Initial clinical experience using 68Ga-FAPI-46 PET/CT for detecting various cancer types.

OBJECTIVE: Numerous studies have shown that gallium-68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) scans would yield high intra-tumoral tracer uptake and low uptake in normal tissues as background, thus allowing for excellent visualization of lesions in the cancer microenvironment. This study set out to compare the suitability of novel 68Ga-FAPI-46 PET versus routine fluorine-18-fluorodeoxyglucose (18F-FDG) PET and other few cases of 68Ga-DOTATATE/68Ga-Pentixafor PET/CT for the assessment of different types of cancer. SUBJECTS AND METHODS: A retrospective analysis of 11 patients (6 males, 5 females; average age: 53 years, range: 10-58 years) with histopathologically confirmed, well-differentiated adenocarcinoma, medullar thyroid cancer (MTC), papillary thyroid carcinoma (PTC), cervical, gastric, glioblastoma multiform (GBM), colon, Ewing's sarcoma, and breast cancer was performed. These patients underwent PET/CT scans using four different radiotracers (9 18F-FDG, 11 68Ga- FAPI, 3 68Ga-DOTATATE, and 1 68Ga-Pentixafor). The patients' PET/CT images were visually evaluated for cancer detection, and analyzed semi-quantitatively through image- derived metrics, such as target-to-background ratio (TBR) and maximum standardized uptake value (SUVmax), for recurrence and metastasis. RESULTS: The study of 11 patients revealed that 68Ga-FAPI-46 was more effective than other tracers for detecting metastases, with 55 vs. 49 metastases in the lymph nodes, 4 vs. 3 in the liver, and 4 vs. 3 in the bones detected in comparison to 18F-FDG. No significant differences were observed in 68Ga-DOTATATE and 68Ga-Pentixafor PET images. In addition, in five patients, the SUVmax and TBR values in 68Ga-FAPI-46 PET images were significantly higher than those in 18F-FDG PET images for lymph nodes and bone metastases. Although the SUVmax in 68Ga-FAPI-46 and 18F-FDG PET images for liver metastases was comparable, 68Ga-FAPI- 46 had a significantly higher TBR than 18F-FDG. CONCLUSION: Our findings suggest that FAPI PET/CT is not suitable for evaluating GBM and Ewing sarcoma but generally outperforms 18F-FDG PET/CT in various types of breast cancer, gastrointestinal, gynecological, PTC and MTC. However, larger trials are needed to validate these preliminary findings.

Prospective study of Na[18F]F PET/CT for cancer staging in morbidly obese patients compared with [99mTc]Tc-MDP whole-body planar, SPECT and SPECT/CT.

PURPOSE: This prospective study aims to assess the diagnostic test characteristics of Na[18F]F PET/CT for the skeletal staging of cancer in morbidly obese patients compared with 99mTc-methylene diphosphonate (MDP), whole-body planar (WBS), SPECT, and SPECT/CT acquisitions. MATERIAL AND METHODS: One hundred seventeen obese patients (BMI 46.5 ± 6.1 kg/m2 and mean age, 59.0 years; range 32-89 years) with BMI > 40 kg/m2 were prospectively enrolled and underwent [99mTc]Tc-MDP WBS, SPECT, SPECT/CT, and Na[18F]F PET/CT within two weeks for the osseous staging of a malignancy. Images were assessed qualitatively using a 3-point scale. Patient and lesion-based diagnostic test characteristics were estimated using an optimistic and pessimistic dichotomization method. RESULTS: Bone metastases were confirmed in 44 patients. Patient-based optimistic diagnostic test characteristics were (sensitivity, specificity, overall accuracy): Na[18F]F PET/CT (95.5%, 95.9%, 95.7%), [99mTc]Tc-MDP WBS (52.3%, 71.2%, 64.1%), SPECT (61.4%, 80.8%, 73.5%) and SPECT/CT (65.9%, 91.8%, 82.1%). Lesion-based optimistic diagnostic test characteristics were: Na[18F]F PET/CT (97.7%, 97.9%, 97.7%), [99mTc]Tc-MDP WBS (39%, 67%, 48.9%), SPECT (52.9%, 93.6%, 67.3%) and SPECT/CT (65.9%, 91.8%, 82.1%). There was no significant difference in the specificity of Na[18F]F and SPECT/CT. All other pairwise comparisons were significant (p<.001). ROC curve analysis showed a high overall accuracy of Na[18F]F with significantly higher AUCs for Na[18F]F PET/CT compared to [99mTc]Tc-MDP WBS, SPECT, and SPECT/CT on both patient and lesion-based analysis (p<.001). Moreover, Na[18F]F PET/CT changed patient management in 38% of patients. CONCLUSIONS: Na[18F]F PET/CT may be the preferred imaging modality for skeletal staging in morbidly obese patients. The technique provides excellent diagnostic test characteristics superior to [99mTc]Tc-MDP bone scan (including SPECT/CT), impacts patient management, has an acceptable radiation exposure profile, and is well-tolerated. Further cost-effectiveness evaluations are warranted.

Update on imaging in chronic kidney disease-mineral and bone disorder: promising role of functional imaging.

Disorders of mineral metabolism and bone disease are common complications in chronic kidney disease (CKD) patients and are associated with increased morbidity and mortality. Bone biopsies, bone scintigraphy, biochemical markers, and plain films have been used to assess bone disorders and bone turnover. Of these, functional imaging is less invasive than bone/marrow sampling, more specific than serum markers and is therefore ideally placed to assess total skeletal metabolism. 18F-sodium fluoride (NaF) PET/CT is an excellent bone-seeking agent superior to conventional bone scan in CKD patients due to its high bone uptake, rapid single-pass extraction, and minimal binding to serum proteins. Due to these properties, 18F-NaF can better assess the skeletal metabolism on primary diagnosis and following treatment in CKD patients. With the increased accessibility of PET scanners, it is likely that PET scanning with bone-specific tracers such as 18F-NaF will be used more regularly for clinical assessment and quantitation of bone kinetics. This article describes the pattern of scintigraphic/functional appearances secondary to musculoskeletal alterations that might occur in patients with CKD.

Primary Breast Lymphoma Mimicking Metastatic Breast Cancer on 18F-FDG PET-CT.

18F-Fluorodeoxyglucose (FDG) PET-CT is an excellent imaging modality for the evaluation of non-Hodgkin lymphoma (NHL). We report a case of a 45-year-old woman presented with a large right breast mass and suspicious right axillary lymph nodes referred for 18F-FDG PET-CT for staging. 18F-FDG PET-CT images show large hypermetabolic right breast mass infiltrating the skin, multiple hypermetabolic right axillary and subpectoral lymph nodes, along with multiple hypermetabolic bone lesions at axial and appendicular skeleton. Findings are mimicking primary breast cancer with nodal and bone metastases. Biopsy revealed diffuse large B cell lymphoma. 18F-FDG PETCT is helpful in evaluation of disease extent and response evaluation of primary breast lymphoma.

Spectrum of false positive 18F-sodium fluoride (NaF) bone PET/CT findings in Oncology imaging; A narrative pictorial review of cases from a single institution.

Fluorine-18-sodium fluoride (18F-NaF) is a positron emission tomography (PET) bone imaging agent mainly used for oncology staging but may also be used in the evaluation of benign bone and joint pathology conditions. Fluorine-18-NaF is an excellent bone-seeking agent with high bone uptake owing to favorable biodistribution with rapid single-pass extraction, limited plasma protein binding and prompt renal clearance. Fluorine-18-NaF PET/computed tomography (CT) is highly sensitive in identifying both sclerotic and lytic bone metastatic lesions. Occasionally 18F-NaF uptake in benign bone lesions can mimic malignantpathology. In these cases, the pattern of 18F-NaF uptake may elicit a specific diagnosis and correlation with clinical information and morphological information from correlative CT is essential for a correct diagnosis. In the present article, we present a series of clinical cases demonstrating examples of 18F-NaF uptake in benign lesions which can simulate malignant pathology in patients undergoing cancer staging.

Assessment of regional and total skeletal metabolism using 18F-NaF PET/CT in patients with chronic kidney disease.

OBJECTIVE: The study aims to assess regional and total bone metabolic activity in patients with chronic kidney disease using Na[18F]F PET and correlation between semi-quantitative indices and blood parameters. METHODS: Seventy-two subjects (mean age 61.8 ± 13.8 years) were included. Of these 24/72 patients had end-stage renal disease (ESRD) (GFR < 15 mL/min/1.73 m2), 38/72 had chronic kidney disease (CKD) (GFR between 60 and 15 mL/min/1.73 m2), and 10/72 were controls with normal renal function. All subjects underwent Na[18F]F PET-CT with a dose activity of 0.06 mCi/Kg. Regional and total skeletal metabolism were assessed with mean SUVs in a skeletal volume of interest (VOI), bone to soft tissue index (B/S), global SUV mean (GSUV mean) of the whole bone, and uptake in the femoral neck. RESULTS: Statistically significant differences were observed in a number of 18F-NaF metrics like femoral neck metabolism in CKD and ERSD groups in comparison to control in right (P = 0.003) and left femur (P = 0.006), bone to soft tissue index in the femur (P = 0.016) and GSUV5 (P = 0.006). There is also a significant difference in SUV mean in lumbar vertebrae (L1-L4) among CKD, ESRD, and controls. There was a moderate correlation between 18F-NaF PET scan uptake and blood parameters such as ALP and PTH. Na[18F]F uptake parameters were significantly different in low versus high bone turnover state. CONCLUSIONS: The assessment of total skeleton and regional metabolism and bone turnover in CKD patients is feasible with Na[18F]F PET. Na[18F]F can help to detect early changes in bone metabolism and assess the progression of bone disease in this complex condition. Quantification with Na[18F]F PET might provide better assessment of the bone turnover. The difference in Na[18F]F uptake in CKD compared to controls is likely related to a change in bone turnover which, however, requires further validation.

Prostate-Specific Membrane Antigen Expression in Metastatic Angiosarcoma Detected on 18F-PMSA PET/CT: A New Potential Prognostic Marker.

ABSTRACT: 18F-PSMA is a promising tracer for both staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the endothelium of tumor-associated neovasculature of various solid malignancies possibly due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of a 59-year-old man with known case of prostate cancer underwent 18F-PSMA for restaging. 18F-PSMA PET/CT shows multiple lytic bone lesions with high PSMA expression. Histopathological evaluation showed metastatic angiosarcoma. 18F-PSMA expression in the angiosarcoma can be potentially guided to radionuclide legend therapy.

Case of Adult Metastatic Medulloblastoma Demonstrated on 18F-DOPA PET/CT.

ABSTRACT: 18F-DOPA is a promising radiotracer used for both staging and restaging of primary brain tumors based on increased transport via the L-type large neutral amino acid transport system in tumor cells. Adult medulloblastoma is extremely rare. We present a case of 25-year-old man with posterior fossa medulloblastoma treated with surgery followed by chemotherapy and radiotherapy 5 years back, which later developed metastasis to left cerebral lobe treated with gamma knife followed by surgical debulking. Recent 18F-DOPA PET/CT demonstrates recurrence and disease progression on follow-up scan. 18F-DOPA PET/CT is extremely useful for characterizing brain tumors, response assessment, and prognosis.

Therapy-induced bone changes in oncology imaging with 18F-sodium fluoride (NaF) PET-CT.

18F-Sodium fluoride (18F-NaF) is a PET tracer that is mostly used in the evaluation of bone metastasis in oncology cases. Recently, 18F-NaF PET/CT is gaining wide popularity owing to its higher sensitivity over the other conventional bone tracer with higher and rapid single-pass extraction, negligible plasma protein binding, rapid blood, and renal clearance. In the era of constant evolution of cancer therapy regimens, considerable bone health impact is seen in the form of avascular necrosis, insufficiency fractures, among others. A significant number of these therapy-induced changes show high bone turnover and thereby 18F-NaF accumulation, mimicking metastatic lesions. This article summarizes and illustrates the pattern and morphological features of 18F-NaF PET/CT findings in these changes in the context of clinical and therapeutic history.

Incremental Value of 18F-PSMA-1007 PET/CT in Detection of Metastatic Renal Cell Carcinoma to the Brain.

ABSTRACT: 18F-PSMA PET/CT is an emerging standard of care in staging prostate cancer, evaluating biochemical recurrence and response to therapy. Despite the nomenclature, PSMA expression is also documented at the tumor-associated neovasculature of other malignant solid tumors including renal cell carcinoma. We report a case of 44-year-old man known to have renal cell carcinoma who underwent 18F-PSMA and 18F-FDG PET/CT for restaging after radical nephrectomy. A well-defined solitary cerebellar lesion with marked PSMA expression and equivocal FDG uptake was noted. MRI brain confirmed a matching cerebellar metastatic lesion. 18F-PSMA expression in the metastatic RCC raises a prospective guide to futuristic theragnostic uses.

18F-PSMA-1007 Uptake in Paget Disease of the Bone: An "Iron Man" Sign.

ABSTRACT: 18F-PSMA is a promising tracer for both staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the benign pathological conditions. We report a case of 81-year-old man with a known case of prostate cancer who underwent 18F-PSMA for restaging. 18F-PSMA PET/CT shows intense tracer uptake in the frontal bone appearing like an "Iron Man" sign. Corresponding noncontrast CT images, pagetoid changes with thickened cortex, mixed lytic/sclerotic mottled pattern. It is important to recognize 18F-PSMA expression in the benign nonprostatic pathologies to avoid false interpretation.

Incremental diagnostic value and impact on patient management of somatostatin receptor scintigraphy with indium-111-pentetreotide in gastroenteropancreatic neuroendocrine tumors.

OBJECTIVE: To evaluate the efficacy of somatostatin analog scintigraphy with indium-111-pentetreotide and its overall impact on management in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET). SUBJECTS AND METHODS: Twenty-two consecutive patients with a proven or clinically suspected GEP-NET with or without proven metastases were imaged at 24 and 48 h after injection of (111)In-pentetreotide. The scintigraphic findings were compared with results from conventional imaging methods. The final diagnosis was based on histopathological and surgical findings and complementary radiology. RESULTS: Somatostatin receptor-positive lesions were found in 20 of the patients, whereas conventional methods were positive in 18 patients. Additionally, 13 new tumor sites were discovered by somatostatin receptor scintigraphy in 5 patients (liver: 6; chest: 2; bone: 1; abdomen: 4). The surgical therapeutic strategy was changed in 7 patients (32%). CONCLUSIONS: Our data reinforced that scintigraphy with (111)In-pentetreotide represents the imaging modality of choice in the initial evaluation of GEP-NET. It is highly accurate and can identify clinically unsuspected lesions and optimize the overall staging. It also guides optimal therapy choice and most importantly identifies patients with inoperable or metastatic disease who might be candidates for high-dose targeted therapy.

18F-PSMA-1007 PET/CT for Initial Staging of Renal Cell Carcinoma in an End-Stage Renal Disease Patient.

A 46-year-old man with end-stage renal disease and renal cell carcinoma underwent F-FDG PET/CT for initial staging followed by F-PSMA-1007 PET/CT. Unlike F-FDG, which undergoes renal clearance, F-PSMA-1007 undergoes hepatobiliary clearance and thus generates superior quality images. F-PSMA-1007 PET/CT showed intense tracer-avid left renal mass lesion (FDG nonavid); lytic bone lesions (FDG avid) and single liver lesion (FDG nonavid). This case highlights the superiority of F-PSMA-1007 over F-FDG PET/CT in identifying primary lesion as well as metastatic sites in case of renal cell carcinoma even in the presence of end-stage renal disease.

The clinical effectiveness of reconstructing 18F-sodium fluoride PET/CT bone using Bayesian penalized likelihood algorithm for evaluation of metastatic bone disease in obese patients.

OBJECTIVE: A new Bayesian penalized likelihood reconstruction algorithm for positron emission tomography (PET) (Q.Clear) is now in clinical use for fludeoxyglucose (FDG) PET/CT. However, experience with non-FDG tracers and in special patient populations is limited. This pilot study aims to compare Q.Clear to standard PET reconstructions for 18F sodium fluoride (18F-NaF) PET in obese patients. METHODS: 30 whole body 18F-NaF PET/CT scans (10 patients with BMI 30-40 Kg/m2 and 20 patients with BMI >40 Kg/m2) and a NEMA image quality phantom scans were analyzed using ordered subset expectation maximization (OSEM) and Q.Clear reconstructions methods with B400, 600, 800 and 1000. The images were assessed for overall image quality (IQ), noise level, background soft tissue, and lesion detectability, contrast recovery (CR), background variability (BV) and contrast-to-noise ratio (CNR) for both algorithms. RESULTS: CNR for clinical cases was higher for Q.Clear than OSEM (p < 0.05). Mean CNR for OSEM was (21.62 ± 8.9), and for Q.Clear B400 (31.82 ± 14.6), B600 (35.54 ± 14.9), B800 (39.81 ± 16.1), and B1000 (40.9 ± 17.8). As the ß value increased the CNR increased in all clinical cases. B600 was the preferred ß value for reconstruction in obese patients. The phantom study showed Q.Clear reconstructions gave lower CR and lower BV than OSEM. The CNR for all spheres was significantly higher for Q.Clear (independent of ß) than OSEM (p < 0.05), suggesting superiority of Q.Clear. CONCLUSION: This pilot clinical study shows that Q.Clear reconstruction algorithm improves overall IQ of 18F-NaF PET in obese patients. Our clinical and phantom measurement results demonstrate improved CNR and reduced BV when using Q.Clear. A ß value of 600 is preferred for reconstructing 18F-NaF PET/CT with Q.Clear in obese patients. ADVANCES IN KNOWLEDGE: 18F-NaF PET/CT is less susceptible to artifacts induced by body habitus. Bayesian penalized likelihood reconstruction with18F-NaF PET improves overall IQ in obese patients.

Baseline patterns of bone scintigraphy in patients with established post-poliomyelitis paralysis.

INTRODUCTION: Post-poliomyelitis syndrome causes variable musculoskeletal manifestations including pain, muscle weakness and fatigue. These manifestations are commonly secondary to overuse and misuse of muscles and joints and could follow a fall. Bone scan can be useful in determining the underlying cause and follow-up. The objective of this study was to describe the late scintigraphic patterns on bone scan following poliomyelitis. MATERIALS AND METHODS: Bone scans of 8 adult patients (7 female and 1 male), aged 35 to 53 years, who were known to have paralytic poliomyelitis, were retrospectively studied. Six patients had unilateral while 1 had bilateral disease. All patients had three-phase bone scan and 5 had SPECT study as well. Studies were reviewed by two qualified nuclear medicine physicians and findings were recorded and analyzed. RESULTS: Several patterns were consistently identified: decreased blood pool activity in the affected lower limb of all patients; deformed ipsilateral hemi-pelvis with reduced uptake on the affected side in all patients with unilateral disease; stress changes with increased uptake in the bones of the contra-lateral lower extremity; and degenerative changes in multiple joints (shoulder, knee, hip, ankle and spine). Significant scoliosis was only noted in the patient with bilateral disease. CONCLUSION: Scintigraphic patterns on bone scan associated with the post-poliomyelitis syndrome and persistent weakness following a distant episode of poliomyelitis have been described. Awareness of these characteristic scintigraphic findings may facilitate an accurate diagnosis and lead to more appropriate patient management.

Evaluation of the gamma probe guided sentinel lymph node biopsy and the blue dye technique in the management of breast cancer.

The aim of this study was to evaluate the efficacy of lymphoscintigraphy, gamma probe guided sentinel lymph node biopsy (GP-SLNB) in the management of breast cancer and study the follow-up results. Fifty two patients (mean age 47.28+/-9.7; range 23-69yr) with operable breast carcinoma and clinically negative axilla were studied. Scintigraphy for the detection of SLN was performed 2-4h before surgery by injecting technetium-99m labeled nanocolloid intradermally in the peritumoral region. First lymph node (LN) to appear on the scan was labeled as SLN and by using the GP was marked on the skin. Blue dye was also injected in all patients intraoperatively and hot and/or blue LN were studied in the axilla using the GP. The SLN was identified in 50 patients (96% success rate) while in 2 patients SLN was not visualized on imaging. The blue dye successfully localized SLN in 45/52 (87%) of the cases. Of the 52 patients, 16 had axillary lymph node dissection (ALND), including 14 SLNB positive for lymph node metastases cases and the two cases in which no SLN was imaged. In the remaining 36/52 cases SLN were negative for metastases and patients on the follow-up remained disease free (NPV 100% for a follow-up period of 12-36 months). The success rate, sensitivity, negative predictive value, and accuracy were 96%, 93%, 100%, and 98% using the GP-SLNB, 87%, 80%, 100%, and 93% using blue dye, and 98%, 100%, 100%, and 98% using combined methods, respectively. In conclusion, lymphoscintigraphy, GP-SLNB has a higher success rate and sensitivity versus the dye technique and when combined with the blue dye technique its sensitivity increases to 100%. We found a high negative predictive value for SLNB and the recurrence rate in these negative SLNB was comparable to the ALND.

18F-PSMA 1007 Uptake in a Man With Metastatic Breast Cancer.

A 72-year-old man, who is known with a case of metastatic carcinoma of the breast, was referred for F-PMSA 1007 PET/CT with clinical suspicion of synchronous prostate cancer. F-PSMA 1007 PET/CT scan detected no abnormal tracer concentrating lesion in the prostate gland; however, abnormal tracer concentration was noted in soft tissue lesions in left breast, metastatic lymph nodes, and skeletal lesions. Compared with F-FDG PET/CT, more bone lesions were detected on F-PSMA 1007 imaging. The findings of our case open the possibility of imaging metastatic breast cancer with F-PSMA 1007 in men.

18F-PSMA 1007 Brain PET/CT Imaging in Glioma Recurrence.

A 64-year-old man with a known case of right parietal lobe glioblastoma multiforme operated on in August 2018 was referred for F-FDG PET/CT with a clinical suspicion of recurrence. He underwent F-FDG and F-PSMA 1007 scans. Both the scans showed intense tracer uptake in right parietal lobe lesion, which concurred with MRI findings of recurrent disease and was later proven on histopathologic examination as recurrence. Our case highlights the feasibility of F-PSMA 1007 PET/CT imaging of suspected glioblastoma recurrence. Considering its similarity to PSMA-617, it may be used as a surrogate imaging tracer for potential theranostic application using alpha or beta emitters.

18F-PSMA 1007 Uptake in Brain Metastases From Breast Cancer.

A 64-year-old woman with metastatic breast cancer on follow-up had suspicious recurrent brain metastases. She underwent F-FDG PET/CT, F-PSMA 1007 brain PET/CT, and brain MRI. F-PSMA 1007 showed intense tracer localization in the suspected recurrent brain metastasis in right parietal lobe and also picked up 2 more metastatic brain lesions, which had concurrent findings of metastasis in subsequent MRI. Our case highlights the feasibility of F-PSMA 1007 PET/CT imaging of brain metastases from nonprostate cancers. It may be used as surrogate imaging tracer for potential theranostic application using alpha or beta emitters considering its similarity to PSMA-617.