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Fibroblast activation protein (FAP) is a type-II membrane bound glycoprotein specifically expressed by activated fibroblasts almost exclusively in pathological conditions including arthritis, fibrosis and cancer. FAP is overexpressed in cancer-associated fibroblasts (CAFs) located in tumor stroma, and is known to be involved in a variety of tumor-promoting activities such as angiogenesis, proliferation, resistance to chemotherapy, extracellular matrix remodeling and immunosuppression. In most cancer types, higher FAP expression is associated with worse clinical outcomes, leading to the hypothesis that FAP activity is involved in cancer development, cancer cell migration, and cancer spread. Recently, various high selectivity FAP inhibitors (FAPIs) have been developed and subsequently used for positron emission tomography (PET) imaging of different pathologies. Considering the paucity of widely available and especially mainstream reliable radioligands in brain cancer PET imaging, and the poor survival rates of patients with certain types of brain cancer such as glioblastoma, FAPI-PET represents a major development in enabling the detection of small primary or metastatic lesions in the brain due to its biological characteristics and low background accumulation. In this work, we aim to summarize the potential avenues for use of FAPI-PET, from the basic biological processes to oncologic imaging and with a main focus on brain imaging., Competing Interests: JD is an employee of Siemens Medical Solutions who did not financially sponsor this work. The author(s) OB declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Djekidel, Alsadi, Abi Akl, Bouhali and O' Doherty.)

Nuclear Medicine is witnessing a revolution across a large spectrum of patient care applications, hardware, software and novel radiopharmaceuticals. We propose to offer a framework of the nuclear medicine practice of the future that incorporates multiple novelties and coined as the NEW (nu) Clear medicine. All these new developments offer a significant clarity and real clinical impact, and we need a concerted effort from all stakeholders in the field for bedside implementation and success., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Djekidel.)

68 Ga-DOTATATE PET/CT is widely used for the evaluation of neuroendocrine tumors. Some reports exist on its use in the management of neuroblastoma. Building on the prior reports as well as our previous experience in using this technique for initial staging, we propose to describe its practical benefits in restaging and response to therapy. We describe different aspects including supply logistics, preparation, spatial resolution, and other practical applications. Methods: We reviewed the medical records for 8 patients who were evaluated with 68 Ga-DOTATATE PET/CT at our institution over 2 y. A note was made of the patient and disease characteristics and the indication for PET imaging, and the results were retrospectively analyzed for feasibility, logistics, radiation exposure, and utility in answering the clinical question. Results: Eight children (5 girls and 3 boys; age range, 4-60 mo; median age, 30 mo) diagnosed with neuroblastoma were imaged with 68 Ga-DOTATATE PET/CT and 5 with 123 I-metaiodobenzylguanidine ( 123 I-MIBG) SPECT/CT over 2 y. Three 68 Ga-DOTATATE PET scans were done for staging, 10 for response evaluation, and 2 for restaging. 68 Ga-DOTATATE PET accurately identified neuroblastoma lesions suspected or seen on anatomic imaging. It has been shown to be more specific and more sensitive than 123 I-MIBG and at times also MRI. It had better spatial and contrast resolution than 123 I-MIBG. 68 Ga-DOTATATE PET was better than 123 I-MIBG SPECT/CT, CT, and MRI in the detection of early progression and viable tumor delineation for response assessment, as well as in target volume definition for external-beam radiotherapy and proton-beam radiotherapy. 68 Ga-DOTATATE PET was also better at assessing bony and bone marrow disease changes with time. Conclusion: 68 Ga-DOTATATE PET/CT offers added value and a superior edge to other imaging modalities in restaging and response assessment in neuroblastoma patients. Further multicenter evaluations in larger cohorts are needed., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The terms "renal regenerating nodule" and "nodular compensatory hypertrophy" are used in the literature to describe functioning pseudo-tumors (FPT) in the setting of an extensively scarred kidney. FPTs are usually discovered incidentally during routine renal imaging. Differentiating these FPTs from renal neoplasms is critical but can be challenging in the setting of chronic kidney disease (CKD) given the limitations related to using contrast-based imaging., Case Summaries: We report a pediatric case series of 5 CKD patients, with history of urinary tract infections, in which tumor-like lesions evolved in scarred kidneys and were incidentally discovered on routine renal imaging. These were diagnosed as FPT by utilizing dimercaptosuccinic acid (DMSA) imaging and showed stable size and appearance upon follow-up with ultrasound and MRI., Conclusion: FPTs can be picked up on routine imaging of pediatric patients with CKD. Although larger cohort studies are needed to confirm these conclusions, our case series supports the evidence that DMSA scan showing uptake at the site of the mass can be a useful tool to suggest the diagnosis of FPTs in children with kidney scarring, and that SPECT DMSA scan adds more precision in picking up and accurately localizing FPTs compared to planar DMSA., (© 2023. The Author(s).)

Background: Prostate specific membrane antigen (PSMA) ligand labeled with Lutetium-177 (177Lu) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCRPC). Several prospective and retrospective studies as well as clinical trials are completed or underway. This has ultimately led to the approval of this therapy by the US Food and Drug Administration (FDA) on March 23 2022. Our work aims to present a mini-review of the most recent research performed and the potential future directions of 177Lu-PSMA-radioligand therapy (RLT) for mCRPC patients., Main Body: For patients with mCRPCwho have met the eligibility criteria for 177Lu-PSMA RLT, numerous studies and trials are either ongoing or have been completed. The studies included in this review have reported overall biochemical response, defined as a prostate-specific antigen (PSA) decline of at least 50%, in at least 44% of patients with mCRPC. The median ranges of overall survival (OS) and radiographic progression-free survival (rPFS) were reported within 10.7-56 and 3.6-16 months, respectively. With data from several retrospective and prospective studies published, the safety of 177Lu-PSMA RLT in mCRPC has been confirmed and demonstrated by its low toxicity profile. Various studies have published pharmacokinetic/pharmacodynamic models to better understand the absorption, distribution, metabolism, and excretion of the RLT in this patient population. Findings have been published for 177Lu-PSMA RLT alone and in combination with other agents. We summarize their findings in our review., Conclusions: The efficacy of 177Lu-PSMA RLT for patients with mCRPC has been proven thus far with promising results: PSA response, OS and rPFS when used alone or in combination with other treatment options, relative to the standard treatment options alone. The low toxicity profile noted also proves the safety of 177Lu-PSMA RLT in these patients., (© The Author(s) 2022. Published by Oxford University Press.)

18 F-FDG PET plays a major role in the pre-surgical evaluation of medically refractory epilepsy patients. The current standard of care is performing interictal evaluations of glucose metabolism. This is mostly related to the tracer kinetics of 18 F-FDG owing to a long uptake phase which would translate into ictal injections having low sensitivities and low specificity and demonstrating not only ictal but post-ictal changes. It has been reported that this limitation can be overcome in some status epilepticus scenarios where prolonged seizures can then correlate better with 18 F-FDG uptake kinetics. In these cases, focal visual qualitative hot spots are suggestive of the seizure onset zone (SOZ). However, we note that by using advanced subtraction techniques, the prolonged 18 F-FDG uptake phase can be overcome in a variety of other cases as well. This opens the door to a slightly larger set of patients that may benefit from this higher resolution PET method. We present 4 cases where a novel subtraction 18 F-FDG PET technique was used and elucidate its impact in these specific cases., (Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Although MRI is the workhorse of brain tumor initial evaluation and follow-up, there is a growing amount of data recommending the incorporation of amino-acid PET imaging at different stages of the management of these patients. Recent nuclear medicine and neuro-oncology clinical practice recommendations support the use of amino-acid imaging in brain tumor imaging. Considering 18 F-DOPA is FDA approved for the evaluation of parkinsonian syndromes, it could be used clinically for other valuable clinical indications such as brain tumor evaluations. This value seems to be well established in adults and has growing evidence for its use in pediatrics as well. We offer to present four pediatric brain tumor cases imaged with 18 F-DOPA and review the literature., (Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Splenosis, commonly occurs incidentally and locates to bowel surfaces, parietal peritoneum, mesentery, and diaphragm, but can potentially occur anywhere in the peritoneal cavity. Patients frequently have a history of splenectomy or trauma. On the other hand, hepatic splenosis is a rare entity and may present itself clinically. Indeterminate liver lesions can pose a clinical dilemma and may lead to additional investigations, anxiety, follow-up imaging and even to invasive procedures. MRI usually performs extremely well. In difficult cases, scintigraphy can be of great value -especially with novel SPECT-CT and SPECT-MR techniques-. We describe a case of a 29-year-old lady with hepatic splenosis and the impact of hybrid imaging., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: Radioactive iodine (RAI) is used to treat thyroid cancer patients with a clear paradigm for most patients. End-stage renal disease (ESRD) patients pose several challenges when undergoing RAI treatment, primarily due to the lack of renal clearance. We retrospectively report our experience with RAI treatment in a cohort of patients with ESRD and provide a set of recommendations on aspects such as the need for adjusted dose activity, balancing scheduling between RAI therapy and dialysis, and radiation safety precautions., Patients and Methods: In this study, we report on 5 patients (6 cases), with ESRD on dialysis, treated with RAI for thyroid cancer. Retention measurements to determine individual biological clearance of RAI from the patient's body before and after dialysis sessions were assessed using external exposure dose rates measured at 1 m., Results: Delayed biological clearance of RAI, after the first hemodialysis session, resulted in a longer RAI effective half-life as a consequence of longer retention periods, consistent with observations reported in scientific literature. To achieve a much closer radiation exposure compared with a nondialysis patient, one would recommend administering ~20%-30% of the dose activity normally administered to a thyroid cancer patient based on their medical history, histopathology, and uptake with the appropriate dialysis schedule., Conclusions: Special precautions should be taken with the administration of RAI in ESRD patients by adjusting the prescribed dose activity, dialysis sessions, and paying special attention to wastes. Pooling data from multiple centers may be useful to build a consensus and substantiated recommendations., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Lung cancer is the number 1 cause of cancer deaths in the United States. The prognosis is quite grim with the exception of stage 1. When faced with several failed therapeutic regimens and rapid progression of the disease, considering alternative therapies such as radiopharmaceutical therapies may be an option. We describe the case of a 36-y-old man with lung adenocarcinoma who had imaging molecular characterization of his disease with 18 F-FDG, 68 Ga-DOTATATE, and 18 F-fluoride PET/CT scans that were able to shed some light on molecular characterization of his disease and serve as a guide to potential targeted or personalized radiopharmaceutical therapeutic options., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Metaiodobenzylguanidine (MIBG) imaging has been the standard for neuroblastoma staging for many decades. Novel agents such as 18 F-DOPA and 68 Ga-DOTATATE are being used nowadays in academic centers. During the coronavirus disease 2019 (COVID-19) pandemic, procurement of 123 I-MIBG has proved particularly challenging, necessitating the use of 68 Ga-DOTATATE PET. 68 Ga-DOTATATE is Food and Drug Administration-approved for imaging of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Methods: 68 Ga-DOTATATE PET/CT imaging was performed for staging of 3 pediatric patients with neuroblastoma at our institution. A review of the literature was also completed. Results: 68 Ga-DOTATATE PET/CT scans were successfully performed on all patients. All patients showed 68 Ga-DOTATATE-avid disease. PET scans showed an excellent spatial resolution and demonstrated high accuracy in concordance with current European Association of Nuclear Medicine guidelines. Conclusion: We have presented 68 Ga-DOTATATE PET/CT imaging for staging of neuroblastoma and believe it can reliably be used as an alternative to 123 I-MIBG. It has technical, clinical, and practical advantages making it an attractive option. Further multicenter studies are required before it can be recommended for standard clinical use., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Congenital hyperinsulinism (CHI) occurs most commonly in infants but may also be discovered in older children. It presents with recurrent episodes of hypoglycemia due to high endogenous insulin levels. There is a focal and diffuse form of the disease depending on the extent of pancreatic involvement. Hyperplasia of the islet cells results in hyperfunctioning pancreatic β cells and the ensuing clinical disease. Medical treatment fails in several patients and surgery has been shown to be very effective in improving prognosis and even resolution of disease in the focal form. Several genetic mutations have been uncovered and these may also be predictive of prognosis. Anatomical imaging alone including ultrasound, CT and MRI are rarely able to detect any abnormality in the pancreas. PET plays a major role in the distinction between the focal and diffuse forms of the disease. It also guides surgical intervention by providing information on the location of the focal hyperfunctioning islet cells. Imaging children and infants in this disease is quite challenging. We propose to show the benefit of using two PET tracers in this disease. 18 F-FDOPA has been used quite successfully in the evaluation of CHI. 68 Ga-DOTATATE has also been described to be helpful although inferior to 18 F-FDOPA. We illustrate imaging of CHI patients in 3 different scans and briefly review the literature. 18 F-FDOPA as described in the literature is superior but when unavailable 68 Ga-DOTATATE may be a reasonable alternative., Competing Interests: None., (AJNMMI Copyright © 2021.)

18 F-FDG PET scans have proven to be useful in the diagnosis and management of encephalitis patients. 18 F-FDG PET scans are also the standard of care in the evaluation of epilepsy patients before surgery. Encephalitis patients who later develop epilepsy may have useful imaging findings at the time of diagnosis. We present a case of 18 F-FDG PET imaging in a patient with recurrent cryptogenic meningoencephalitis. 18 F-FDG PET imaging after resolution of the encephalitis revealed hypometabolism in previously hypermetabolic areas. Hence, the initial 18 F-FDG PET scan prospectively predicted the epileptogenic zone and seizure-onset zone., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

The human epidermal growth factor 2 (HER2)-overexpressing (HER2-positive [HER2+]) gastric (GC) and gastroesophageal junction adenocarcinomas (GEJC) are felt to represent a more aggressive form of disease, which may correlate to increased metabolic activity. Whether tumor SUV max measured by 18 F-FDG PET/CT could be a preoperative parameter used to predict HER2 status of GC/GEJC is unknown., Methods: Pathology reports of HER2+ GC/GEJC biopsies and resections from 31 patients were reviewed and compared with HER2-negative (HER2-) cases distributed evenly over the same time period. We analyzed their SUV max intensity and then compared the HER2 status and SUV max parameters and their association with survival., Results: After matching for age and sex, there was no difference in SUV max between HER2+ and HER2- cases (9.7 and 8.4, respectively; P = 0.6). No difference was seen between HER2+ and HER2- cases in tumor histology (81% and 57% intestinal type, respectively; P = 0.11), size (2.6 and 3.8 cm, respectively; P = 0.12), differentiation (47% and 68% poorly differentiated, respectively; P = 0.06), or presence of lymph node metastasis (60% and 40%, respectively; P = 0.3). Although there was no difference in survival demonstrated by HER2+ and HER2- cases, there was a significant difference in survival between SUV max above (12.2 mo) and below (30 mo) the median SUV max (6.6, P = 0.01)., Conclusion: Our study shows that SUV max is not associated with HER2 status of GC/GEJC. Independent of HER2 overexpression, patients with a high SUV max demonstrate a worse overall survival, suggesting that metabolic signature is a better predictor of biologic tumor aggressiveness than its histologic signature., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

(18)F Fluorodeoxyglucose (FDG) positron emission tomography (PET) scans are performed routinely for oncologic patients. Myocardial uptake can vary among patients and between serial studies in the same patient. Our study aims to evaluate myocardial metabolism on staging FDG PET scans and to analyze factors influencing patterns of cardiac uptake, and their relevance. We analyzed retrospectively 100 PET-CT scans from 20 fasting lymphoma patients. Distribution of myocardial uptake was determined by visual assessment and the maximum standardized uptake value (SUVm) was calculated. Multiple variables were analyzed including: fasting length, cardiovascular risk factors, SUVm, and location of uptake. We found no correlation between fasting hours and cardiac uptake (p-value: 0.4786). There was a trend that showed less uptake in patients scanned in the afternoon versus the morning, although this was not statistically significant. The location of maximum uptake was unexpectedly variable in several patients and could not be ascertained to a specific cause. Interestingly, we found no correlation between cardiac risk factors and the amount of myocardial uptake. Myocardial FDG uptake is spatially and temporally heterogeneous. Differences in myocardial wall pattern and peak uptake exist and may not be explained by the length of fasting, gender, age or cardiac risk factors. This variability may occur in daily cardiac evaluations and affect interpretations of sarcoidosis and viability studies and should be further explored. A larger cohort study is necessary to confirm that our findings do not confer a higher cardiac risk profile to the cancer patient.

Background: This retrospective study assessed the effect of the addition of SPECT/CT imaging on the diagnostic accuracy of labeled leukocyte scintigraphy., Methods: Leukocyte scans of 134 patients performed between December 2005 and December 2009 were reviewed. All patients underwent whole-body planar and SPECT/CT imaging with either (111)In-oxine- or Tc-99m-hexamethylpropylene amine oxime (HMPAO)-labeled leukocytes. Leukocyte imaging identified a total of 221 lesions. Based on additional diagnostic tests and clinical follow-up, a final diagnosis was established in 115 patients., Results: A total of 113 focal lesions with an established final diagnosis were detected on imaging in bone (n = 43), soft-tissues (n = 34), vascular grafts (n = 19), and other surgical implants (n = 17), whereas 26 scans resulted negative. Overall, leukocyte scanning including SPECT/CT yielded sensitivity, specificity, positive and negative predictive values of 87.5%, 85.3%, 83.6%, and 88.9%, respectively. As compared to planar imaging and SPECT, SPECT/CT imaging significantly increased the number of correctly identified lesion locations and improved overall reader confidence in 77 (68%) and 71 (63%) of 113 focal lesions, respectively (P < 0.001). Significant differences in scan accuracy were neither observed between In-oxine- or Tc-99m-hexamethylpropylene amine oxime-labeled leukocyte studies, nor between scans obtained with or without antibiotic treatment., Conclusions: Hybrid SPECT/CT leukocyte imaging has incremental value over planar imaging with SPECT because of improved diagnostic accuracy of lesion identification and reader confidence.

Background: In general, thyroid carcinomas, when they behave aggressively, metastasize to lungs and occasionally to bone and brain. Metastases to other organs are distinctly unusual. Renal metastases have been reported in only 10 patients. Here we report, to the best of our knowledge, the first patient with Hurthle cell thyroid cancer and renal metastasis. The evaluation of this patient was enhanced by utilizing a variety of imaging techniques., Summary: The patient was a 75-year-old man who had a history of a total thyroidectomy 9 years previously for a right thyroid lobe Hurthle cell carcinoma. He postoperatively received 150 mCi (5550 MBq) of 131-I therapy and was maintained on thyrotropin suppressive therapy with levothyroxine. He presented to us with a recent history of a progressively enlarging left neck mass. The serum thyroglobulin was elevated to 1183 ng/mL. Multimodality imaging with fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance imaging, and Somatostatin receptor scintigraphy with single photon emission computed tomography (SPECT)-computed tomography revealed numerous foci in the skeleton and right kidney. Anatomic imaging characteristics favored a primary renal cell cancer with the additional evidence of renal vein invasion and thrombosis. Histology later revealed a metastatic renal Hurthle cell cancer with positive thyroglobulin stains. Several of the skeletal foci responded partially to cryoablative therapy. The patient refused noncurative Somatostatin analog therapy. He is alive and doing well clinically., Conclusion: The management of thyroid cancers in high-risk groups, such as our patient, frequently requires expert management by the use of novel multimodality imaging and therapeutic techniques.

The incidental discovery of adrenal masses during modern diagnostic imaging is a common occurrence. These masses form part of a long differential diagnostic list; most often, they are benign adrenal adenomas, but their discovery requires a clinical evaluation that is sufficiently broad to exclude clinically silent endocrine disease, metastases to the adrenal gland in patients with suspected or known malignancies, and rare adrenocortical carcinomas. CT, MRI and nuclear medicine approaches have all been used to evaluate incidentally discovered adrenal masses. Each technology provides information that contributes to the noninvasive characterization of the majority of these neoplasms. Understanding of the modalities used to assess an unanticipated adrenal mass allows for more rapid diagnosis and cost avoidance in a condition that has been referred to as a 'disease' of modern imaging technology.

Scintigraphy has historically added much to the evaluation of adrenal dysfunction and tumor localization. The early development of radiopharmaceuticals for adrenocortical imaging provided vital clinical information well before the widespread availability of computed tomography (CT), but beginning in the early 1980's nuclear imaging became supplanted in large part by high resolution CT and more recently by magnetic resonance imaging. The parallel emergence of radiopharmaceuticals for adrenomedullary imaging also provided important functional insight in evaluating these neoplasms, but despite the clinical value of such nuclear probes they too, were relegated to a less prominent role in tumor characterization because of advances in anatomic imaging. However, with the recent introduction of dual-modality imaging platforms that directly combine CT with scintigraphy, either as single photon emission tomography (SPECT)/CT or positron emission tomography (PET)/CT, nuclear medicine studies once again play an integral role in adrenal tumor evaluation.

Foot drop can be defined as a significant weakness in ankle and toe dorsiflexion. Injury to the dorsiflexors or to any point along the neural pathways that supply these muscles can result in a foot drop. Injury to the peroneal nerve is usually the major precipitant. Other causes vary from trauma to surgical nerve injury, as well as leg compartment syndromes or dorsiflexor injuries, peripheral nerve injuries, stroke, neuropathies, drug toxicities, spinal stenosis, L5 sciaticas, systemic diseases such as connective tissue diseases, vasculidities, or diabetes. This report focuses on a patient presenting with a foot drop as an unusual manifestation of brain metastasis. His minimal symptomatology seemed to point towards a local process. Therefore, early recognition and prompt treatment are essential. The central nervous system must be the target of investigations when the workup fails to disclose the proper etiology. Potential diagnostic delays may occur. Certain cases may require a more aggressive approach.