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

ABSTRACT: A 53-year-old man with newly diagnosed nasopharyngeal carcinoma (NPC) underwent 99mTc-MDP bone scintigraphy for the potential bone metastases, and paired 68Ga-DOTATATE and 68Ga-FAPI PET/CT for initial staging. 68Ga-DOTATATE PET/CT identified 2 abnormal foci with increased tracer uptake in the cervical vertebra and the ilium, whereas 68Ga-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 68Ga-DOTATATE PET/CT, was also a bone metastasis. This case highlighted the potential superiority of 68Ga-DOTATATE in NPC.

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.

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.

[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 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

ABSTRACT 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.

Clinical value of [18F]F-FDG PET/CT in patients with suspected paraneoplastic dermatoses: Diagnostic performance and impact on clinical management.

PURPOSE: We retrospectively evaluate the diagnostic performance of 2-deoxy-2[18F]fuoro-D-glucose([18F]F-FDG) PET/CT and its impact on clinical management in patients with suspected paraneoplastic dermatoses (PD). MATERIALS AND METHODS: From an institutional PET/CT database (2014-2022), we retrospectively analyzed patients who were clinically suspected with PD and underwent [18F]F-FDG PET/CT for screening an underlying malignancy. For all scans, positive mucocutaneous lesions and PET-indicated malignancies were assessed, and the degree of FDG avidity among different dermatoses were quantified. The final diagnoses of dermatoses and neoplasms were based on pathologic results, international diagnostic standard and follow-up. We assessed the recommended and applied therapies before and after [18F]F-FDG PET/CT and noted whether the patient management changed on the basis of the [18F]F-FDG PET/CT results. RESULTS: We analyzed 60 patients with 10 types of dermatoses in this study. Finally, 19 of the 60 patients who had both of specific dermatosis and contemporaneous neoplasm were diagnosed with PD. [18F]F-FDG PET could identify the underlying neoplasms in 18/19 (94.7%) PD patients, and led to a change of the management in 9/19 (47.4%) PD patients. In addition, the mucocutaneous manifestations of [18F]F-FDG PET/CT associated with several specific dermatoses were characteristic. CONCLUSIONS: This study highlighted the value of [18F]F-FDG PET/CT as a useful tool for evaluation of patients with suspected PD to unveil the underlying culprit tumor, and profoundly supports the clinical management of PD patients.

68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT for the Early and Late Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Prospective Study.

68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT has demonstrated promising clinical results, with a higher SUVmax and tumor-to-background ratio (TBR) in breast cancer (BC) patients than 18F-FDG PET/CT. Here, we aimed to evaluate the suitability of 68Ga-FAPI PET/CT for the early and late prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in BC. Methods: Twenty-two consecutive patients with newly diagnosed BC and an indication for NAC were prospectively included. All patients underwent standard chemotherapy and 68Ga-FAPI PET/CT at baseline, after 2 cycles of NAC (PET2), and 1 wk before surgery (PET3). SUVmax was measured in the primary tumor region and positive regional lymph nodes. The expression of fibroblast activation protein in the primary lesion was analyzed by immunohistochemistry. Results: Seven patients (31.8%) achieved a pathologic complete response (pCR), and 15 (68.2%) had residual tumors. Thirteen patients (59.1%) showed concentric withdrawal of the primary tumor, and 9 (40.9%) showed diffuse withdrawal. Between PET2 and PET3, the ΔSUVmax of the primary tumor (R 2 = 0.822; P = 0.001) and metastatic lymph nodes (R 2 = 0.645; P = 0.002) were significantly correlated. The absolute values of SUVmax and TBR at PET2 and PET3 were lower in patients with pCR than in those without pCR (P < 0.05). Moreover, a larger ΔSUVmax at any time point was strongly associated with pCR (P < 0.05). Similar downward trends in SUVmax, TBR, and ΔSUVmax were observed in the pattern of primary tumor reduction. For predicting pCR, the optimal cutoff values for ΔSUVmax after 2 chemotherapy cycles, ΔSUVmax before surgery, TBR after 2 chemotherapy cycles, and TBR before surgery of the primary tumor were 3.4 (area under the curve [AUC], 0.890), 1.1 (AUC, 0.978), -63.8% (AUC, 0.879), -90.8% (AUC, 0.978), 7.6 (AUC, 0.848), and 1.4 (AUC, 0.971), respectively. Immunohistochemistry showed that the SUVmax and TBR of 68Ga-FAPI PET/CT were positively correlated with fibroblast activation protein expression (P < 0.001 for both). Conclusion: Assessment of early changes in 68Ga-FAPI uptake during NAC by 68Ga-FAPI PET/CT can predict pCR and primary tumor concentric withdrawal in BC patients. 68Ga-FAPI PET/CT has great potential for the early and late prediction of the pathologic response to NAC in BC.

68 Ga-PSMA PET/CT in Hepatic Metastasis From Pancreatic Neuroendocrine Tumor.

ABSTRACT: A 53-year-old man underwent both 18 F-FDG and 68 Ga-PSMA PET/CT to evaluate a mass in the left upper abdomen. The scans demonstrated intense uptake of both 18 F-FDG and 68 Ga-PSMA in the mass. However, a nodule in the left lobe of the liver showed increased uptake of 68 Ga-PSMA, which was not FDG avid. Histopathological examination after surgical resection of the mass confirmed the diagnosis of pancreatic neuroendocrine tumor (G2). Subsequently, 68 Ga-DOTATATE PET/CT demonstrated intense radioactivity of the nodule in the left lobe of the liver consistent with hepatic metastasis from neuroendocrine tumor.

68 Ga-LNC-1007 PET/CT Imaging in a Patient With Renal Cell Carcinoma Compared With 68 Ga-PSMA-11 PET/CT.

ABSTRACT: A 57-year-old man was incidentally found with 3 lesions located in bilateral kidneys, which were finally diagnosed as renal cell carcinoma (RCC) by postoperative pathology. 68 Ga-LNC-1007, also denoted as 68 Ga-FAPI-RGD, was synthesized from fibroblast activation protein inhibitor-02 (FAPI-02) and cyclic arginine-glycine-aspartate (RGD), which could target both FAP and integrin α v ß 3 . RCC lesions demonstrated only slight 68 Ga-PSMA uptake, but intense tracer uptake on 68 Ga-LNC-1007 PET/CT. This case demonstrates the potential value of 68 Ga-LNC-1007 PET/CT for the evaluation of RCC.

A Head-to-Head Comparison of 68Ga-LNC1007 and 2-18F-FDG/68Ga-FAPI-02 PET/CT in Patients With Various Cancers.

OBJECTIVES: This head-to-head comparison study was designed to investigate the radiotracer uptake and clinical feasibility of using 68Ga-LNC1007, to detect the primary and metastatic lesions in patients with various types of cancer, and to compare the results with those of 2-18F-FDG PET/CT and 68Ga-FAPI-02 PET/CT. PATIENTS AND METHODS: Sixty-one patients with 10 different kinds of cancers were enrolled in this study. Among them, 50 patients underwent paired 68Ga-LNC1007 and 2-18F-FDG PET/CT, and the other 11 patients underwent paired 68Ga-LNC1007 and 68Ga-FAPI-02 PET/CT. The final diagnosis was based on histopathological results and diagnostic radiology. Immunohistochemistry for FAP and integrin αvß3 was performed in 24 primary tumors. RESULTS: 68Ga-LNC1007 PET/CT detected all 55 primary tumors, whereas 2-18F-FDG PET/CT was visually positive for 45 primary tumors (P = 0.002). Furthermore, subgroup analysis showed that 68Ga-LNC1007 PET/CT was superior to 2-18F-FDG PET/CT in diagnosing renal cell carcinomas and hepatocellular carcinomas. For metastatic tumors, 68Ga-LNC1007 PET/CT revealed more PET-positive lesions and higher SUVmax for skeletal metastases and peritoneal metastases compared with 2-18F-FDG. The SUVmax and tumor-to-background ratio of primary tumors on 68Ga-LNC1007 PET/CT were much higher than those on 68Ga-FAPI-02 PET/CT, the same was also observed for metastatic tumors. Immunohistochemical results showed that the SUVmean quantified from 68Ga-LNC1007 PET was correlated with FAP expression level (r = 0.564, P = 0.005). CONCLUSIONS: 68Ga-LNC1007 is a promising new diagnostic PET tracer for imaging of various kinds of malignant lesions. It may be a better alternative to 2-18F-FDG for diagnosing renal cell carcinoma, hepatocellular carcinoma, skeletal metastases, and peritoneal metastases.

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.

Head-to-head comparisons of 68Ga-PSMA-11 and 18F-FDG PET/CT in evaluating patients with upper tract urothelial carcinoma: a prospective pilot study.

PURPOSE: To prospectively compare the uptake of 68Ga-prostate specific membrane antigen (68Ga-PSMA)-11 and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in upper tract urothelial carcinoma (UTUC) and investigate the correlation between radiological parameters and pathological features of UTUC. METHODS: Clinicopathologic and imaging data were collected from 10 UTUC patients who underwent preoperative 68Ga-PSMA-11 and 18F-FDG PET/CT scans. The diagnostic capabilities of both imaging techniques were analyzed and compared in UTUC. Angiogenesis in the malignancies was assessed using Chalkley counting and the expression of folate hydrolase 1 (FOLH1) and glucose transporter 1 (GLUT1) in UTUC were evaluated in the surgical specimens. Double immunofluorescence staining of PSMA and CD34 was used to examine tumor neovascularization. Tracer uptake and expression were compared and explored. Additionally, 10 patients with clear cell renal cell carcinoma (ccRCC) were included for prospective, comparative research. RESULTS: Ten UTUC patients with 12 malignant lesions and another 10 ccRCC patients were included. 18F-FDG PET/CT demonstrated a more effective detection of UTUC foci compared to 68Ga-PSMA-11 PET/CT (the SUVmax of 18.48 ± 6.73 vs. 4.38 ± 1.45, P < 0.01). Immunohistochemical analysis revealed a statistically significant difference in the expression of PSMA and GLUT1 in UTUC (P = 0.048), with higher pathological grades showing more intense GLUT1 staining than PSMA (75% vs. 12.5%). The Chalkley counting of angiogenesis in ccRCC was significantly higher than that in UTUC (229.34 vs. 71.67), which was proportional to 68Ga-PSMA-11 PET/CT SUVmax (both P < 0.05). CONCLUSION: 18F-FDG PET/CT holds better clinical potential for evaluating UTUC and detecting lymph node metastasis compared to 68Ga-PSMA-11 PET/CT, likely due to the relatively scant expression of FOLH1 in tumor neovascular endothelium while the abundant expression of GLUT1 in malignancy. Furthermore, the lower neovascular density in UTUC should not be overlooked.

Primary Pancreatic Lymphoma Masquerading as Carcinoma on 18 F-FDG PET/CT.

ABSTRACT: A 76-year-old man with yellowish discoloration of sclera and skin for 2 months was referred to 18 F-FDG PET/CT for metabolic characterization of the mass in the pancreas. The images showed intense FDG uptake in the head of the pancreas, as well as a lymph nodal mass in the hepatic hilar region, which was consistent with pancreatic malignancy. Histopathologic findings showed characteristic findings of diffuse large B-cell lymphoma with no evidence of adenocarcinoma.

Head-to-Head Comparison of 68Ga-NODAGA-JR11 and 68Ga-DOTATATE PET/CT in Patients with Metastatic, Well-Differentiated Neuroendocrine Tumors: Interim Analysis of a Prospective Bicenter Study.

The current study aimed to compare 68Ga-NODAGA-Cpa-cyclo(d-Cys-amino-Phe-hydroorotic acid-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)-d-Tyr-NH2 (JR11) and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: A prospective bicenter study aimed at enrolling 100 patients with histologically proven, metastatic or unresectable, well-differentiated neuroendocrine tumors was conducted. The first 48 patients represented the study cohort. Each patient received 68Ga-DOTATATE on the first day and 68Ga-NODAGA-JR11 on the second day. Whole-body PET/CT scans were performed at 40-60 min after injection. Normal-organ uptake, lesion numbers, lesion uptake, and sensitivity were compared. The potential impact on clinical management was also determined. Results: Overall, 68Ga-NODAGA-JR11 demonstrated lower background uptake in normal organs. Compared with 68Ga-DOTATATE, 68Ga-NODAGA-JR11 detected significantly more liver lesions (673 vs. 584, P = 0.002). The target-to-background ratio of liver lesions was significantly higher on 68Ga-NODAGA-JR11 (6.4 ± 8.7 vs. 3.1 ±2.6, P = 0.000). Comparable uptake was observed for primary tumors, bone lesions, and lymph node metastases. In total, 180 lesions were detected on conventional imaging in 15 patients; 165 and 139 lesions of them were positive on 68Ga-NODAGA-JR11 and 68Ga-DOTATATE, leading to a sensitivity of 91.7% and 77.2%, respectively. In 14.5% (7/48) of patients, 68Ga-NODAGA-JR11 PET might have a potential impact on clinical management. Conclusion: 68Ga-NODAGA-JR11 shows better sensitivity and a higher target-to-background ratio than 68Ga-DOTATATE. The detection of more lesions by the antagonist may have a potential impact on clinical management in a subgroup of patients.

68Ga-FAPI Versus 18F-FDG PET/CT in Evaluating Newly Diagnosed Breast Cancer Patients: A Head-to-Head Comparative Study.

PURPOSE: This study aimed to compare the performance of 68Ga-FAPI and 18F-FDG PET/CT in the evaluation of patients with newly diagnosed breast cancer. METHODS: Thirty-four women with newly diagnosed breast cancer who underwent both 68Ga-FAPI and 18F-FDG PET/CT within 1 week were prospectively included in the study. The imaging characteristics of primary lesions, diagnostic efficiency of lymph node metastasis (LNM), and accuracy of N stage evaluation between 2 PET/CTs were compared. RESULTS: 68Ga-FAPI showed higher SUVmax (11.06 ± 5.48 vs 8.33 ± 6.07, P = 0.02) and tumor-to-background ratio (15.32 ± 10.33 vs 8.25 ± 5.51, P < 0.001) than 18F-FDG in primary tumors. 68Ga-FAPI SUVmax was positively correlated with the pathological grade of the primary lesions and the final stage of the patients (P < 0.001). The specificity and accuracy of 68Ga-FAPI was higher than that of 18F-FDG in the diagnosis of LNMs on patient-based and lesion-based analysis (P < 0.001). The accuracy for the evaluation of N stage and N0 axillar status was 91.2% (31/34) and 85.7% (12/14) for 68Ga-FAPI, and 73.5% (25/34) and 42.9% (6/14) for 18F-FDG, respectively. CONCLUSIONS: The 68Ga-FAPI SUVmax was positively correlated with the pathological grade of the primary lesions and the final stage of the patients. 68Ga-FAPI PET/CT has higher accuracy than 18F-FDG in the evaluation of N stage, especially N0 axillar status, which is helpful to improve the treatment strategy for breast cancer patients.

68Ga-FAPI and 18F-FDG PET/CT Images of a Patient With Rosai-Dorfman Disease With Liver Involvement.

ABSTRACT: Rosai-Dorfman disease is a rare non-Langerhans cell histiocytosis that is histopathologically characterized by the accumulation of CD68-positive and S100-positive histiocytes. The pathological changes are mostly discovered in lymph nodes. We report a case of Rosai-Dorfman disease with liver and bone marrow involvement. In this case, 18F-FDG PET/CT revealed FDG avidity in multiple lymph nodes, liver, and bone marrow. 68Ga-FAPI PET/CT showed higher uptake of 68Ga-FAPI than that of 18F-FDG in the same lesions. The findings of 68Ga-FAPI PET/CT in this patient highlighted the potential value of 68Ga-FAPI for staging in Rosai-Dorfman disease.

Synthesis, preclinical evaluation and radiation dosimetry of a dual targeting PET tracer [68Ga]Ga-FAPI-RGD.

To enhance tumor uptake and retention, we designed and developed bi-specific heterodimeric radiotracers targeting both FAP and αvß3, [68Ga]Ga-FAPI-RGD. The present study aimed to evaluate the specificity, pharmacokinetics, and dosimetry of [68Ga]Ga-FAPI-RGD by preclinical and preliminary clinical studies. Methods: FAPI-RGD was designed and synthesized with the quinoline-based FAPI-02 and the cyclic RGDfK peptide. Preclinical pharmacokinetics were determined in Panc02 xenograft model using microPET and biodistribution experiments. The safety and effective dosimetry of [68Ga]Ga-FAPI-RGD was evaluated in 6 cancer patients, and compared with 2-[18F]FDG imaging. Results: The [68Ga]Ga-FAPI-RGD had good stability in saline for at least 4 h, and showed favorable binding affinity and specificity in vitro and in vivo. Compared to [68Ga]Ga-FAPI-02 and [68Ga]Ga-RGDfK, the tumor uptake and retention of [68Ga]Ga-FAPI-RGD were very much enhanced than its monomeric counterparts at all the time points examined by microPET imaging. A total of 6 patients with various malignant tumors were prospectively enrolled. The effective dose of [68Ga]Ga-FAPI-RGD was 1.94E-02 mSv/MBq. The biodistribution of [68Ga]Ga-FAPI-RGD from 0 to 2 h after injection demonstrated rapid and high tumor uptake, prolonged tumor retention, and high tumor-to-background ratios (TBRs) which further increased over time. No significant difference in mean SUVmax of [68Ga]Ga-FAPI-RGD and 2-[18F]FDG was present in primary tumors (8.9±3.2 vs. 10.3 ± 6.9; p = 0.459). Conclusion: The dual targeting PET tracer [68Ga]Ga-FAPI-RGD showed significantly improved tumor uptake and retention, as well as cleaner background over 68Ga-labeled FAPI and RGD monospecific tracers. The first-in-human biodistribution study showed high TBRs over time, suggesting high diagnostic performance and favorable tracer kinetics for potential therapeutic applications.