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.

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.

Neuroendocrine Tumor Diagnosis and Management: 68Ga-DOTATATE PET/CT.

OBJECTIVE: The purpose of this article is to provide a review of the use of 68Ga tetraazacyclododecanetetraacetic acid-DPhe1-Tyr3-octreotate (DOTATATE) PET/CT, a functional imaging modality for assessment of well-differentiated neuroendocrine tumors (NETs). It has become the preferred imaging modality for initial diagnosis, selection of patients for peptide receptor radionuclide therapy, and localization of unknown primary tumors. The National Comprehensive Cancer Network guideline has added 68Ga-DOTATATE PET/CT as an appropriate test in the management of NETs. CONCLUSION: In combination with FDG PET/CT, 68Ga-DOTATATE PET/CT can noninvasively assess tumor heterogeneity, especially in G2 and G3 NETs, for personalized management of 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.

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.

68 Ga-FAPI04 Versus 68 Ga-DOTATATE PET/CT in a Patient With Multiple Meningioma.

ABSTRACT: We present the 68 Ga-DOTATATE and 68 Ga-FAPI (fibroblast activation protein inhibitor) PET/CT findings of a 61-year-old man diagnosed with atypical World Health Organization grade II multiple meningiomas. The patient has been stable for 2 years following multiple surgeries and external radiotherapy because of recurring disease until he recently described frequent headaches, and a follow-up examination confirmed new meningioma lesions on MRI. However, the patient was inoperable and was referred for 68 Ga-DOTATATE PET/CT to determine eligibility for salvage peptide receptor radionuclide therapy. He also underwent fibroblast activation protein-targeted imaging using 68 Ga-FAPI04 PET/CT, which revealed heterogeneous, low to mild fibroblast activation protein expression across multiple meningioma lesions.

68 Ga-FAPI-04 PET/CT and 18 F-FDG PET/CT in Metastatic Papillary Renal Cell Cancer.

ABSTRACT: Papillary renal cell cancer is a rare malignancy with limited treatment options in the advanced stage of the disease. We present the case of a 62-year-old man with progressive left-sided papillary renal cell carcinoma who underwent 68 Ga-FAPI (fibroblast activated protein inhibitor)-04 and 18 F-FDG PET/CT imaging. 68 Ga-FAPI-04 PET/CT demonstrated variable FAP expression in all metastatic lesions detected by 18 F-FDG PET/CT, including multiple lymph nodes, bone, and thyroid. This case highlights that FAP-targeted imaging can be a promising modality for diagnostic and theranostic use in papillary renal cell carcinoma.

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.

Role of red blood cell scintigraphy for determining the localization of gastrointestinal bleeding.

BACKGROUND: We aimed to evaluate the role of Tc-99m labeled red blood cell (RBC) scintigraphy for determination of localization of gastrointestinal system (GIS) bleeding. METHODS: Fifty-seven cases (27 females, 30 males; mean age 43.9±24; range 1 to 91 years) who referred to our clinic between 1995-2010 were evaluated for determination of localization of GIS bleeding with RBC scintigraphy. Prior to scintigraphy, gastroscopy in 51, colonoscopy in 45, and angiography in 9 patients were performed. RESULTS: RBC scintigraphies were positive and negative in 31 and 26 patients, respectively. Positive scintigraphic findings were obtained within the 1st hour of dynamic imaging in 19 patients, within the 1st-4th hour static images in 7, and within the 4th-24th hour images in 5 patients. Fourteen patients underwent surgical exploration. In 13 patients, the surgery confirmed the diagnosis by RBC scintigraphy (accuracy: 92.8%). Of 43 patients without surgical exploration, 12 had anemia due to iron deficiency and their scintigraphic evaluation were negative. Four patients died and in 27 patients, GIS bleeding ceased spontaneously or with conservative measures. CONCLUSION: Scintigraphy should be the primary tool for accurate diagnosis of patients with active GIS bleeding. Positive dynamic images obtained within the first hour of imaging may be more accurate for demonstrating bleeding localization and a good predictor of requirement of surgical exploration.

68Ga-PSMA Uptake Patterns of Clear Cell Renal Carcinoma Across Different Histopathological Subtypes.

ABSTRACT: 68Ga-prostate-specific membrane antigen (PSMA) PET/CT is a well-established imaging modality in patients with prostate cancer; however, PSMA expression is also reported in the tumor-associated neovasculature, including but not limited to hepatocellular carcinoma, breast cancer, and renal cell carcinoma. Herein, we present 2 patients diagnosed with different histopathological subtypes of renal cell carcinoma who underwent 68Ga-PSMA PET/CT before surgery. Both cases have different PSMA expression characteristics and are presented along with pathological findings.

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.