Phase 1 Study of No-Carrier Added 177Lu-DOTATATE (SNU-KB-01) in Patients with Somatostatin Receptor–Positive Neuroendocrine Tumors: The First Clinical Trial of Peptide Receptor Radionuclide Therapy in Korea / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#To provide a wider choice of treatment opportunities for patients with neuroendocrine tumor (NET) in Korea, we have conducted a phase 1, open-label, single-arm, dose-escalation study of SNU-KB-01, a no-carrier added (NCA) 177Lu-labeled DOTATATE. @*Materials and Methods@#Seven patients with inoperable, progressive, metastatic, or locally advanced, somatostatin receptor-positive NET with Ki67 index ≤ 20% were enrolled according to the rolling six design. The study consisted of two cohorts to receive 4 cycles of SNU-KB-01 every 8 weeks for the first dose of 5.55 GBq (n=3) and 7.40 GBq (n=4). We assessed the incidence of dose-limiting toxicity (DLT) and adverse event, absorbed dose of kidneys and bone marrow, and objective tumor response. @*Results@#Seven patients completed 4 cycles (21.3-30.1 GBq total dose) of SNU-KB-01. The mean absorbed doses to kidneys and bone marrow were 0.500 mGy/MBq and 0.053 mGy/MBq, respectively, and the total body effective dose was 0.115 mSv/MBq. No DLT was observed and the maximum tolerated dose was 7.40 GBq/cycle. Grade 3 thrombocytopenia occurred in one patient, but no other grade 3 or 4 major hematologic or renal toxicity was observed. The best objective response to SNU-KB-01 was partial response. Overall response rate was 42.9% and disease control rate was 85.7%. @*Conclusion@#Treatment with 4 cycles of SNU-KB-01 was well tolerated and resulted in control of disease in most of the patients. Our results indicate SNU-KB-01, an NCA 177Lu-labeled DOTATATE, as a potentially safe and efficacious treatment option for NET patients in Korea.

Phase I Clinical Trial of Prostate-Specific Membrane Antigen-Targeting 68 Ga-NGUL PET/CT in Healthy Volunteers and Patients with Prostate Cancer

Objective@#68 Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N’,N’’-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68 Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68 Ga-NGUL in healthy volunteers and the lesion detection rate of 68 Ga-NGUL in patients with prostate cancer. @*Materials and Methods@#We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68 Ga-NGUL (2 MBq/kg; 96–165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68 Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. @*Results@#All 12 participants (six healthy adults aged 31–32 years and six prostate cancer patients aged 57–81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68 Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68 Ga-NGUL PET/CT or conventional imaging. Among them, 68 Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. @*Conclusion@#68 Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68 Ga-NGUL is a valuable option for prostate cancer imaging.

Spleen Scan for 68Ga-DOTATOC PET-Positive Pancreatic Tail Lesion: Differential Diagnosis of Neuroendocrine Tumor from Accessory Spleen / 대한핵의학회잡지

68Ga-DOTATOC PET/CT is widely used as a functional imaging technique in the detection and characterization of neuroendocrine tumors (NETs). Pancreatic NET and intrapancreatic accessory spleen (IPAS) have similar radiologic characteristics in anatomical imaging and usually show high uptake of 68Ga-DOTATOC. Thus, it is challenging to make a differential diagnosis between NET and IPAS when the tumor-like lesion is located in the pancreatic tail. Here, we present a case of 68Ga-DOTATOC PET-positive pancreatic tail lesion with high arterial enhancement on CT and MRI. Since 99mTc-labeled damaged red blood cell does not accumulate on NET, a negative spleen scan finding was a crucial diagnostic step to decide surgical resection, which was histologically proven as insulinoma. Our case shows a promising role of additional use of spleen scan with SPECT/CT for the differential diagnosis of 68Ga-DOTATOC PET-positive pancreatic NET from the accessory spleen.

Basal and Acetazolamide Brain Perfusion SPECT in Internal Carotid Artery Stenosis / 대한핵의학회잡지

Internal carotid artery (ICA) stenosis including Moyamoya disease needs revascularization when hemodynamic insufficiency is validated. Vascular reserve impairment was the key to find the indication for endarterectomy/bypass surgery in the atherosclerotic ICA stenosis and to determine the indication, treatment effect, and prognosis in Moyamoya diseases. Vascular reserve was quantitatively assessed by 1-day split-dose I-123 IMP basal/acetazolamide SPECT in Japan or by Tc-99m HMPAO SPECT in other countries using qualitative or semi-quantitative method. We summarized the development of 1-day basal/ acetazolamide brain perfusion SPECT for ICA stenosis, both quantitative and qualitative methods, and their methodological issues regarding (1) acquisition protocol; (2) qualitative assessment, either visual or deep learning-based; (3) clinical use for atherosclerotic ICA steno-occlusive diseases and mostly Moyamoya diseases; and (4) their impact on the choice of treatment options. Trials to use CT perfusion or perfusion MRI using contrast materials or arterial spin labeling were briefly discussed in their endeavor to use basal studies alone to replace acetazolamide-challenge SPECT. Theoretical and practical issues imply that basal perfusion evaluation, no matter how much sophisticated, will not disclose vascular reserve. Acetazolamide rarely causes serious adverse reactions but included fatality, and now, we need to monitor patients closely in acetazolamide-challenge studies.

Comparative Analysis of Lung Perfusion Scan and SPECT/CT for the Evaluation of Functional Lung Capacity / 대한핵의학회잡지

PURPOSE: This study aimed to compare lung perfusion scan with single photon emission computed tomography/computed tomography (SPECT/CT) for the evaluation of lung function and to elucidate the most appropriate modality for the prediction of postoperative lung function in patients with lung cancer.METHODS: A total of 181 patients underwent Tc-99m macroaggregated albumin lung perfusion scan and SPECT/CT to examine the ratio of diseased lung and diseased lobe. Forty-one patients with lung cancer underwent both preoperative and postoperative pulmonary function tests within 1 month to predict postoperative pulmonary function. Predicted postoperative forced expiratory volume in 1 s (ppoFEV₁) was calculated by the % radioactivity of lung perfusion scan and SPECT, and the % volume of the residual lung, assessed on CT.RESULTS: The ratios of diseased lung as seen on lung perfusion scan and SPECT showed significant correlation, but neither modality correlated with CT. The ratios of the diseased lung and diseased lobe based on CT were higher than the ratios based on either perfusion scan or SPECT, because CT overestimated the function of the diseased area. The lobar ratio of both upper lobes was lower based on the perfusion scan than on SPECT but was higher for both lower lobes. Actual postoperative FEV₁ showed significant correlation with ppoFEV₁ based on lung perfusion SPECT and perfusion scan.CONCLUSIONS: We suggest SPECT/CT as the primary modality of choice for the assessment of the ratio of diseased lung area. Both perfusion scan and SPECT/CT can be used for the prediction of postoperative lung function.

Amyloid PET Quantification Via End-to-End Training of a Deep Learning / 대한핵의학회잡지

PURPOSE: Although quantification of amyloid positron emission tomography (PET) is important for evaluating patients with cognitive impairment, its routine clinical use is hampered by complicated preprocessing steps and required MRI. Here, we suggested a one-step quantification based on deep learning using native-space amyloid PET images of different radiotracers acquired from multiple centers.METHODS: Amyloid PET data of the Alzheimer Disease Neuroimaging Initiative (ADNI) were used for this study. A training/validation consists of 850 florbetapir PET images. Three hundred sixty-six florbetapir and 89 florbetaben PET images were used as test sets to evaluate the model. Native-space amyloid PET images were used as inputs, and the outputs were standardized uptake value ratios (SUVRs) calculated by the conventional MR-based method.RESULTS: The mean absolute errors (MAEs) of the composite SUVR were 0.040, 0.060, and 0.050 of training/validation and test sets for florbetapir PETand a test set for florbetaben PET, respectively. The agreement of amyloid positivity measured by Cohen's kappa for test sets of florbetapir and florbetaben PET were 0.87 and 0.89, respectively.CONCLUSION: We suggest a one-step quantification method for amyloid PET via a deep learning model. The model is highly reliable to quantify the amyloid PET regardless of multicenter images and various radiotracers.

Minimum Standardized Uptake Value from Quantitative Bone Single-Photon Emission Computed Tomography/Computed Tomography for Evaluation of Femoral Head Viability in Patients with Femoral Neck Fracture / 대한핵의학회잡지

PURPOSE: Bone single-photon emission computed tomography/computed tomography (SPECT/CT) has been widely used for evaluation of femoral head viability in patients with femoral neck fracture. The current study aimed to investigate utility of standardized uptake value (SUV) from quantitative bone SPECT/CT for assessment of femoral head viability.METHODS: From March 2015 to November 2018, quantitative bone SPECT/CT was performed in 9 patients with non-viable femoral head post femoral neck fracture and in 31 controls. Maximum (SUV(max)), mean (SUVmean), and minimum standardized uptake values (SUVmin) were measured over femoral head and neck. Mann-Whitney U test with Bonferroni correction was used to compare SUVs of ipsilateral and contralateral femurs from femoral neck fracture patients with those of control femurs.RESULTS: As for femoral head viability, SUV(max) and SUVmean were not significantly decreased in non-viable femoral heads compared to those in controls. Only the SUVmin was significantly reduced in non-viable femoral heads (mean ± standard deviation, 0.57 ± 0.38) than in controls (0.95 ± 0.26, p = 0.006) and contralateral femoral heads (1.36 ± 0.59, p = 0.008). The cutoff SUVmin of 0.61 (g/mL) yielded a sensitivity of 77.8% and specificity of 87.1% for detection of non-viable femoral heads (p = 0.006). Contralateral femoral necks of the femoral neck fracture patients showed significantly higher SUVmean and SUVmin (3.17 ± 1.20 and 1.64 ± 0.63) than those of controls (2.32 ± 0.53 and 1.04 ± 0.27; p = 0.021 and p = 0.002, respectively), which seemed to reflect weight bearing effect or metabolic derangement.CONCLUSIONS: The non-viable femoral heads from the femoral neck fracture showed significantly reduced SUVmin. Quantitative bone SPECT/CT holds promise for objective evaluation of femoral head viability.

Amyloid PET Quantification Via End-to-End Training of a Deep Learning / 대한핵의학회잡지

PURPOSE@#Although quantification of amyloid positron emission tomography (PET) is important for evaluating patients with cognitive impairment, its routine clinical use is hampered by complicated preprocessing steps and required MRI. Here, we suggested a one-step quantification based on deep learning using native-space amyloid PET images of different radiotracers acquired from multiple centers.@*METHODS@#Amyloid PET data of the Alzheimer Disease Neuroimaging Initiative (ADNI) were used for this study. A training/validation consists of 850 florbetapir PET images. Three hundred sixty-six florbetapir and 89 florbetaben PET images were used as test sets to evaluate the model. Native-space amyloid PET images were used as inputs, and the outputs were standardized uptake value ratios (SUVRs) calculated by the conventional MR-based method.@*RESULTS@#The mean absolute errors (MAEs) of the composite SUVR were 0.040, 0.060, and 0.050 of training/validation and test sets for florbetapir PETand a test set for florbetaben PET, respectively. The agreement of amyloid positivity measured by Cohen's kappa for test sets of florbetapir and florbetaben PET were 0.87 and 0.89, respectively.@*CONCLUSION@#We suggest a one-step quantification method for amyloid PET via a deep learning model. The model is highly reliable to quantify the amyloid PET regardless of multicenter images and various radiotracers.

Comparative Analysis of Lung Perfusion Scan and SPECT/CT for the Evaluation of Functional Lung Capacity / 대한핵의학회잡지

PURPOSE@#This study aimed to compare lung perfusion scan with single photon emission computed tomography/computed tomography (SPECT/CT) for the evaluation of lung function and to elucidate the most appropriate modality for the prediction of postoperative lung function in patients with lung cancer.@*METHODS@#A total of 181 patients underwent Tc-99m macroaggregated albumin lung perfusion scan and SPECT/CT to examine the ratio of diseased lung and diseased lobe. Forty-one patients with lung cancer underwent both preoperative and postoperative pulmonary function tests within 1 month to predict postoperative pulmonary function. Predicted postoperative forced expiratory volume in 1 s (ppoFEV₁) was calculated by the % radioactivity of lung perfusion scan and SPECT, and the % volume of the residual lung, assessed on CT.@*RESULTS@#The ratios of diseased lung as seen on lung perfusion scan and SPECT showed significant correlation, but neither modality correlated with CT. The ratios of the diseased lung and diseased lobe based on CT were higher than the ratios based on either perfusion scan or SPECT, because CT overestimated the function of the diseased area. The lobar ratio of both upper lobes was lower based on the perfusion scan than on SPECT but was higher for both lower lobes. Actual postoperative FEV₁ showed significant correlation with ppoFEV₁ based on lung perfusion SPECT and perfusion scan.@*CONCLUSIONS@#We suggest SPECT/CT as the primary modality of choice for the assessment of the ratio of diseased lung area. Both perfusion scan and SPECT/CT can be used for the prediction of postoperative lung function.

Minimum Standardized Uptake Value from Quantitative Bone Single-Photon Emission Computed Tomography/Computed Tomography for Evaluation of Femoral Head Viability in Patients with Femoral Neck Fracture / 대한핵의학회잡지

PURPOSE@#Bone single-photon emission computed tomography/computed tomography (SPECT/CT) has been widely used for evaluation of femoral head viability in patients with femoral neck fracture. The current study aimed to investigate utility of standardized uptake value (SUV) from quantitative bone SPECT/CT for assessment of femoral head viability.@*METHODS@#From March 2015 to November 2018, quantitative bone SPECT/CT was performed in 9 patients with non-viable femoral head post femoral neck fracture and in 31 controls. Maximum (SUV(max)), mean (SUVmean), and minimum standardized uptake values (SUVmin) were measured over femoral head and neck. Mann-Whitney U test with Bonferroni correction was used to compare SUVs of ipsilateral and contralateral femurs from femoral neck fracture patients with those of control femurs.@*RESULTS@#As for femoral head viability, SUV(max) and SUVmean were not significantly decreased in non-viable femoral heads compared to those in controls. Only the SUVmin was significantly reduced in non-viable femoral heads (mean ± standard deviation, 0.57 ± 0.38) than in controls (0.95 ± 0.26, p = 0.006) and contralateral femoral heads (1.36 ± 0.59, p = 0.008). The cutoff SUVmin of 0.61 (g/mL) yielded a sensitivity of 77.8% and specificity of 87.1% for detection of non-viable femoral heads (p = 0.006). Contralateral femoral necks of the femoral neck fracture patients showed significantly higher SUVmean and SUVmin (3.17 ± 1.20 and 1.64 ± 0.63) than those of controls (2.32 ± 0.53 and 1.04 ± 0.27; p = 0.021 and p = 0.002, respectively), which seemed to reflect weight bearing effect or metabolic derangement.@*CONCLUSIONS@#The non-viable femoral heads from the femoral neck fracture showed significantly reduced SUVmin. Quantitative bone SPECT/CT holds promise for objective evaluation of femoral head viability.