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Objective:To investigate the clinical application of 68Ga-cyclo( L-arginylglycyl- L-α-aspartyl- D-tyrosyl-N6-(((4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)acetyl))- L-lysyl) (NODAGA-RGD) PET/CT to evaluate short-term efficacy of tyrosine kinase inhibitor (TKI) in distant metastatic differentiated thyroid cancer (dmDTC). Methods:From October 2019 to March 2023, 13 dmDTC patients (5 males, 8 females; age: 68(65, 69) years) from Nanjing First Hospital were retrospectively enrolled, of which 9 were clinically confirmed as radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and 4 were dmDTC without radioactive iodine treatment. All patients underwent 68Ga-NODAGA-RGD PET/CT to assess neovascularization of the target lesions (TL), and the SUV max and target background ratio (T/B) were recorded. After 3 months of TKI treatment (anrotinib ( n=9) or apatinib ( n=4)), change rates of the maximum diameter of TL and thyroglobulin (Tg) were measured. The correlation of SUV max, T/B and the change rate of the maximum diameter of TL were analyzed by Spearman rank correlation analysis. ROC curve analysis was performed for the effectiveness of the T/B and TKI therapy, and the difference of the remission rate of lesions was analyzed by Fisher exact test. Results:In 13 patients, 36 TL were measured by 68Ga-NODAGA-RGD PET/CT with SUV max of 5.44(3.43, 7.56) and T/B of 5.25(4.50, 7.23). The change rate of the maximum diameter of TL was -30%(-39%, -21%) and the change rate of Tg was -68%(-96%, -52%). T/B was negatively correlated with the change rate of the maximum diameter of TL after TKI therapy ( rs=-0.46, P=0.005), while SUV max was not correlated with the change rate of the maximum diameter of TL ( rs=0.03, P=0.883). ROC curve analysis showed that the optimal cut-off value for T/B was 4.95, with the AUC of 0.698, the sensitivity of 87.5%, and the specificity of 60.0%. Compared to lesions with T/B<4.95, those with T/B≥4.95 showed higher remission rate (2/14 vs 63.6%(14/22); P=0.006). After 3 months of TKI treatment, the disease control rate was 12/13. Conclusion:68Ga-NODAGA-RGD PET/CT can effectively reflect tumor neovascularization, predict efficacy of TKI therapy, and provide powerful imaging evidence for TKI therapy in dmDTC.
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Objective To investigate the clinical value of 18F-FDG PET/CT in diagnosing G3 NEN and compare it with 68Ga-DOTA-NOC PET/CT.Methods Twenty-three patients (12 males,11 females;average age (63± 12) years) diagnosed of NEN between January 2006 and November 2016 were retrospectively recruited in this study:11 patients with gastroenteropancreatic NEN (GEP-NEN),10 with G3 NEN in lungs,1 with malignant pheochromocytoma and 1 with G3 NEN of unknown primary site.All patients underwent 18F-FDG PET/CT for staging and evaluation of biological behavior,and 9 of them also underwent 68Ga-DOTA-NOC PET/CT within 1 week.Image interpretation was analyzed by visual and semi-quantitative analysis,and SUVmax was calculated.Results All 23 cases showed positive results on 18F-FDG PET/CT (100％,23/23),with primary tumor SUVmax 10.56±3.94.Compared with 18F-FDG PET/CT,the positive detection rate of 68Ga-DOTA-NOC PET/CT was lower (6/9 vs 9/9),with primary tumor SUVmax 14.24± 10.00.There were 22 patients with distant metastasis.The most frequent metastatic sites associated with G3 NEN in lungs were lymph nodes and bones,while those with GEP-NEN were lymph nodes and the liver.In one patient with non-functional NEN,some metastatic lesions showed negative results on 18F-FDG PET/CT but positive results on 68 Ga-DOTA-NOC PET/CT.Conclusions 18 F-FDG PET/CT has higher diagnostic ability for G3 NEN and may serve as a useful tool for evaluating biological behavior of G3 NEN.68Ga-DOTA-NOC PET/CT is valuable as a complementary diagnostic tool in a small proportion of high differentiated G3 NEN.
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Objective To assess the role of 68Ga-N,N′-bis(2-hydroxy-5-(carboxyethyl)benzyl) ethylenediamine-N,N′-diacetic acid(HBED-CC)-(Ahx)Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L, Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesion-based analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging, MRI).χ2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine, with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients, liver metastasis in 2 patients (5 lesions), and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver, lymph node and bone metastases were 15.06±2.77, 7.54±5.20, 19.01±16.96, respectively.The diagnostic sensitivity, specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30%(52/54) vs 61.11%(33/54), 3/3 vs 1/3, 96.49%(55/57) vs 59.65%(34/57).The sensitivities and accuracies of the two modalities were significantly different(χ2=19.943, 22.593, both P<0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC, suggesting that it is of great value for the clinical management and treatment.
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Objective To investigate the value of integrin αvβ3 targeted microSPECT/CT imaging with 99 Tcm-3P4-RGD2 as a radiotracer in tumor anti-angiogenesis therapy .Methods Animal models bearing glioma and prostate cancer xenografts were established by subcutaneously injecting tumor cells U87MG and PC-3 in nude mice.Anti-angiogensis therapy with Avastin was administered via intraperitoneal injection when the tumor diameter reached 6 to 7 mm while saline was served as control group . MicroSPECT/CT imaging was performed with 99 Tcm-3P4-RGD2 as radiotracer one day before and 3, 5, 10, 15 days after Avastin administration .Tumor volume and tumor uptake of 99 Tcm-3P4-RGD2 , expressed as percentage of injected dose (%ID) or %ID per gram (%ID/g) were measured and calculated based on microSPECT/CT.Mice basic condition was monitored and tumor xenograft was harvested in one tumor bearing nude mouse after its sacrifice at each imaging time point .Results Tumor volume of U87MG glioma in the administration group was significantly smaller than that of non-administration control group at 10 d after Avastin adminstration ( t=5.81, P0.05).The uptake of 99Tcm-3P4-RGD2 (%ID/g) in U87MG group was higher than that in PC-3 group before Avastin administration ( t=10.48, P<0.05), and it decreased to a value less than control ( t =3.26, P <0.05) at 3 d after Avastin administration and continually reduced at longer time after administration .PC-3 tumor had less uptake of 99 Tcm-3P4-RGD2 in both Avastin administration group and its control group .The pathologic results revealed on that the decrease of tumor integrin β3 expression in U87MG treatment group was mainly on the endothelial cells of the neovessel .Linear relationship was verified between tumor uptake (%ID/g ) and integrin β3 expression (y=0.499 1x-0.243 8, R2 =0.811 7).Conclusions Complete inhibition of integrin is demonstrated early after Avastin administration .99 Tcm-3P4-RGD2 microSPECT/CT imaging, assessing the expression level of integrin αvβ3 level by quantification of tumor uptake of 99 Tcm-3P4-RGD2 , is probably an important method to reflect the early therapeutic effect of tumor anti -angiogensis .
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Objective To assess the role of 68Ga-N,N'-bis (2-hydroxy-5-(carboxyethyl) benzyl) ethylenediamine-N,N'-diacetic acid(HBED-CC)-(Ahx) Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L,Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesionbased analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging,MRI).x2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine,with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients,liver metastasis in 2 patients (5 lesions),and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver,lymph node and bone metastases were 15.06±2.77,7.54±5.20,19.01± 16.96,respectively.The diagnostic sensitivity,specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30％(52/54) vs 61.11％(33/54),3/3 vs 1/3,96.49％ (55/57) vs 59.65％ (34/57).The sensitivities and accuracies of the two modalities were significantly different(x2=19.943,22.593,both P＜0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC,suggesting that it is of great value for the clinical management and treatment.
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Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. NETs can produce a variety of metabolically active substances (hormones and amines) leading to distinct clinical syndromes. This review will discuss the imaging techniques for the diagnosis of GEP-NETs including ultrasonography, CT, MRI and ultrasound endoscope. In this article, Gallium-68 labeled peptide binding to G protein coupled receptor including SSTR, CCKR1 and GLP1R is addressed, and the application of Gallium-68 labeled somatostin analogues and PET-CT for diagnosis of GEP-NETs is evaluated. In conclusion, Gallium-68 labeled peptide and molecular imaging will play important roles in diagnosis, prognosis and therapeutic strategy development of GEP-NETs.