68Ga-Trivehexin PET/CT: a promising novel tracer for primary hyperparathyroidism.

INTRODUCTION: This study aims to assess 68Ga-Trivehexin PET/CT for detecting hyperfunctioning parathyroid tissue in comparison to [99mTc]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 68Ga-Trivehexin PET/CT imaging. Complementary 4D-CT and [18F]fluorocholine PET/CT were conducted in 7 patients. Ten lesions of 7 patients underwent PTH wash-out (WO) procedure. 68Ga-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 68Ga-Trivehexin PET/CT identified parathyroid lesions in 10 and 11 patients, respectively. However, 68Ga-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, 68Ga-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 [18F]fluorocholine PET/CT, no lesions were detected; yet 68Ga-Trivehexin PET/CT successfully identified parathyroid lesions in two of these patients. CONCLUSION: Our study provides the first evidence that 68Ga-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.

The inferior performance of [68Ga]Ga-FAPI-04 PET/CT as a diagnostic and theranostic biomarker in [177Lu]Lu-DOTATATE refractory well-differentiated neuroendocrine tumors.

PURPOSE: We aimed to investigate the potential of [68Ga]Ga-FAPI-04 PET/CT as an alternative diagnostic and theranostic tool in well-differentiated NETs refractory to [177Lu]Lu-DOTATATE therapy. METHODS: Patients who received at least two cycles of [177Lu]Lu-DOTATATE therapy for metastatic NETs and progressed under treatment were included. All patients had performed [68Ga]Ga-DOTATATE and [68Ga]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 [68Ga]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 [68Ga]Ga-DOTATATE PET/CT (p=<0.001). [68Ga]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 [68Ga]Ga-FAPI-04 PET/CT. In only one patient (8%), tumor uptakes were higher in [68Ga]Ga-FAPI-04 PET/CT. Low-dose [177Lu]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 [68Ga]Ga-FAPI-04 PET/CT mainly failed in well-differentiated NETs refractory to [177Lu]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 [68Ga]Ga-FAPI-04 PET/CT on NETs.

The role of [68 Ga]Ga-FAPI-04 PET/CT in renal cell carcinoma: a preliminary study.

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 [18F]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.

Diagnosis and Evaluation of Treatment Response in Relapsing Polychondritis Using 18F-FDG PET/CT.

A 58-year-old man presenting with dyspnea, weight loss, and night sweating underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) because of a suspicion of malignancy. 18F-FDG PET/CT demonstrated mild to moderate uptake on nasal, cricoid, and tracheobronchial tree cartilages and costovertebral junctions. The diagnosis was relapsing polychondritis, which is a rare multisystem disease characterized by inflammation of cartilage. In addition, subsequent 18F-FDG PET/CT after treatment showed complete metabolic response.

18F-FDG and 68Ga-FAPI-04 PET/CT Findings of a Rare Epithelial-myoepithelial Carcinoma Arising From Ex Pleomorphic Adenoma of Parotid.

Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland neoplasm. Distant metastasis is rare, and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been used to determine the metastatic disease in EMC. 68Ga-fibroblast activation protein inhibitors (FAPI) PET/CT is a promising imaging modality for diagnostic and theognostic purposes in various malignancies. Comparison studies with 18F-FDG have investigated the role of 68Ga-FAPI PET/CT. Herein, we present 18F-FDG and 68Ga-FAPI-04 PET/CT findings of a 51-year-old woman with metastatic EMC arising from ex-pleomorphic adenoma of the parotid.

Combination of 68 Ga-FAPI-04 and Dedicated Breast PET (MAMMI PET) Outperformed Breast MRI and 18 F-FDG PET/CT by Revealing Nipple and Skin Involvement of Breast Cancer.

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.

Isolated Adrenal Metastases of Castration-Resistant Prostate Cancer: Excellent Response to 177 Lu-PSMA With No Adrenal Insufficiency.

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.

Unusual Metastasis of Signet-Ring Cell Gastric Cancer That Could Not Be Detected With 18 F-FDG PET But With 68 Ga-FAPI PET/CT.

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.

Influence of Early Versus Delayed Hepatic Artery Perfusion Scan on 90Y Selective Internal Radiation Therapy Planning.

Purpose: This study evaluated the effect of an increase in the time interval between hepatic intra-arterial injection of 99mTc-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 99mTc-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.

The Role of [18F]FDG PET/CT in the Characterization of Thymic Epithelial Tumors at Initial Stage.

Purpose: The aim of this study was to evaluate the potential role of [18F]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 [18F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUVmax), 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. SUVmax, 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 SUVmax, 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. SUVmax, 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, [18F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice.

18F-FDG and 68Ga-FAPI-04 PET/CT in Evaluating Clear-Cell Endometrial Cancer.

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.

FAPI-Negative FDG-Avid Metastatic Relapse of Breast Cancer on PET/CT.

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.

Utility of 68 Ga-FAPI-04 PET/CT in Adenoid Cystic Carcinoma Compared With 18 F-FDG PET/CT : Two Case Reports.

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.

An anthropomorphic body phantom for the determination of calibration factor in radionuclide treatment dosimetry.

The aim of this study is to create an inhomogeneous human-like phantom, whose attenuation and scattering effects are similar to the human body, as an alternative to the homogeneous phantoms traditionally used in calibration factor (CF) determination. The phantom was designed to include the thorax, abdomen and upper pelvis regions sized to represent a 75-kg male with a body mass index of 25. Measurements using Lu-177 with 50- and 100-mL lesion volumes were performed using inhomogeneous anthropomorphic body phantom (ABP) and homogeneous NEMA PET body phantom. There was a difference of 5.7% of Calibration Factor including attenuation and scatter effect between ABP and NEMA PET body phantom. Because it better reflects the attenuation and scatter effect, it is recommended to use a human-like inhomogeneous phantom for determination of CF instead of a homogeneous phantom.

Fibroblast Activation Protein-Targeted PET Imaging of Metastatic Castration-Resistant Prostate Cancer Compared With 68Ga-PSMA and 18F-FDG PET/CT.

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.

Bilateral Testicular Mass Presenting as a Rare Manifestation of Extramedullary Plasmacytoma on 18F-FDG PET/CT.

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.

Intratumoral Heterogeneity in a Patient With Metastatic Thymic Carcinoma on 18F-FDG, 68Ga-DOTATATE, and 68Ga-FAPI04 PET/CT.

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.

Outcome of 177 Lu-PSMA Radionuclide Treatment in Advanced Prostate Cancer and Its Association With Clinical Parameters : A Single-Center Experience.

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.