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Purpose: We aimed to compare the diagnostic performance of 68Ga-FAPI-04 (FAPI) in comparison to 68Ga-DOTATATE (SSTR) PET/CT for patients presenting with recurrent medullary thyroid carcinoma (MTC)., Patients and Methods: Sixteen MTC patients with elevated calcitonin levels (>150 pg/mL) underwent FAPI and SSTR PET/CT. Two nuclear medicine physicians evaluated all images, categorizing lesions into locoregional metastases, mediastinal lymph nodes (LNs), liver, and bone metastases. SUVmax and tumor-to-background ratio were recorded. PET modalities were compared using the McNemar test. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FAPI and SSTR PET were calculated., Results: The cohort comprised 16 patients (50% female; mean age 50 ± 17 years). Median calcitonin and CEA levels were 6234 pg/mL and 17.3 ng/mL, respectively. In patient-based analysis, SSTR exhibited higher diagnostic sensitivity compared with FAPI (88% vs 81%), resulting a statistically significant difference (P = 0.004). Mean SUVmax and tumor-to-background ratio values were 10.3 and 5.35 for FAPI, and 9.7 and 11.9 for SSTR PET, respectively. In lesion-based analyses, FAPI demonstrated higher accuracy than SSTR for cervical LNs (91.9% vs 50%), mediastinal LNs (94.9% vs 54.4%), and liver metastases (57.4% vs 7.3%), respectively. Notably, 31% of patients (n = 5) with FAP-expressing liver lesions showed no uptake on SSTR imaging. MRI confirmed liver metastases in 3 of these patients; however, 2 FAP-expressing lesions were confirmed as hemangiomas. False-positive findings of DOTA primarily included reactive LNs and bone hemangiomas., Conclusions: FAPI PET presents promising outcomes in detecting metastases in recurrent MTC patients. Although its diagnostic performance matches SSTR on a per-patient basis, FAPI PET exhibits superior sensitivity and accuracy in lesion-based analyses, notably for liver and bone metastases., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: This study aims to assess 68 Ga-Trivehexin PET/CT for detecting hyperfunctioning parathyroid tissue in comparison to [ 99m Tc]Tc-MIBI scintigraphy-SPECT/CT (MIBI scan) in patients with primary hyperparathyroidism (PHPT)., Methods: The cohort comprised 13 patients diagnosed with PHPT based on biochemical analyses, including serum calcium, phosphorus, and parathyroid hormone (PTH) levels. Each participant underwent cervical ultrasonography, MIBI scan, and 68 Ga-Trivehexin PET/CT imaging. Complementary 4D-CT and [ 18 F]fluorocholine PET/CT were conducted in 7 patients. Ten lesions of 7 patients underwent PTH wash-out (WO) procedure. 68 Ga-Trivehexin PET/CT findings were compared with other modalities and PTH-WO results., Results: Ten patients had sporadic PHPT, while 3 were diagnosed with MEN-1 syndrome-associated PHPT. One patient did not have any identifiable parathyroid lesion across the imaging modalities. On a patient-based analysis, MIBI scan and 68 Ga-Trivehexin PET/CT identified parathyroid lesions in 10 and 11 patients, respectively. However, 68 Ga-Trivehexin PET/CT detected 7 additional parathyroid lesions that were negative on the MIBI scan. Consequently, 17 lesions were identified and confirmed as hyperfunctioning parathyroid tissue through imaging, PTH-WO, or a combination of both modalities. In lesion-based evaluation, 68 Ga-Trivehexin identified 16 lesions compared to 10 by MIBI scan, resulting in a detection rate of 94.1% and 58.8%, respectively. Notably, in three patients who underwent [ 18 F]fluorocholine PET/CT, no lesions were detected; yet 68 Ga-Trivehexin PET/CT successfully identified parathyroid lesions in two of these patients., Conclusion: Our study provides the first evidence that 68 Ga-Trivehexin PET/CT can effectively identify hyperfunctioning parathyroid tissue with a high detection rate warranting further investigations to comprehensively explore its potential in PHPT management., (© 2024. The Author(s).)

Purpose: The aim of this study was to evaluate the potential role of [ 18 F]FDG positron emission tomography/computed tomography (PET/CT) in the characterization of thymic epithelial tumors (TETs). Materials and Methods: A total of 73 patients who underwent preoperative [ 18 F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUV max ), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI) parameters were analyzed to investigate the prediction of histopathologic grade and advanced stage. Results: The cohort included 26 patients with low-grade thymoma (LGT), 36 patients with high-grade thymoma (HGT), and 11 patients with thymic carcinoma (TC). Ninety-one percent of TC had VTS >2, whereas 31% of LGT and 75% of HGT had VTS >2. SUV max , MTV, and TLG were statistically significantly higher in the TC group than in both thymoma and HGT. Using the cutoff value of 7.25 for SUV max , TC was differentiated from thymomas with 91% sensitivity and 74% specificity. TC had significantly lower HI values than thymomas. HI parameters showed good diagnostic ability to differentiate TC from thymoma and TC from HGT. SUV max , MTV, and TLG were significantly higher in advanced-stage disease than in early-stage disease. Conclusions: Visual and quantitative parameters can reliably predict both advanced disease and the grade of primary tumor in TETs. Therefore, as a promising metabolic imaging method, [ 18 F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice.

Purpose: This study evaluated the effect of an increase in the time interval between hepatic intra-arterial injection of 99m Tc-macroaggregated albumin (MAA) and hepatic artery perfusion scintigraphy (HAPS) on the lung shunt fraction (LSF) and perfused volume (PV) calculations in the treatment planning of selective internal radiation therapy (SIRT). Methods: The authors enrolled 51 HAPS sessions from 40 patients diagnosed with primary or metastatic liver malignancy. All patients underwent scan at the first and fourth hour after hepatic arterial injection of 99m Tc-MAA. Based on single-photon emission computed tomography images, LSF values were measured from each patient's first and fourth hour images. PV1 and PV4 were also calculated based on three-dimensional images using 5% and 10% cutoff threshold values and compared with each other. Results: The authors found that the median of LSF4 was statistically significantly higher than LSF1 (3.05 vs. 4.14, p  ≤ 0.01). There was no statistically significant difference between PV1 and PV4 on the 10% ( p  = 0.72) thresholds. Conclusions: LSF values can be overestimated in case of delayed HAPS, potentially leading to treatment cancellation due to incorrectly high results in patients who could benefit from SIRT. Threshold-based PV values do not significantly change over time; nevertheless, keeping the short interval time would be safer.

Abstract: A 41-year-old woman with newly diagnosed breast cancer had suspicious clinical findings of skin involvement on physical examination. The primary tumor had no FDG uptake in 18 F-FDG PET/CT. Nipple and skin had no pathologic enhancement for invasion in breast MRI. Because the T stage was unclear, the patient underwent 68 Ga-FAPI-04 PET/CT for further evaluation. Combination of 68 Ga-FAPI-04 with dedicated breast PET (MAMMI PET) showed nipple and skin involvement of breast cancer with intense FAPI uptake. Consequently, a skin-sparing mastectomy was performed. Histopathological examination confirmed invasive lobular carcinoma infiltration of the deep dermis in the nipple and skin tissue., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 70-year-old man who was scheduled for surgery because of the recurrence of gastric cancer was referred to our clinic preoperatively. The patient underwent a comprehensive evaluation through 18 F-FDG and 68 Ga-FAPI ( 68 Ga-labeled FAP inhibitors) PET/CT scans. The 68 Ga-FAPI PET/CT scan was particularly valuable in this case because of its ability to detect recurrent mass lesions and identify unusual metastatic sites compared with the 18 F-FDG PET/CT scan., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We aimed to investigate the role of [ 68  Ga]Ga-FAPI-04 PET/CT and uptake patterns of primary and metastatic lesions in patients with renal cell carcinoma (RCC)., Methods: Twenty patients with a suspicious lesion considered primary renal malignancy or a history of RCC were included in our study. Two patients were excluded from further analyses due to other confirmed malignancies. Six patients were newly diagnosed, while the indication of 12 patients was restaging. All patients underwent [ 68  Ga]Ga-FAPI-04 and [ 18 F]F-FDG PET/CT. SUVmax and tumor-to-background ratio (TBR) of primary (n = 7) and local recurrent lesions (n = 6) and lymph node (n = 26), lung (n = 32), bone (n = 5), and other metastases (n = 14) were compared between the two tracers., Results: We detected 90 lesions in 18 patients with varying FAPI and FDG uptake values on both PET/CT. The median TBR of FAPI-PET/CT of all lesions was higher than TBR of FDG-PET/CT with statistically significance (5.6 vs. 2.1, p < 0.001). In primary and recurrent lesions, the median SUVmax, TBR, and tumor volume on FAPI-PET/CT were higher than FDG-PET/CT. The median SUVmax of lung lesions on FAPI-PET/CT was statistical significantly higher than FDG-SUVmax (3.8 vs. 1.8, p = 0.02). The median of FAPI-SUVmax on primary lesions was lower in the early stage based on TNM compared to the advanced stage. FAPI-SUVmax in 49% of all lesions were SUVmax ≥ 6, and 13% were SUVmax ≥ 10. In patient-based analyses, seven patients (39%) had at least one lesion with FAPI-SUVmax ≥ 10; 12 patients (67%) had at least one lesion with FAPI-SUVmax ≥ 6., Conclusion: This study showed the potential utility of [68 Ga]Ga-FAPI-04 PET/CT showing promising results in RCC. We have presumed that FAPI-PET/CT may be performed for complementary imaging modality providing prognosis and possibility of theranostic application in selected patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We aimed to investigate the potential of [ 68 Ga]Ga-FAPI-04 PET/CT as an alternative diagnostic and theranostic tool in well-differentiated NETs refractory to [ 177 Lu]Lu-DOTATATE therapy., Methods: Patients who received at least two cycles of [ 177 Lu]Lu-DOTATATE therapy for metastatic NETs and progressed under treatment were included. All patients had performed [ 68 Ga]Ga-DOTATATE and [ 68 Ga]Ga-FAPI-04 PET/CT within 3 weeks. The number of PET-positive lesions related to NETs and tumor sites was documented. Mann-Whitney U and chi-square tests were used to compare SUVmax levels of tracers and the number of detected metastases., Results: Twelve patients (7 male, 5 female) who met the eligibility criteria were included in the study. Ten patients had grade 1-2 NET of various origins, and two had paraganglioma and pheochromocytoma. One hundred ninety-eight of 230 lesions (86%) were SSTR positive with a median SUVmax of 16.6 (2.2-76.5), and 88 of 230 lesions (38.2%) were [ 68 Ga]Ga-FAPI-04 positive with a median SUVmax of 5.1 (2.3-21). Median SUVmax level and detected number of tumors were significantly higher in [ 68 Ga]Ga-DOTATATE PET/CT (p=<0.001). [ 68 Ga]Ga-FAPI-04 PET/CT was completely (n:2) or almost completely (n:3) negative in 5 (42%) patients. Two (17%) patients had flip-flop SSTR/FAPI uptake in tumors. In four patients (33%), tumor uptake or the number of PET-positive lesions was inferior in [ 68 Ga]Ga-FAPI-04 PET/CT. In only one patient (8%), tumor uptakes were higher in [ 68 Ga]Ga-FAPI-04 PET/CT. Low-dose [ 177 Lu]Lu-FAPI-46 dosimetry was performed on the FAPI-dominant patient; absorbed radiation doses per GBq were 1.26 Gy, 0.36 Gy, 0.32 Gy, and 0.2 Gy for kidneys, liver, spleen, and total body, respectively. The mean absorbed dose per GBq was 0.33 Gy for liver mass and 0.41 Gy for metastatic lymph nodes., Conclusion: Our preliminary results demonstrated that [ 68 Ga]Ga-FAPI-04 PET/CT mainly failed in well-differentiated NETs refractory to [ 177 Lu]Lu-DOTATATE therapy and had a limited role as an alternative diagnostic or theranostic agent. Further investigations with a larger patient population are required to determine the impact of [ 68 Ga]Ga-FAPI-04 PET/CT on NETs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: We present isolated bilateral adrenal metastases successfully treated with 177 Lu-PSMA in a 66-year-old man diagnosed with castration-resistant prostate cancer. The patient had progression under chemotherapy as depicted by 68 Ga-PSMA PET/CT showing intense bilateral PSMA uptake in the adrenal masses, and metastasis-directed therapies were considered as the first option for improving survival because the patient was oligometastatic. However, surgery and radiotherapy were not justifiable options due to the high risk of definitive adrenal insufficiency; therefore, the patient received 4 cycles of 177 Lu-PSMA treatment. 68 Ga-PSMA PET/CT showed near-complete response in bilateral adrenal metastases, and no sign of adrenal insufficiency was observed during follow-up., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 69-year-old woman with breast cancer underwent 18 F-FDG PET/CT because of the increased CA-15-3 level. 18 F-FDG PET/CT showed multiple hypermetabolic lymph nodes (LNs) in the neck and mediastinum. The patient was also referred for 68 Ga-fibroblast activation protein inhibitor (FAPI) 04 PET/CT for further evaluation. However, 18 F-FDG-avid LNs were FAPI-negative on 68 Ga-FAPI-04 PET/CT. Supraclavicular LN biopsy confirmed the metastasis of breast cancer. Recent reports have focused on the potential of FAPI PET imaging in breast cancer; however, this case highlights that false-negative 68 Ga-FAPI-04-PET/CT findings should also be considered while evaluating metastatic spread., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT is an emerging imaging modality with high sensitivity and high tumor-to-background ratio in various cancers including in the head and neck regions. The authors present 2 cases of adenoid cystic carcinoma who underwent 68 Ga-FAPI-04 and 18 F-FDG PET/CT. Locoregional recurrence has been detected more precisely in the first case with 68 Ga-FAPI-04. In the second case, 68 Ga-FAPI-04 outperformed 18 F-FDG in the number of lesions and demonstrated intense FAP uptake on widespread metastases, which could provide a treatment option as a theranostic concept. These cases highlight that 68 Ga-FAPI-04 PET/CT may be useful for detecting local recurrence and metastases and help select patients for radionuclide treatments targeting cancer-associated fibroblasts., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 60-year-old woman diagnosed with clear cell endometrial carcinoma received neoadjuvant chemotherapy. However, the patient was inoperable and referred to our clinic to evaluate the extent of the disease. The patient underwent 18FDG PET/CT and 68Ga-FAPI (fibroblast activated protein inhibitor)-04 PET/CT scans. 68Ga-FAPI-04 PET/CT outperformed 18FDG PET/CT demonstrating higher uptake in the metastatic lesions., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We assessed the feasibility of SPECT/CT lymphoscintigraphy ( 99m Tc-nanocolloid) method to simplify and improve targeted axillary dissection of clipped axillary lymph node (axLN) after neoadjuvant chemotherapy (NAC) in initially node-positive breast cancer., Patients and Methods: Fifteen patients who had clip placement to biopsy-confirmed axLN metastasis due to clinically node-positive breast cancer before NAC and underwent SPECT/CT lymphoscintigraphy for surgery after NAC were included into the study. SPECT/CT lymphoscintigraphy was performed to localize the clipped node and to assess if the clipped lymph node (LN) had 99m Tc-nanocolloid uptake or not. In case the clipped node had no uptake on SPECT/CT, the patient was referred to wire-guided localization procedure. Blue dye was also injected for dual mapping of sentinel LN biopsy., Results: All patients had only ipsilateral axLN metastasis. SPECT/CT lymphoscintigraphy showed that clipped LNs were radioavid in 12 of 15 patients (80%). Clipped LNs were not blue-stained in 5 patients (33.3%), and in 2 of them, clipped LNs were radioavid in SPECT/CT. Wire-guided localization was required in only 3 patients (20%) for nonradioavid/blue-stained clipped LNs. Removal of the clipped nodes was confirmed in all cases with a success rate of 100% by specimen graphy., Conclusion: SPECT/CT lymphoscintigraphy seems feasible to determine the clipped LNs intraoperatively without requiring additional invasive methods in most of the patients. This technique simplifies and improves targeted axillary dissection of the clipped axLNs after NAC in initially node-positive breast cancer and can be adapted to clinical practice with further investigations., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study was set out to analyze the efficacy and safety of 177 Lu-PSMA-617 (LuPSMA) treatment in metastatic castration-resistant prostate cancer (mCRPC) patients., Patients and Methods: Progressive mCRPC patients who received at least 1 cycle of LuPSMA therapy were evaluated retrospectively. Demographic, clinic, and histopathological data were documented. Treatment efficacy was determined based on biochemical response criteria (Prostate Cancer Clinical Trial Working Group 3), and toxicity rates were defined based on CTCAE v4.03. The prognostic significance of laboratory/clinical data and 68 Ga-PSMA PET/CT quantitative results were analyzed using SPSS Version 24.0., Results: One hundred patients (median prostate-specific antigen [PSA] level, 75.7 ng/mL) who met the eligibility criteria were identified. The median number of cycles received per patient was 3 (range, 1-9). After the first cycles of LuPSMA, biochemical partial response, biochemical stable disease, and biochemical progressive disease were observed in 31%, 36%, and 33% of patients, respectively. Any PSA decline was determined in 60% of patients. After the fourth cycle of treatment, biochemical partial response, biochemical stable disease, and biochemical progressive disease were defined in 48%, 26%, and 26% of patients, respectively. The median overall survival (OS) from the first cycle of LuPSMA was 14 months. Patients who had any PSA response after the first cycle had significantly longer OS than nonresponders (median OS: 17 vs 9 months; P ≤ 0.001). Total PSMA-derived tumor volume ( P = 0.004), total PSMA activity per lesion ( P = 0.01), PSA ( P = 0.007), alkaline phosphatase ( P = 0.002), lactate dehydrogenase ( P < 0.001), and hemoglobin ( P < 0.001) were significant prognostic factors for OS in univariate Cox regression analysis., Conclusions: LuPSMA therapy is a favorable treatment for mCRPC with remarkable therapeutic efficacy and low toxicity rates, even in progressive disease under standard therapies. Baseline PSMA-based tumor burden, PSA, alkaline phosphatase, lactate dehydrogenase, and hemoglobin were significant predictors of OS and can be useful for selection of the best candidate for LuPSMA therapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Split renal function (SRF) can be measured by using several methods in 99m Tc-DMSA scintigraphy. Geometric mean (GM) based methods derived from planar images(2D) have been used for several years, besides; 3D-methods were also reported as an option for assessment of SRF. The purpose of this study to compare 2D and 3D methods for calculation of SRF in pediatric and adult patients., Methods: We evaluated 212 patients, underwent both planar and SPECT 99m Tc-DMSA scintigraphy.2D-SRFs were calculated by GM without background correction (SRFnobcg), GM with background correction in crescent formation from lower lateral borders (SRFcres), and GM with background correction in circumferential formation, including the whole kidney surroundings (SRFcirc). In 3D settings, SRF was measured with SPECT (SRFspect). Paired t-test was used to compare the mean SRFs of each group. Bland-Altman method was used as an agreement method for each method. Analyses were performed based on left kidney SRFs., Results: In comparison of 2D and 3D methods, SRFspect was significantly different from SRFnobcg and SRFcres (p=<0.001) but not from SRFcirc (p = 0.155) in all patients. Similar results were found for patients with high creatinine level, SRFcirc and SRFspect were not significantly different (p = 0.317), while significant differences were found between SRFspect and SRFnobcg/SRFcres (p=<0.001).On the other hand, all 2D-methods showed statistical differences (p=<0.001-0.026) from 3D-method in pediatric patients. Bland-Altman-plot demonstrated that SRFcirc underestimated the poor functioning kidneys., Conclusion: SRFcirc can be used in measurement of SRF in adult patients with normal functioning kidneys in busy clinics. However, SRFspect provides more accurate results and suggested particularly for pediatric patients and poor functioning kidneys., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Abstract: We present the case of a 48-year-old man diagnosed with metastatic Ewing sarcoma who was referred for 18F-FDG PET/CT for treatment response evaluation following chemoradiotherapy. The patient also had complaints of new-onset testicular swelling at the time of imaging. Although the metastatic bone disease showed a complete metabolic response to treatment, 18F-FDG PET/CT demonstrated significantly increased metabolic activity in bilateral testicular mass. Consequently, the patient underwent bilateral orchiectomy, and histopathologic examination revealed bilateral testicular plasmacytoma, a rare manifestation of extramedullary plasmacytoma., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Herein we present 2 mCRPC (metastatic castration-resistant prostate cancer) patients who underwent 68Ga-PSMA PET/CT for PSMA-targeted radioligand therapy eligibility. Prior studies have noted aggressive clinical behavior and poor prognosis associated with discordant FDG positivity and low PSMA expression. Accordingly, the patients also underwent 18F-FDG PET/CT, which revealed intratumoral heterogeneity. Therefore, an additional PET/CT targeting fibroblast activation proteins (FAPs) using 68Ga-FAPI-04 was performed to assess the potential for an FAP-targeted therapy. This report highlights the theranostic potential of FAP imaging in mCRPC, particularly in patients with heterogeneous tumor phenotypes., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Herein, we present a 72-year-old woman with metastatic thymic carcinoma, referred for salvage peptide receptor radionuclide therapy with 177Lu-DOTATATE after completing all treatment options according to current clinical practice and guidelines. However, the patient was not eligible for 177Lu-DOTATATE peptide receptor radionuclide therapy and underwent 68Ga-FAPI04 PET/CT to assess the potential for a FAP-targeted therapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study investigates the prognostic value of 68 Ga-Pentixafor PET/CT using PET-derived quantitative in multiple myeloma (MM) patients with suspected recurrence in comparison to 18 F-FDG PET/CT and clinical data., Methods: Twenty-four MM patients with suspicion for relapse who underwent 68 Ga-Pentixafor and 18 F-FDG PET/CT were retrospectively evaluated. Total bone marrow glycolysis for 18 F-FDG (TBM FDG ) and total bone marrow uptake for 68 Ga-Pentixafor PET/CT (TBM CXCR4 ) were calculated using whole-body metabolic tumor burden obtained by dedicated software (MIM 7.0.6). The patients were followed for 19-24 months, and the association of PET-derived quantitative data with overall survival (OS) was analyzed., Results: 68 Ga-Pentixafor PET/CT was positive in 17 patients, of which 13 were also positive on 18 F-FDG PET/CT, whereas 7 patients were negative on both scans. The positive rate of 68 Ga-Pentixafor and 18 F-FDG PET/CT on a patient-based approach was 70.8% and 54.1%, respectively. 68 Ga-Pentixafor positivity was significantly associated with OS (p = 0.009), and 18 F-FDG positivity was at the margin of statistical significance (p = 0.056). TBM CXCR4 and TBM FDG were negatively correlated with OS (r = -0.457, p = 0.025 and r = -0.617, p = 0.001, respectively). The OS was negatively correlated with beta-2-microglobulin levels (r = -0.511, p = 0.01) and CRAB score (r = -0.592, p = 0.002) as an indicator of the end-organ disease, which confirmed these results. Serum beta-2-microglobulin levels and CRAB score were also correlated with TBM CXCR4 (r = 0.442, p = 0.039 and r = 0.573, p = 0.003, respectively) and TBM FDG (r = 0.543, p = 0.009 and r = -0.424, p = 0.003, respectively)., Conclusion: 68 Ga-Pentixafor PET/CT positivity is a negative prognostic factor in the survival outcome of MM patients. Complementary 68 Ga-Pentixafor PET/CT has the potential to overcome 18 F-FDG PET/CT limitations and helps a more precise risk stratification., (© 2021. The Japanese Society of Nuclear Medicine.)

Objectives: This study is set out to estimate the radiation-absorbed doses to normal organs and tumor tissue using low-dose 177Lu-FAPI04 dosimetry to determine the safety and theranostic potential of fibroblast activation protein-targeted radionuclide therapy., Patients and Methods: Four patients with metastatic advanced-stage cancer were administered low-dose 177Lu-FAPI04 for dosimetry measurements. Data acquisition for dosimetry of normal organs and tumors was performed by whole-body and 3D SPECT/CT imaging at 4, 24, 48, and 96 hours after administering 177Lu-FAPI04. Blood samples were drawn at 5, 15, 30, 60, 60, 120, and 180 minutes, and at 24, 48, and 96 hours for bone marrow dosimetry calculations., Results: Mean absorbed doses per megabecquerel were 0.25 ± 0.16 mGy (range, 0.11-0.47 mGy), 0.11 ± 0.08 mGy (range, 0.06-0.22 mGy), and 0.04 ± 0.002 mGy (range, 0.04-0.046 mGy) for kidneys, liver, and bone marrow, respectively. The respective maximum estimated amount of radioactivity to reach radiation-absorbed dose limits were 120.9 ± 68.6 GBq, 47.5 ± 2.8 GBq, 397.8 ± 217.1 GBq, and 52.4 ± 15.3 GBq for kidneys, bone marrow, liver, and total body. The mean absorbed dose per megabecquerel was 0.62 ± 0.55 mGy for bone metastases, 0.38 ± 0.22 mGy for metastatic lymph nodes, 0.33 ± 0.21 mGy for liver metastases, and 0.37 ± 0.29 for metastatic soft tissue. The maximum absorbed dose in a tumor lesion was 1.67 mGy/MBq for bone, 0.6 mGy/MBq for lymph node, 0.62 mGy/MBq for liver, and 1 mGy/MBq for soft tissue., Conclusions: The mean absorbed dose to organs at risk with 177Lu-FAPI04 is reasonably low, allowing for low tumor-absorbed dose rates by administering a higher dose. Further research on optimizing therapeutic efficacy and using alternative radioisotopes is necessary, along with an individualized dosimetric approach., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Somatostatin receptor (SSTR) imaging with 68Ga-labeled somatostatin analogs has been used for many tumors with high SSTR expression. Increased uptake mostly depends on the SSTR status of tumors; however, false-positive uptake can be demonstrated in benign diseases or other malignancies because of the increased SSTR expression. We present a case of a 50-year-old man with increased SSTR activity on cervical lesion located in internal jugular chain in 68Ga-DOTATATE PET/CT, which was performed for suspicion of paraganglioma. Biopsy revealed lymph node metastasis of squamous cell carcinoma other than paraganglioma. 18F-FDG PET/CT showed primary malignancy on larynx and lymph node metastasis, which were correlated surgically., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: We present a case of clear cell renal cell carcinoma, which demonstrates complementary FDG and prostate-specific membrane antigen (PSMA) uptake on metastases in PET/CT, as an example of tumor heterogeneity. The patient had non-FDG-avid lung and bone metastases with PSMA uptake, whereas metastatic cervical and axillary lymph nodes showed vice versa, and skeletal muscle metastasis to vastus lateralis, which is an unusual region for metastasis, showed both PSMA and FDG positivity. In response assessment, mix response was detected. It seems that 68Ga-PSMA and 18F-FDG may have a complementary role in demonstration of metastasis accurately and assessment of treatment response in clear cell renal cell carcinoma., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We investigated the role of PSMA-derived tumor burden in predicting docetaxel (DTX) therapy response in metastatic castration-resistant prostate cancer (mCRPC)., Methods: Fifty-two mCRPC patients who received at least six cycles of DTX as the first-line treatment following 68 Ga-PSMA PET/CT were enrolled in this retrospective study. Total PSMA-derived tumor volume (TV-PSMA) and total lesion PSMA activity (TL-PSMA) were derived from metastatic lesions. A ≥ 50% decline in PSA was defined as a response; a ≥ 25% increase in PSA was defined as progression. Univariate/multivariate logistic and cox regression analyses were performed to predict PSA response, OS, and TTP., Results: Twelve (23%) patients had PSA progression after chemotherapy, while 40 patients (77%) achieved a PSA response. On univariate analysis, a significant association was found between TV-PSMA (p = 0.001), TL-PSMA (p = 0.001), pre-PSA (p = 0.012), LDH (p = 0.003), Hg (p = 0.035), and PSA response to DTX. High TV-PSMA (> 107 cm 3 ) (p = 0.04) and high LDH (> 234 U/L) (p = 0.017) were 8.2 times and 12.2 times more likely for DTX failure in multivariate regression analyses. The median TTP was 16 months, and the median OS was not reached. Patients with high TV-PSMA (p = 0.017), high TL-PSMA (> 1013 cm 3 ) (p = 0.042), high age (> 70 years) (p = 0.016), and high LDH (p ≤ 0.001) had significantly shorter OS, while only high TV-PSMA (p = 0.038) and high age (p = 0.006) were significantly related with shorter TTP. High TV-PSMA (p = 0.017) and high age (p = 0.01) were significant predictors for shorter OS, while only high age (p = 0.006) was a significant predictor for shorter TTP in multivariate analysis., Conclusion: Patients with high TV-PSMA had a significantly higher risk for DTX failure. PSMA-based tumor burden prior to DTX therapy seems to be a reliable predictive tool for survival in mCRPC patients.

Abstract: Prostate-specific membrane antigen (PSMA) overexpression in various tumors are demonstrated in both in vitro and in vivo studies. Prostate-specific membrane antigen-directed radionuclide therapies are generally used in prostate cancer and could be also useful in PSMA-avid other malignancies. Herein, we present a case of a 46-year-old male patient who had progressive metastatic testicular mixed germ cell tumor, despite repeated operations and treatments. 68Ga-PSMA PET/CT was performed to assess eligibility for 177Lu-PSMA therapy. Patient had intense PSMA uptake in metastatic lesions, and 177Lu-PSMA has been given to control of disease. However, α-fetoprotein level progressed, and mixed therapy response was detected in 68Ga-PSMA PET/CT., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study sets out to evaluate patients with increased uptake in breast lesions on 68 Ga-DOTATATE PET/CT (DOTA PET) and determine the clinical significance of somatostatin receptor (SSTR) positive breast lesions., Methods: We retrospectively evaluated all patients with increased SSTR uptake in breast lesions on DOTA PET. Patients with physiological (e.g., lactation) or normal variant breast uptake (e.g., mild diffuse glandular uptake) were excluded. The maximum standard uptake value (SUVmax) was calculated using a manually drawn region of interest in the most intense uptake of breast lesions. All lesions were correlated with breast imaging, including mammography and ultrasonography. Histopathological correlation was performed if the lesion was suspicious for malignancy. Lesions were followed up radiologically (1-8 years)., Results: Out of 1573 retrospectively analyzed DOTA PET scans, the incidence of SSTR + breast lesions was measured as 1.1% (n = 18); however, 4 of 18 patients were excluded due to the lack of final diagnosis of lesions. The median age was 35 (range 14-58 years), and all patients were female. The median SUVmax of SSTR + breast lesions was 5.2 (range 1.5-12.6) for a total of 14 patients. Twelve patients had a single SSTR + breast lesion, while 2 patients had multiple SSTR + lesions on bilateral breasts. In 6 patients, single SSTR + lesions were considered as fibroadenoma; in 2 patients, multiple SSTR + lesions were considered as metastases of NET, based on correlative breast imaging. In 6 patients, histopathological confirmation was needed for the final diagnosis. Histopathologic findings confirmed fibroadenoma in 4 patients by biopsy, in 1 patient with surgical removal of the lesion. The last patient who had a history of IDC was diagnosed with a recurrence of IDC with biopsy. The median SUVmax was 5.1 (range 1.5-9.4) for malignant breast lesions and 5.4 (range 2.2-12.6) for benign breast lesions., Conclusion: SSTR + breast lesions on DOTA PET are rarely seen in clinical practice. Uptakes of breast lesions in our cases were variable and not useful for differential diagnosis of lesions. It seems that SSTR + breast lesions should be evaluated with clinical and radiological characteristics, and correlative breast imaging and/or histopathological verification should be performed for suspicious lesions to avoid misdiagnosis.

In vivo prostate-specific membrane antigen (PSMA) overexpression creates an opportunity for PSMA-directed theranostic approach in adenoid cystic carcinoma of the parotid. Herein, we illustrate a patient with metastatic PSMA-directed theranostic approach in adenoid cystic carcinoma of the parotid who had intense PSMA uptake on metastatic lesions, followed by radionuclide therapy with Lu-PSMA.

Prostate specific membrane antigen (PSMA) expression has been demonstrated in tumor neovasculature of many solid tumors, including hepatocellular carcinoma (HCC). The purpose of this study is to evaluate PSMA expression in patients with HCC., Materials and Methods: Nineteen HCC patients who underwent F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) as part of restaging procedure also underwent Ga-PSMA PET. F-FDG PET and Ga-PSMA findings were compared visually as well as quantitatively using maximized standardized uptake values (SUVmax)., Results: FDG was positive in 15 patients while 16 patients demonstrated PSMA expression. The only extrahepatic finding was one metastatic lymph node detected by both tracers. Mean SUVmax of liver lesions on FDG PET/CT was 8.3 ± 2.3 and mean tumor to background ratio was 2.3 ± 1.5. Respective values for Ga-PSMA PET/CT were 17.4 ± 9 and 3.3 ± 2.2. On visual and quantitative evaluation uptake was higher with PSMA in nine patients and higher with FDG in four patients. PSMA and FDG activity were similar in three patients. One of the FDG positive patients was PSMA negative whereas two patients were PSMA positive but FDG negative. Heterogeneous uptake pattern was observed in three patients. Comparison of mean SUVmax and T/B values between PET studies revealed no statistically significant difference (P > 0.1). The mean survival was 25 months (range: 18-32 months) and SUVmax of PSMA (P = 0.05) and FDG (P = 0.012) showed medium strength of correlation with overall survival., Conclusion: PSMA expression in advanced HCC can be demonstrated by Ga-PSMA PET but is not superior to FDG PET however it could be useful for identifying patients with limited therapeutic options.

Treatment of high-risk prostate cancer (HRPCa) is challenging. Local staging and metastatic evaluation are important for the patient management. Recently, prostate-specific membrane antigen (PSMA)-based imaging modalities such as PSMA PET/CT and PET/MRI have received significant attention for detection of recurrent prostate cancer sites with elevated prostate-specific antigen levels, after therapy. Current evidence suggests that these imaging modalities may also have a role for the management of patients with HRPCa. In this review, we discuss PSMA-based imaging modalities in the management of patients with HRPCa.

Ga-prostate-specific membrane antigen (PSMA) PET/CT is a rapidly evolving diagnostic technique to image prostate cancer. In contrast to the name PSMA, various tissues show Ga-PSMA uptake in PET/CT imaging. We present a case of a 68-year-old man with prostate cancer who underwent Ga-PSMA PET/CT. Along with metastatic lymph nodes, multiple nodular lesions within the peritoneal spaces of all 4 quadrants of the abdomen showed high PSMA expression. Because of a history of splenic rupture, a Tc-labeled heat-denatured erythrocyte scintigraphy and SPECT were performed. Peritoneal lesions showed high uptake, confirming widespread peritoneal splenosis.

Unlabelled: Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are indolent neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. Tumor size, existence of metastasis, and histopathologic classification remain incapable in terms of treatment decision and prognosis estimation. This study aimed to compare (68)Ga-DOTATATE and (18)F-FDG PET/CT in GEPNETs and to investigate the relation between the complementary PET/CT results and histopathologic findings in the management of therapy, particularly in intermediate-grade patients., Methods: The relation between complementary (68)Ga-DOTATATE and (18)F-FDG PET/CT results of 27 GEPNET patients (mean age, 56 y; age range, 33-79 y) and histopathologic findings was evaluated according to grade and localization using standardized maximum uptake values and Ki67 indices. Grade 2 (G2) patients were further evaluated in 2 groups as G2a (3%-9%) and G2b (10%-20%) according to Ki67 indices., Results: The sensitivity of (68)Ga-DOTATATE and (18)F-FDG PET/CT was 95% and 37%, respectively, and the positive predictive values were 93.8% and 36.2%, respectively. The sensitivity in detecting liver metastasis, lymph nodes, bone metastasis, and primary lesion was 95%, 95%, 90%, and 93% for (68)Ga-DOTATATE and 40%, 28%, 28%, and 75% for (18)F-FDG, respectively. Statistically significant differences were found between grades 1-2, 2a-2b, and 1-2b with respect to (68)Ga-DOTATATE PET/CT as well as between 1-2a and 1-2b with respect to (18)F-FDG PET/CT. However, no statistical differences were found between 1 and 2a (P > 0.05) for (68)Ga-DOTATATE and 2a and 2b (P = 0.484) for (18)F-FDG. The impact of the combined (18)F-FDG and (68)Ga-DOTATATE PET/CT on the therapeutic decision was 59%., Conclusion: Combined (68)Ga-DOTATATE and (18)F-FDG PET/CT is helpful in the individual therapeutic approach of GEPNETs and can overcome the shortcomings of histopathologic grading especially in intermediate-grade GEPNETs., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)