FAPI PET/CT Imaging-An Updated Review.

Despite revolutionizing the field of oncological imaging, Positron Emission Tomography (PET) with [18F]Fluorodeoxyglucose (FDG) as its workhorse is limited by a lack of specificity and low sensitivity in certain tumor subtypes. Fibroblast activation protein (FAP), a type II transmembrane glycoprotein, is expressed by cancer-associated fibroblasts (CAFs) that form a major component of the tumor stroma. FAP holds the promise to be a pan-cancer target, owing to its selective over-expression in a vast majority of neoplasms, particularly epithelial cancers. Several radiolabeled FAP inhibitors (FAPI) have been developed for molecular imaging and potential theranostic applications. Preliminary data on FAPI PET/CT remains encouraging, with extensive multi-disciplinary clinical research currently underway. This review summarizes the existing literature on FAPI PET/CT imaging with an emphasis on diagnostic applications, comparison with FDG, pitfalls, and future directions.

Diagnostic performance of Ga-68 FAPI 04 PET/CT in colorectal malignancies.

AIM: To evaluate the role of Ga-68 fibroblast activation protein inhibitor 04 PET/computed tomography (FAPI) in colorectal cancers (CRCs) in terms of diagnostic accuracy and impact on clinical management. FAPI is compared with FDG PET/CT and conventional imaging in staging, restaging, recurrence detection, and response evaluation of CRC. METHODS: Twenty-nine consecutive patients of histopathologically confirmed primary or relapsed CRC were included in the study. Patients who underwent FAPI PET/CT along with either FDG PET/CT or conventional imaging were included. Primary lesions, recurrence sites, lymph nodes, and metastatic lesions were recorded on all the scans. Maximum standardized uptake value (SUVmax) was measured from both primary and metastatic lesions. RESULTS: The sensitivity of FAPI in primary and recurrence detection is 100% compared to 88% for FDG/conventional imaging. The overall sensitivity of FAPI stands at 98% with accuracy at 95% whereas for FDG/conventional imaging the sensitivity and accuracy are 78% and 77%, respectively, with P < 0.002. Significant difference was noted in the detection of peritoneal metastasis (96% vs. 66%). CONCLUSION: FAPI PET/CT shows better sensitivity and accuracy in the evaluation of CRCs, especially in peritoneal disease compared to FDG PET/CT and conventional imaging. FAPI has the potential to replace FDG in CRCs.

Non Target Shunting of Tc-99m Macroaggregates of Albumin and Radiolabeled Yttrium-90 Microspheres into Hepatic Falciform Artery - Less Observed Arterial Variant not to be Overlooked.

Identification of nontarget arteries is crucial prior to Yttrium-90 microspheres radioembolization. We present a case where an uncommon nontarget artery, the hepatic falciform artery was identified during work up for radioembolization and necessary preventive measures were taken to minimize the complications.

Sub-Diaphragmatic Haemangioma Suspected on F-18 Fdg Pet/Ct Confirmed by Rbc Scintigraphy.

A 53-year-old woman presented with left submandibular gland carcinoma. Contrast-enhanced computerized tomography done for staging revealed suspicious metastatic omental deposit adjacent to left hemi-diaphragm apart from primary and cervical nodal metastasis. Staging F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography showed high FDG uptake in the primary and metastatic left cervical lymph nodes. However, no FDG uptake was seen in left sub-diaphragmatic mass. Known vascular malformations sites in the left posterior triangle of the neck and liver hemangiomas also showed no uptake. This pattern of uptake raised a suspicion of multiple vascular malformations. Tc-99 m red blood cell scintigraphy was done which confirmed the nature of subdiaphragmatic lesion as haemangioma.

Unusual Case of Neuroblastoma with Only Growth Plate Metastasis in Bilateral Lower Limbs on Metaiodobenzylguanidine Scintigraphy.

Neuroblastoma is the most common extracranial solid tumor in childhood developing from primitive neural crest cells. I-131-metaiodobenzylguanidine (MIBG) a norepinephrine analog is highly sensitive and specific to identify primary and distant metastatic sites. We report the case of a 2-year-old female child with progressively increasing abdominal distention. Computed tomography (CT) revealed a large mass lesion involving the right suprarenal region with no hepatic or lymph node metastasis. No obvious skeletal abnormality was detected on the whole-body skeletal survey and Tc-99 m-methylene diphosphonate bone scan to suggest metastasis. I-131-MIBG scintigraphy with single-photon emission computerized tomography-CT showed MIBG-avid primary tumor in a suprarenal location with bilateral lower limbs growth plate as the only site of metastasis.

Role of 99mTc sulphur colloid lymphoscintigraphy in a rare case of chylothorax and lymphocele formation post esophageal duplication cyst excision.

We report a rare case of chylothorax with lymphocele formation post esophageal duplication cyst (EDC) excision in a 2 year old male child. Patient developed chylothorax after excision of EDC. Pleural fluid cytology showed increased triglycerides and cholesterol levels. Filtered Tc-99m Sulphur colloid lymphoscintigraphy showed abnormal radiotracer uptake in the lower thoracic region on right side corresponding to lymphocele on SPECT-CT images with possible site of leak medially. In addition, Tc-99m pertechnetate scan was done to rule out possibility of residual duplication cyst revealed no abnormality. Patient underwent open and en-masse ligation of the duct. Patient recovered completely post-surgery. This case highlights the importance of lymphoscintigraphy with SPECT-CT in the evaluation of patients with post-operative complications of chylothorax with detection of site of chyle leak.

Fusion 68Ga-DOTANOC PET/MRI in Primary Juvenile Nasal Angiofibroma.

ABSTRACT: Somatostatin cell surface receptors are expressed in many different benign and malignant tumors and are often exploited for imaging and therapy of neuroendocrine tumors. A 17-year-old adolescent boy with clinicoradiologically diagnosed JNA (juvenile nasopharyngeal angiofibroma) also underwent 68Ga-DOTANOC PET to explore somatostatin cell surface receptors' expression and its theranostic potential. Fusion PET/MRI, a novel imaging technology, exactly depicted the anatomical extensions of the tumor with avid DOTANOC uptake. This software-based fusion technique is advantageous for easy early recurrence identification, better delineation from postoperative scar tissue, for planning the exact target volumes for stereotactic radiotherapy therapy of inoperable/residual/recurrent JNAs in the future.

Physiological PSMA Uptake in the Tubarial Salivary Glands and Its Implications in the PARIS Protocol-A First Study of Its Kind!

OBJECTIVES: Because prostate-specific membrane antigen (PSMA) expression is universal in juvenile nasal angiofibroma (JNA), PSMA PET/CT is commonly used in the postoperative setting using the postoperative angiofibroma radionuclide imaging study protocol. Our study aims to illustrate physiological PSMA ligand uptake distribution characteristics in the salivary glands, specifically the tubarial glands with tumor, to aid in accurate PSMA PET/CT analysis. STUDY DESIGN: Forty-three consecutive patients who underwent a dedicated head and neck spot PSMA PET/CT for JNA were evaluated retrospectively. PSMA SUVmax values in the tumor, tubarial, parotid, submandibular, and sublingual salivary glands were determined visually and quantitatively. RESULTS: All the tumors and the salivary glands showed increased tracer uptake. The median SUVmax ± SD ratios of the tumor, right and left tubarial gland, right and left parotid gland, right and left submandibular gland, and right and left sublingual gland were 2.7 ± 0.8 (range, 0.5-7.5), 3.8 ± 1.9 (range, 0.9-8.1), 4.7 ± 2.1 (range, 0.8-7.4), 9.5 ± 4.8 (range, 3.2-21.9), 9.2 ± 4.7 (range, 2.9-18.9), 10.4 ± 5.7 (range, 3.5-25.4), 10.4 ± 5.5 (range, 3.7-26.4), 6 ± 4.1 (range, 1.3-20.6), and 6.5 ± 4.2 (range, 1.8-19.7), respectively. The uptake in the tubarial glands was comparable with that of the tumor but less compared with other major salivary glands. CONCLUSIONS: Ours is the first study demonstrating the quantitative uptake of tubarial salivary glands in detail. Because the tubarial glands uptake and the anatomical location are similar to that of the tumor, these physiological uptakes must be borne in mind to circumvent false-positive interpretations and care must be given during the planning of stereotactic radiotherapy for JNAs.

Validation of Postoperative Angiofibroma Radionuclide Imaging Study (PARIS) Protocol Using PSMA PET/CT-A Proof of Concept Study.

OBJECTIVES: Juvenile nasopharyngeal angiofibroma (JNA) expresses prostate-specific membrane antigen (PSMA), and PSMA PET/CT scan may be used for its imaging. Also, the precise diagnosis of residual/recurrent JNA after surgical treatment remains difficult with conventional contrast MRI and/or CT; functional imaging with PSMA PET/CT promises greater accuracy in the detection or exclusion of recurrent/residual JNA. PATIENTS AND METHODS: In this prospective study, 22 postoperative JNA patients who underwent a PSMA PET/CT scan both preoperatively and postoperatively from January 2018 to September 2020 were included. All patients underwent a low-dose head and neck spot PET/CT imaging. Abnormal postcontrast enhancement of a definite lesion was considered residual/recurrent tumor in contrast-enhanced MRI (CEMRI). In PSMA PET/CT, any abnormal uptake apart from physiological sites in the head and neck was considered as residual lesions. Radiological results were categorized as negative, suspicious for residual lesions, or definite residual/recurrent tumors. PSMA PET/CT findings were considered as the radiological standard, and patients were managed accordingly. The sensitivity, specificity, positive predictive value, and negative predictive value were separately calculated for CEMRI and PSMA PET/CT for diagnosing residual lesions. RESULTS: On postoperative CEMRI evaluation, 12 patients had residual tumors, 2 had normal suspicious scans, and 8 had normal postoperative scans. On PSMA PET/CT, only 7 patients had residual tumors and 15 had normal postoperative scans. In 1 patient with a residual tumor on both scans, a discrepancy was noted concerning tumor extent, and PSMA PET/CT accurately mapped the tumor. The sensitivity, specificity, positive predictive value, and negative predictive value of CEMRI were 100%, 53.33%, 41.67%, and 100%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of PSMA PET/CT were 100% for all parameters. CONCLUSIONS: Because CEMRI is oversensitive and less specific compared with PSMA PET/CT, Postoperative Angiofibroma Radionuclide Imaging Study (PARIS) protocol should be used always. In residual tumors, PSMA PET/CT has an outright advantage over CEMRI in the diagnosis, tumor mapping, decision making, planning stereotactic radiation, and aiding in future follow-ups.

Clinical utility of Ga68 DOTANOC PET/CT imaging in juvenile nasal angiofibroma and the PARIS protocol: a preliminary report.

OBJECTIVES: Juvenile nasopharyngeal angiofibroma (JNA) expresses different somatostatin cell surface receptors and Ga68 [DOTA, 1-Nal3]-octreotide (DOTANOC)-PET/computed tomography (CT) scan may be used for its imaging. Also, functional imaging with DOTANOC-PET/CT may promise of greater accuracy in the detection or exclusion of recurrent/residual JNA. METHODS: In this prospective study, five JNA patients who underwent a DOTANOC-PET-CT scan both preoperatively and postoperatively during June 2018-March 2020 were included. Postcontrast enhancement of a definite lesion was considered residual/recurrent tumor in contrast-enhanced MRI (CEMRI). In DOTANOC-PET/CT, any abnormal uptake apart from physiological sites was considered as residual lesions. Radiological results were categorized as negative, suspicious or definite residual/recurrent tumors. Any discrepancy was resolved by endoscopic biopsies. RESULTS: Preoperatively all five cases of JNA showed avid DOTANOC expression in the tumor. The mean (SD) value of DOTANOC standardised uptake value in the tumor was 4.3 (1.4) (range = 2.1-6.2). In postoperative CEMRI evaluation, three of five patients had residual tumors and two had normal scans. On DOTANOC-PET/CT, two of five patients had residual tumors and three had normal scans. In one patient with residual tumor, the discrepancy with regard to tumor extent was noted in two scans, and further biopsy confirmed the findings of DOTANOC-PET/CT as accurate. CONCLUSION: 68Ga-DOTANOC-PET/CT uptake is universal in JNA and appears to be more specific in the identification of residual/recurrent JNA. In residual tumors, DOTANOC-PET/CT may have an advantage over CEMRI in the diagnosis, decision making and planning stereotactic radiation. However, these findings are to be validated in studies with larger patients.

68 Ga DOTANOC PET/CT Scan in Primary Juvenile Nasopharyngeal Angiofibroma - A Pilot Study.

OBJECTIVES/HYPOTHESIS: Somatostatin receptors (SSTRs) are highly expressed in neuroendocrine tumors and is exploited for its imaging and treatment. SSTRs expression is also demonstrated in diverse benign and malignant tumor cell types and proliferating peri-tumoral vessels. Similarly, Juvenile Nasopharyngeal Angiofibroma (JNA) expresses different SSTRs and may be utilized for its imaging and treatment using DOTA, 1-Nal3-octreotide (DOTANOC)-PET/CT scan. STUDY DESIGN: Prospective cohort. METHODS: Nineteen clinico-radiologically diagnosed primary JNA patients underwent a 68 Ga-DOTANOC PET-CT scan. Using a dedicated PET/CT scanner, a low-dose head and neck spot CT scan was performed after 45 to 60 minutes of intravenous injection of 2 to 3 mCi(74-111 MBq) of DOTANOC. The primary objective was to assess the intensity and pattern of DOTANOC uptake in these patients. RESULTS: DOTANOC expression was noted in all cases (n = 19) of primary JNA (100%). The mean (SD) DOTANOC SUVmax ratio of tumor and background was 6.9+/-1.4(range, 3.8-9.5). Intra-cranial extension in all 13/19 patients was prominently visualized due to the absence of DOTANOC uptake in the brain. Compared to the background all stages of JNA showed significant DOTANOC uptake (P < .0001). No difference in uptake between advanced-stage tumors and early tumors was noted (P = .47). A statistically non-significant negative trend was noted for decreasing uptake with increasing age (Spearman correlation coefficient, r = -0.19). CONCLUSIONS: This first study of 68 Ga-DOTANOC-PET/CT scan in JNA demonstrates consistent and reliable uptake activity in all patients irrespective of age and stage. This opens up possibilities to physiological diagnostic imaging with a promise of greater specificity and sensitivity and may have applications in ambivalent diagnostic situations such as the detection of recurrence. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1509-1515, 2021.

Intraosseous Medullary Fat Necrosis on 99mTc-MDP Bone Scan of Patient With Acute Pancreatitis.

Pancreatic disease can be associated with polyarthritis and panniculitis in a small number of patients, and this triad constitutes PPP syndrome. Early diagnosis is critical as it has high morbidity and mortality. Panniculitis can occur in fat present anywhere in the body. Involvement of fat in bone marrow is relatively uncommon, and radiologic imaging shows osteolytic lesions involving long bones. Here we present a case of acute pancreatitis, referred to our department for evaluation of severe joint pain and multiple bone pain. Tc-MDP scan with SPECT/CT has been done, which showed medullary expansion with heterogenous tracer uptake, that is, moth-eaten appearance.

Clinical Utility of 68Ga-Prostate-Specific Membrane Antigen PET/CT Scan on Postoperative Assessment of Juvenile Nasal Angiofibroma.

Prostate-specific membrane antigen (PSMA) is expressed on the endothelial cells of tumor-associated neovasculature of various nonprostatic benign and malignant neoplasms. Positive uptake on PET/CT imaging with Ga-labeled PSMA is noted in a patient with juvenile nasal angiofibroma, and the same is noted to be absent following complete surgical excision. Ga-PSMA PET/CT may be a useful tool for juvenile nasal angiofibroma recurrence identification and in differentiating recurrence from surgical site reparative tissue.

Evaluation of estrogen expression of breast cancer using 18F-FES PET CT-A novel technique.

Estrogen receptor (ER) expression in breast cancer is routinely studied on immunohistochemistry (IHC) of tissue obtained from core biopsy or surgical specimen. Sampling error and heterogeneity of tumor may incorrectly label a breast tumor as ER negative, thus denying patient hormonal treatment. Molecular functional ER imaging can assess the in-vivo ER expression of primary tumor and metastases at sites inaccessible for biopsy and also track changes in expression over time. The aim was to study ER expression using 16α-18F-fluoro-17ß-estradiol or 18F-fluoroestradiol (18F FES) positron emission tomography (PET) computed tomography (CT). Twenty-four biopsy-proven breast cancer patients consenting to participate in the study underwent FES PET CT. Standard uptake value (SUVmean) of maximum of 7 lesions/patient was analyzed, and tumor-to-background ratio was calculated for each lesion. Visual interpretation score was calculated for lesion on FES PET and correlated with the Allred score on IHC of tumor tissue samples for ER expression. The diagnostic indices of FES PET CT were assessed taking IHC as "gold standard." On FES PET CT, the mean SUV for ER+ tumors was 4.75, whereas the mean SUV for ER - tumors was 1.41. Using receiver operating characteristic curve, tumors with an SUV of ≥ 1.8 on FES PET could be considered as ER+. The overall accuracy of FES PET CT to detect ER expression was 91.66%, with two false negatives noted in this study. 18F-FES PET CT appears promising in evaluating ER expression in breast cancer. It is noninvasive and has potential to assess the in-vivo ER expression of the entire primary tumor and metastasis not amenable for biopsy.

Clinical Utility of 68Ga-DOTANOC Positron Emission Tomography-Computed Tomography Scan on Postoperative Assessment of Juvenile Nasal Angiofibroma.

Somatostatin cell surface receptors are expressed on the peritumoral vessels of various benign and malignant neoplasms including angiofibromas. Positive initial uptake on positron emission tomography-computed tomography (PET/CT) imaging with 68Ga-labeled DOTANOC is noted in a patient with juvenile nasal angiofibroma (JNA), and the same is noted to be absent following complete surgical excision. Functional 68Ga-DOTANOC PET/CT may be an early useful tool for JNA residual/recurrence identification and precise postoperative surveillance.

Juvenile Nasal Angiofibroma on 68Ga-DOTANOC PET/CT: Exploring Theranostic Avenues.

Somatostatin (SST) cell surface receptors (SSTRs) are expressed in many different malignant, benign, and neuroendocrine tumors. SSTRs are also expressed in the endothelium of human vessels during angiogenesis and not in the nonproliferating vessels. We present a case of 19-year-old boy with juvenile nasal angiofibroma (JNA), who underwent 68Ga-DOTANOC PET/CT to explore SSTRs expression and theranostic potential. The scan revealed high uptake in the tumor, and in certain areas, the uptake was similar to that of the pituitary gland. Performance of DOTANOC PET/CT in JNA opens up new frontiers with respect to radiological staging, early recurrence identification, better delineation from postoperative scar tissue, possible preoperative treatment with SST analogs, and perhaps even radiopharmaceutical based-ligand therapy of inoperable/residual/recurrent JNAs in the future.

Comparison of 68Ga-PSMA PET/CT and Contrast-Enhanced MRI on Residual Disease Assessment of Juvenile Nasal Angiofibroma.

Prostate-specific membrane antigen (PSMA) is expressed in the endothelial cells of tumor-associated neovasculature of various nonprostatic benign and malignant neoplasms including juvenile nasopharyngeal angiofibroma (JNA). Positive uptake on PET/CT imaging with Ga-labeled PSMA is noted in a patient with residual disease after initial surgery without any abnormal uptake in postoperative fibrosis, in contrast to contrast-enhanced MRI, which was confirmed by biopsy. Ga-PSMA PET/CT may be a useful tool clinically for identifying early biochemical recurrences and in specifically differentiating recurrences from surgical site reparative tissue.

Robotic-assisted computed tomography-guided 18F-FDG PET/computed tomography-directed biopsy for diagnosis of intra thoracic lesions: An experience from a tertiary care centre in North India.

OBJECTIVE: The aim of this study was to assess the diagnostic yield of robotic-assisted computed tomography (CT)-guided F-FDG PET/CT-directed biopsy for the evaluation of intrathoracic space occupying lesions. METHODS: Twenty-four patients being evaluated for intrathoracic masses were included in the study. The indications were patients with unknown/likely primary detected from PET-CT, suspicious lesions identified from PET-CT in a known primary disease and fine needle aspiration cytology/CT-guided biopsy negative lesions with a high index of suspicion for malignancy. Biopsies were carried out with the help of automated radiology arm (ROBIO-EX) which is essentially a needle positioning and holding device. A two-day protocol was followed in which PET-CT scan was done on the first day, biopsy procedure was done on the next scheduled day. PET images were refused with the CT images done on the second day in the console by using manual alignment and then a biopsy was carried out with the help of a robotic arm. Primary outcome was histopathological yield from the obtained specimens. RESULTS: Tissue yield was 100% (n = 24) and histopathological diagnosis rate was 96% (n = 23). Out of the 24 lesions biopsied 30% (n = 8) were benign and 70% (n = 16) turned out to be malignant. The complication rates were pneumothorax 4% (n = 1) and haemothorax 4% (n = 1). CONCLUSION: Robotic-assisted CT-guided F-FDG PET/CT-directed biopsy is a useful and accurate technique for diagnostic evaluation of intrathoracic neoplasms with minimal complications rates as compared with conventional imaging techniques.

Clinical Applications of 68Ga-PSMA PET/CT on Residual Disease Assessment of Juvenile Nasopharyngeal Angiofibroma (JNA).

We present a case of a 16-year-old boy who underwent 68Ga-PSMA PET/CT for residual disease assessment of juvenile nasal angiofibroma. Positive uptake was noted in residual tumor on PET/CT imaging. However, there was no abnormal uptake in surrounding scar tissues as compared with contrast-enhanced magnetic resonance imaging. These findings were confirmed by biopsy from the scar tissue on posterior ethmoids. 68Ga-PSMA PET/CT may be a potentially valuable tool especially in distinguishing recurrences from surgical site reparative tissue and in planning and delivering stereotactic radiotherapy.

Prostate-Specific Membrane Antigen Expression in Primary Juvenile Nasal Angiofibroma-A Pilot Study.

PURPOSE: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and is exploited for imaging and treatment of patients with prostate cancer. Prostate-specific membrane antigen expression is also demonstrated in the tumor-associated neovasculature endothelium. Juvenile nasal angiofibroma (JNA), being a similar highly vascular tumor, may also demonstrate significant PSMA expression, which may be utilized for its imaging and treatment. METHODS: In this prospective study, 25 clinicoradiologically diagnosed primary JNA patients underwent PSMA PET/CT scan. The scan was performed after 45 to 60 minutes of intravenous injection of 2 to 3 mCi (74-111 MBq) of Ga-PSMA-HBED-CC on a dedicated PET/CT scanner. Low-dose CT scan was acquired from vertex to sternoclavicular joint (100 mA, 20 kVp, 3-mm slice thickness, 0.8 pitch). Images were reconstructed with iterative reconstruction technique (4 iterations, 24 subsets). The objective was to assess the intensity and pattern of PSMA uptake in primary JNA patients. RESULTS: All cases (n = 25) of primary JNA showed PSMA expression in the tumor (100%). The median PSMA SUVmax ratio of tumor to background was 4.57 (range, 2.08-7.27). Intracranial extension in 14 of 25 patients was prominently visualized because of absence of background uptake in the brain. Advanced stage tumors demonstrated greater uptake than early tumors (P = 0.011). A statistically nonsignificant trend was noted for decreasing uptake with increasing age after normalizing for stage (Spearman correlation coefficient r = -0.08). CONCLUSIONS: Assessment of PSMA expression in JNA by PSMA PET/CT opens up a new window of opportunity with respect to its radiological staging, vascularity assessment, and molecular characterization. A potential role in identification of the difficult residual-recurrent disease is anticipated and perhaps also in radioligand therapy for residual/recurrent JNA.Clinical Trials Registry of India (CTRI/2018/08/015479).