion MRI can detect glioma heterogeneity with excellent molecular imaging correlations. Regions with rCBVmax suggest tissues with the highest metabolism and malignancy for guiding glioma grading and tissue sampling.

A novel deep-learning-based approach for automatic reorientation of 3D cardiac SPECT images.

PURPOSE: Reconstructed transaxial cardiac SPECT images need to be reoriented into standard short-axis slices for subsequent accurate processing and analysis. We proposed a novel deep-learning-based method for fully automatic reorientation of cardiac SPECT images and evaluated its performance on data from two clinical centers. METHODS: We used a convolutional neural network to predict the 6 rigid-body transformation parameters and a spatial transformation network was then implemented to apply these parameters on the input images for image reorientation. A novel compound loss function which balanced the parametric similarity and penalized discrepancy of the prediction and training dataset was utilized in the training stage. Data from a set of 322 patients underwent data augmentation to 6440 groups of images for the network training, and a dataset of 52 patients from the same center and 23 patients from another center were used for evaluation. Similarity of the 6 parameters was analyzed between the proposed and the manual methods. Polar maps were generated from the output images and the averaged count values of the 17 segments were computed from polar maps to evaluate the quantitative accuracy of the proposed method. RESULTS: All the testing patients achieved automatic reorientation successfully. Linear regression results showed the 6 predicted rigid parameters and the average count value of the 17 segments having good agreement with the reference manual method. No significant difference by paired t-test was noticed between the rigid parameters of our method and the manual method (p > 0.05). Average count values of the 17 segments show a smaller difference of the proposed and manual methods than those between the existing and manual methods. CONCLUSION: The results strongly indicate the feasibility of our method in accurate automatic cardiac SPECT reorientation. This deep-learning-based reorientation method has great promise for clinical application and warrants further investigation.

Imaging and monitoring HER2 expression in breast cancer during trastuzumab therapy with a peptide probe 99mTc-HYNIC-H10F.

PURPOSE: The novel molecular imaging probe 99mTc-HYNIC-H10F was developed for patient screening and efficacy monitoring of trastuzumab therapy by SPECT imaging of HER2 expression in breast cancer. METHODS: 99mTc-HYNIC-H10F was developed by labeling H10F peptide with 99mTc following an optimized protocol. Biodistribution and SPECT/CT were performed in mouse models bearing HER2-positive SK-BR3 and HER2-negative MDA-MB-231 human breast cancer xenografts, respectively. The treatment response to trastuzumab was monitored and quantified by SPECT/CT in two HER2-positive breast cancer models (SK-BR3 and MDA-MB-361). The preliminary clinical study was performed in two patients with breast cancer. RESULTS: SPECT/CT with 99mTc-HYNIC-H10F showed that the SK-BR3 tumors were clearly visualized, while the signals from MDA-MB-231 tumors were much lower. The tumor uptake of 99mTc-HYNIC-H10F could be blocked by excess unlabeled H10F peptide but not by excess trastuzumab. The growth of two HER2-positive tumors was prominently suppressed at day 11 post-treatment. However, SPECT/CT reflected much earlier therapy response at day 4 post-treatment. The HER2 expression in tumors of breast cancer patients could be detected by 99mTc-HYNIC-H10F SPECT/CT imaging. CONCLUSIONS: 99mTc-HYNIC-H10F specifically accumulates in HER2-positive tumors. Compared with trastuzumab, 99mTc-HYNIC-H10F binds to a different domain of HER2 antigen, providing new opportunities to monitor HER2 expression levels before/during/after trastuzumab treatment for more effective personalized treatment.

18F-FDGPET/CT in fever of unknown origin and inflammation of unknown origin: a Chinese multi-center study.

PURPOSE: To evaluate the clinical value of 18F-FDG-PET/CT for the diagnosis of fever of unknown origin (FUO) and inflammation of unknown origin (IUO) in Chinese population, as well as the characteristics of PET/CT in different category of etiological disease. METHODS: A total of 376 consecutive patients with FUO/IUO who underwent FDG-PET/CT at 12 hospitals were retrospectively studied. FDG uptake was quantitatively and visually evaluated, by using SUVmax and a 4-grade scale respectively. A questionnaire survey to the clinicians was used to evaluate the significance of PET/CT in diagnosing of FUO/IUO. Data analysis included the etiological distribution in the study population, image characteristics in different category of diseases, and clinical significance of PET/CT. RESULTS: In 376 studied patients, the infectious diseases accounted for 33.0% of patients, rheumatologic diseases for 32.4%, malignancies for 19.1%, miscellaneous causes for 6.6%, and cause unknown for 8.8%. However, the etiological distribution among hospitals was varied. In addition, the etiological disease composition ratio has changed over time in China. On PET/CT examinations, 358 (95.2%) of the patients had a positive finding. Within them, local high uptake lesion was found in 219 cases, and nonspecific abnormal uptake (NAU) was found in 187 cases. FDG uptake in malignant diseases was significantly higher than in other category diseases both on SUVmax and visual scores (t-value range from 4.098 to 5.612, all P value < 0.001). Based on a clinical questionnaire survey, PET/CT provided additional diagnostic information for 77.4% of patients, and 89.6% of patients benefited from PET/CT examination. CONCLUSIONS: FDG PET/CT is a valuable tool for clinical diagnosis of FUO/IUO, and it is of great significance in further investigating the usefulness of PET/CT in non-neoplastic diseases.

68 Ga-DOTATATE PET/CT Detected Bone Metastasis Earlier Than 68 Ga-FAPI PET/CT and 99m Tc-MDP Bone Scintigraphy in a Patient With Nasopharyngeal Carcinoma.

ABSTRACT: A 53-year-old man with newly diagnosed nasopharyngeal carcinoma (NPC) underwent 99m Tc-MDP bone scintigraphy for the potential bone metastases, and paired 68 Ga-DOTATATE and 68 Ga-FAPI PET/CT for initial staging. 68 Ga-DOTATATE PET/CT identified 2 abnormal foci with increased tracer uptake in the cervical vertebra and the ilium, whereas 68 Ga-FAPI PET/CT and bone scan detected only the ilium lesion. A subsequent biopsy confirmed NPC metastasis in the ilium. Furthermore, baseline and follow-up bone scintigraphy revealed that the positive lesion in the cervical vertebra, as indicated in 68 Ga-DOTATATE PET/CT, was also a bone metastasis. This case highlighted the potential superiority of 68 Ga-DOTATATE in NPC.

68Ga-FAPI-RGD PET/CT Detected Skull Metastasis Better Than 18F-FDG in a Patient With Radioiodine-Refractory Differentiated Thyroid Cancer.

ABSTRACT: A 60-year-old woman underwent resection of a right humeral tumor 1 year ago, and postoperative pathology indicated metastatic papillary thyroid cancer. She had her first 131I treatment after a total thyroidectomy. Subsequent whole-body imaging after 131I administration revealed 131I-avid metastases in the left parietal bone. These metastases were observed to be larger during her second 131I treatment, conducted 6 months later. Consequently, the patient was diagnosed with radioiodine-refractory differentiated thyroid cancer. 68Ga-FAPI-RGD PET/CT demonstrated higher tracer uptake and clearer lesion boundaries compared with 18F-FDG PET/CT. This suggests that 177Lu-FAPI-RGD could potentially serve as a treatment option for radioiodine-refractory differentiated thyroid cancer.

Diagnostic Performance of [18F]AlF-Thretide PET/CT in Patients with Newly Diagnosed Prostate Cancer Using Histopathology as Reference Standard.

This study aimed to assess the diagnostic value of [18F]AlF-thretide PET/CT in patients with newly diagnosed prostate cancer (PCa). Methods: In total, 49 patients with biopsy-proven PCa were enrolled in this prospective study. All patients underwent [18F]AlF-thretide PET/CT, and the scoring system of the PRIMARY trial was used for PET image analysis. The dosimetry evaluation of [18F]AlF-thretide was performed on 3 patients. Pathologic examination was used as the reference standard to evaluate the location, number, size, and Gleason score of tumors, for comparison with the [18F]AlF-thretide PET/CT results. PSMA expression was evaluated by immunohistochemical staining. Results: All patients tolerated the [18F]AlF-thretide PET/CT well. The total effective dose of [18F]AlF-thretide was 1.16E-02 mSv/MBq. For patient-based analysis of intraprostatic tumors, 46 of 49 (93.9%) patients showed pathologic uptake on [18F]AlF-thretide PET/CT. For lesion-based analysis of intraprostatic tumors, the sensitivity and positive predictive value for [18F]AlF-thretide PET/CT were 58.2% and 90.5%, respectively. Delayed images can detect more lesions than standard images (n = 57 vs. 49, P = 0.005), and the SUVmax and tumor-to-background ratio of the former were higher than those of the latter (SUVmax: 14.5 ± 16.7 vs. 11.4 ± 13.6, P < 0.001; tumor-to-background ratio: 37.1 ± 42.3 vs. 23.1 ± 27.4, P < 0.001). The receiver-operating-characteristic curve analysis showed that the areas under the curve for PRIMARY score-predicted true-positive and false-positive lesions were significantly higher than those for the SUVmax of standard images (P = 0.015) and seemed higher than those for the SUVmax of delayed images (P = 0.257). [18F]AlF-thretide PET/CT showed a higher detection rate than multiparametric MRI for all intraprostatic foci (53.5% vs. 40.8%, P = 0.012) and clinically significant PCa (75.0% vs. 61.4%, P = 0.031). Conclusion: [18F]AlF-thretide PET/CT showed high diagnostic value for patients with primary PCa and can be used as an excellent imaging modality for preoperative evaluation of PCa patients.