Interesting Findings in 68 Ga-FAPI-46 PET/CT Imaging in a Patient With Glioblastoma Multiforme.

ABSTRACT: A 55-year-old disabled man with glioblastoma multiforme was referred to us for fibroblast activation protein inhibitor (FAPI) PET/CT imaging. 68 Ga-DOTA-FAPI-46 scan revealed uptake in the primary tumor and unexpected uptakes in soft tissue, especially in periarticular regions. These latter foci were compatible with calcifications on the CT. One in the breast was compatible with fibrotic tissue, but 2 other foci, in the rectus abdominis and gallbladder wall, could not be correlated with the CT findings. In Neurogenic heterotopic ossification, hypoxia-associated oxidative stress results in the metaplastic transformation of fibroblasts. Abnormal differentiation of fibroblasts in neurogenic heterotopic ossification before ossification could explain radiolabeled FAPI avidity in the mentioned areas.

The value of FDG PET/CT imaging in outcome prediction and response assessment of lymphoma patients treated with immunotherapy: a meta-analysis and systematic review.

PURPOSE: Treatment strategies of lymphoid malignancies have been revolutionized by immunotherapy. Because of the inherent property of Hodgkin lymphoma and some subtypes of non-Hodgkin lymphoma as a highly FDG-avid tumor, functional 18F-FDG PET/CT imaging is already embedded in their routine care. Nevertheless, the question is whether it is still valuable in the context of these tumors being treated with immunotherapy. Herein, we will review the value of 18F-FDG PET/CT imaging lymphoid tumors treated with immunotherapy regimens. METHODS: A comprehensive literature search of the PubMed database was conducted on the value of the 18F-FDG PET/CT for immunotherapy response monitoring of patients with malignant lymphoma. The articles were considered eligible if they met all of the following inclusion criteria: (a) clinical studies on patients with different types of malignant lymphoma, (b) treatment with anti-CD20 antibodies, immune checkpoint inhibitors or immune cell therapies, (c) and incorporated PET/CT with 18F-FDG as the PET tracer. RESULTS: From the initial 1488 papers identified, 91 were ultimately included in our study. In anti-CD20 therapy, the highest pooled hazard ratios (HRs) of baseline, early, and late response monitoring parameters for progression-free survival (PFS) belong to metabolic tumor volume (MTV) (3.19 (95%CI: 2.36-4.30)), maximum standardized uptake value (SUVmax) (3.25 (95%CI: 2.08-5.08)), and Deauville score (DS) (3.73 (95%CI: 2.50-5.56)), respectively. These measurements for overall survival (OS) were MTV (4.39 (95%CI: 2.71-7.08)), DS (3.23 (95%CI: 1.87-5.58)), and DS (3.64 (95%CI: 1.40-9.43)), respectively. Early and late 18F-FDG PET/CT response assessment in immune checkpoint inhibitors (ICI) and immune cell therapy might be an effective tool for prediction of clinical outcome. CONCLUSION: For anti-CD20 therapy of lymphoma, the MTV as a baseline 18F-FDG PET/CT-derived parameter has the highest HRs for PFS and OS. The DS as visual criteria in early and late response assessment has higher HRs for PFS and OS compared to the international harmonization project (IHP) visual criteria in anti-CD20 therapy. Early changes in 18F-FDG PET parameters may be predictive of response to ICIs and cell therapy in lymphoma patients.

Could Fibroblast Activation Protein (FAP)-Specific Radioligands Be Considered as Pan-Tumor Agents?

Background: Cancer-associated fibroblasts (CAFs) can strongly modulate the response to therapy of malignant tumor cells, facilitating their continuous proliferation and invading behaviors. In this context, several efforts were made in identifying the fibroblast activation protein (FAP) as a CAF recognizer and in designing FAP-specific PET radiotracers (as 68Ga-FAPI) along with FAP-specific therapeutic radioligands. Herein, we review different clinical studies using the various FAP-specific radioligands as novel theranostic agents in a wide range of oncologic and nononcologic indications. Methods: A comprehensive systematic search was conducted on the PubMed and Scopus databases to find relevant published articles concerning the FAP-specific PET imaging as well as the FAP-specific radionuclide therapy in patients with oncologic and nononcologic indications. The enrolled studies were dichotomized into oncologic and nononcologic categories, and the required data were extracted by precisely reviewing the whole text of each eligible study. A meta-analysis was also performed comparing the detection rates of 68Ga-FAPI vs. 18F-FDG PET/CT using odds ratio (OR) and risk difference as outcome measures. Results: Of the initial 364 relevant papers, 49 eligible articles (1479 patients) and 55 case reports were enrolled in our systematic review. These studies observed high radiolabeled FAPI avidity as early as 10 minutes after administration in primary sites of various malignant tumors. Based on the meta-analysis which was done on the reported detection rates of the 68Ga-FAPI and 18F-FDG PET/CT scans, the highest OR belonged to the primary lesion detection rate of gastrointestinal tumors (OR = 32.079, 95% CI: 4.001-257.212; p = 0.001) with low heterogeneity (I2 = 0%). The corresponding value of the nodal metastases belonged to hepatobiliary tumors (OR = 11.609, 95% CI: 1.888-71.365; p = 0.008) with low heterogeneity (I2 = 0%). For distant metastases, the highest estimated OR belonged to nasopharyngeal carcinomas (OR = 77.451, 95% CI: 7.323-819.201; p < 0.001) with low heterogeneity (I2 = 0%). Conclusions: The outperformance of 68Ga-FAPI PET/CT over 18F-FDG PET/CT in identifying certain primary tumors as well as in detecting their metastatic lesions may open indications for evaluation of cases with inconclusive 18F-FDG PET/CT findings. What needs to be emphasized is that the false-positive results might be problematic and must be taken into account in 68Ga-FAPI PET/CT interpretation. More clarification on the role of FAPI radioligands in oncologic imaging, radionuclide therapy, and radiotherapy treatment planning is therefore required.

Head-to-Head Comparison of Fibroblast Activation Protein Inhibitors (FAPI) Radiotracers versus [18F]F-FDG in Oncology: A Systematic Review.

Several recent studies comparing radiolabeled fibroblast activation protein inhibitors (FAPI) and fluorine-18 fluorodeoxyglucose ([18F]F-FDG) as positron emission tomography (PET) radiotracers in oncology have been published. The aim of this systematic review is to perform an updated evidence-based summary about the comparison of these PET radiotracers in oncology to better address further research in this setting. Studies or subsets of studies comparing radiolabeled FAPI and [18F]F-FDG as PET radiotracers in oncology were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until August 2021. Literature data about the comparison of [18F]F-FDG and radiolabeled FAPI are rapidly increasing. Overall, taking into account radiotracer uptake and tumor-to-background uptake ratio, compared to [18F]F-FDG PET, an equal or higher detection of primary tumors and/or metastatic lesions was usually demonstrated by using radiolabeled FAPI PET. In particular, the cancer entities with better detection rate of tumor lesions by using radiolabeled FAPI PET, compared to [18F]F-FDG PET, were gastrointestinal tumors, liver tumors, breast cancer and nasopharyngeal carcinoma. Further comparison studies are needed to better evaluate the best field of application of radiolabeled FAPI PET.

The value of 18F-FDG PET/CT for predicting or monitoring immunotherapy response in patients with metastatic melanoma: a systematic review and meta-analysis.

PURPOSE: To investigate the ability of 18F-FDG PET/CT to assess the response of patients with metastatic melanoma to immunotherapy. METHODS: A comprehensive search of the literature for studies examining the prognostic value of 18F-FDG PET/CT in monitoring the response of patients with metastatic melanoma to immunotherapy was performed. We also screened the references of the selected articles to identify any other relevant studies. Detailed data were extracted and categorized. Comprehensive meta-analysis software was used for analysis. RESULTS: Twenty four eligible articles were included in the systematic review. Based on the baseline 18F-FDG PET/CT imaging, the pooled hazard ratios of MTV, SLR, SUV/SULmax, SUV/SULpeak, and TLG for overall survival (OS) were 1.777 (95%CI: 1.389-2.275, p < 0.001), 3.425 (95%CI: 1.707-6.869, p = 0.001), 0.941 (95%CI: 0.599-1.477, p = 0.791), 1.704 (95%CI: 1.253-2.316, p = 0.016), and 1.755 (95%CI: 1.315-2.342, p < 0.001), respectively. The conventional and modified response assessment criteria exhibited a pooled sensitivity of 64% (95%CI: 46-79%) and 94% (95%CI: 81-99%) and a pooled specificity of 80% (95%CI: 59-93%) and 84% (95%CI: 64-95%), respectively, for the early 18F-FDG PET/CT scan. On the other hand, based on the late 18F-FDG PET/CT scan, the pooled sensitivity of 67% (95%CI: 35-90%) and 92% (95%CI: 73-99%) and pooled specificity of 77% (95%CI: 56-91%) and 76% (95%CI: 50-93%) were observed for the conventional and modified criteria, respectively. PET-detectable immune-related adverse events (irAEs) were associated with the response to therapy. CONCLUSIONS: The baseline SUVpeak, MTV, and TLG parameters represent promising predictors of the final response of metastatic melanoma patients to immunotherapy. Modified response assessment criteria are potentially an appropriate method for monitoring immunotherapy. irAEs are also valuable for predicting eventual clinical benefit of treatment.

Physiological distribution of 18F-FDG in the spinal cord: A systematic review.

Context: The importance of physiologic distribution of 18F-FDG in the spinal cord.Objective: The recognition of the physiologic distribution of 18F-FDG in the spinal cord is pivotal for accurate PET/CT imaging interpretation, especially in oncologic patients. Therefore, we performed a systematic review to investigate the normal distribution of 18F-FDG throughout the spinal cord.Methods: Data sources: We carried out a comprehensive search of the literature on the physiologic patterns of 18F-FDG distribution in the spinal cord. PubMed and Scopus databases were searched using the following keywords: "spinal cord" AND "FDG". Data extraction: Findings of the selected articles were described.Results: Thirteen studies comprising 24,125 patients entered the systematic review. These investigations showed discrepancies in location, size, number, and intensity of 18F-FDG uptake throughout the spinal cord. However, cumulative results showed that 18F-FDG uptake was higher in the lower thoracic portion of spinal cord (T11-T12). Moreover, a decreasing trend in 18F-FDG uptake was observed from cervical to lumbar levels. Low maximal standardized uptake values, female sex, and higher body weight seem to be related to the physiological spinal cord 18F-FDG uptake.Conclusions: On 18F-FDG PET/CT imaging, focal hypermetabolism of the spinal cord at the level of lower thoracic and lower cervical vertebrae should be considered physiological until proven otherwise.

Effect of Different 131I Dose Strategies for Treatment of Hyperthyroidism on Graves' Ophthalmopathy.

PURPOSE: The study aims to define the effect of different dose strategies on ophthalmic complications in patients with Graves' disease (GD). METHODS: All the patients with GD and no or inactive ophthalmopathy (clinical activity score; CAS < 3) underwent Snellen chart examination, measurement of proptosis, thyroid volume, and radioactive iodine uptake, and randomized into 1 of 3 groups. In group 1, all the patients received fixed low dose (FLD) of 259 MBq of I, whereas in group 2, all the patients received fixed high dose (FHD) of 555 MBq, and in group 3, calculated dose (CD) was administered to deliver 5.55 MBq/g (thyroid weight) of I. All examinations were repeated 6 months after treatment. The measurement of thyroid function tests and clinical examination were repeated after 12 months. RESULTS: We studied 92 patients (58 female and 34 male) with mean age of 38.2 ± 12.0 years. Overall, 29, 32, and 31 patients were studied in FLD, FHD, and CD groups, respectively. The patients in CD received a mean activity of 240.5 MBq. The 3 groups were not significantly different regarding age, sex ratio, radioactive iodine uptake, smoking, visual acuity, and proptosis. The response rate 12 months after radioactive iodine therapy was 66.7%, 94.4%, and 92.9% in FLD, FHD, and CD groups, respectively (P = 0.05). Overall, CAS was increased significantly after treatment. Delta proptosis and delta CAS were increased significantly in FHD group compared with other groups (P < 0.05). The highest increment in proptosis was seen in FHD group. CONCLUSIONS: The administration of 5.55 MBq/g of I has fewer ophthalmic complications compared with high fixed dose model and is more effective than low fixed dose strategy.

Application of 99mTc-UBI 29-41 scintigraphy in knee periprosthetic infection diagnosis.

AIM: In recent years, the use of total knee arthroplasty (TKA) is considered a safe and cost-effective orthopedic procedure for alleviating the chronic pain and treatment of progressive osteoarthritis. This procedure may have some complications including periprosthetic infection as the most serious and aseptic loosening as the most common one. Differentiating between these entities is important because each has a different therapeutic approach. This study was conducted to investigate the ability of 99mTC-UBI scan to distinguish septic from aseptic loosening in a painful knee prosthesis. METHODS: 34 patients with painful knee prostheses were included. The 99mTC-UBI scan was done immediately after IV administration of 99mTC-UBI in early dynamic and 30-minute static images. Time-activity curve (TAC) was drawn for all patients and target to non-target ratio (T/NT) was calculated on 30-minute images. The final diagnosis was confirmed by surgical findings, microbiologic culture results or active clinical follow up. RESULTS: Using TAC analysis, 24 99mTC-UBI scans were considered negative and 10 positive for an infectious process. Sensitivity, specificity, negative and positive predictive values were 56 %, 80 %, 83 %, and 50 %, respectively. T/NT ratio analysis on 30-minute static images demonstrated 9 positive and 25 negative patterns, with a cut off value of 1.83 for the T/NT ratio. The sensitivity, specificity, negative and positive predictive values, and accuracy of this test modality were all 100 %. CONCLUSIONS: Our findings show 99mTc-UBI scan is an excellent clinical diagnostic test for differentiating septic from aseptic loosening of the knee prostheses with perfect sensitivity and specificity. Highly accurate results were obtained only 30 minutes after injection.

Benign High-Flow Priapism With a Diffuse and Intense 18F-FDG Uptake on 18F-FDG PET/CT Scanning.

We present benign high-flow priapism with intensive F-FDG uptake as an unusual finding in a case of testicular teratocarcinoma with a history of left orchiectomy and chemotherapy. F-FDG PET/CT scan showed pulmonary metastases, left obturator node involvement, and intense F-FDG uptake in the penis. Upon examination, the patient had a painless erection that lasted for couple of days. Because of pulmonary metastases, second-line chemotherapy regimen was started by his physician. The patient's priapism resolved spontaneously, with no episode of recurrence at 2 years' follow-up.

68Ga DOTATATE PET/CT Versus 18F-FDG PET/CT for Detecting Intramedullary Hemangioblastoma in a Patient With Von Hippel-Lindau Disease.

Von Hippel-Lindau disease is an inherited syndrome associated with several benign and malignant tumors such as central nervous system (CNS) hemangioblastoma. Herein, we report a known case of A Von Hippel-Lindau patient with a cerebral hemangioblastoma who was referred for further evaluation because of recent paraparesis. F-FDG PET/CT showed no focal uptake in the thoracic spine, which demonstrated increased Ga DOTATATE activity, owing to overexpression of somatostatin receptors, suggesting spinal cord hemangioblastoma. This case report indicates the significant role of Ga-labeled somatostatin receptor analogs in the diagnosis of hemangioblastoma.

99mTC-MDP bone scanning in a subungual glomus tumour.

A 37-year-old female patient with four months history of paroxysmal pain in the left index finger was referred to our department for 99mTC-MDP scintigraphy. Radiographic studies of the patient showed a lytic tumour in the distal phalanx of the left second finger compatible with a glomus tumour. The scan showed mild decreased activity in the blood pool phase and minimal increased activity on the delayed images. The patient underwent surgery and a glomus tumour was removed. To the extent of our knowledge, this is the first case of bone scan in a glomus tumour of the finger reported in the literature.