Adult Neuroblastoma of the Neck Is Better Imaged With 18 F-FDG PET/CT Than With 18 F-DOPA PET/CT.

ABSTRACT: A 41-year-old woman presented with 2 months history of right submandibular swelling. Biopsy revealed neuroblastoma (NB). Patient was referred for staging PET/CT scan. We compared the findings of 18 F-DOPA PET/CT and 18 F-FDG PET/CT scans. Both imaging modalities were positive in the patient; however, tumor delineation was superior with 18 F-FDG PET/CT. Tumor uptake of FDG was significantly higher than tumor uptake of DOPA. Follow-up FDG PET/CT scan postsurgery showed local recurrent NB and their metastases avidly concentrate FDG. We present a very rare case of adult NB of the neck better imaged with FDG instead of DOPA PET/CT.

68Ga-DOTATATE PET/CT Incidentally Detects Relapsed Chronic Lymphocytic Leukemia in Patient With Metastatic Neuroendocrine Tumor.

ABSTRACT: A 54-year-old man with metastatic well-differentiated neuroendocrine tumor of the pancreas underwent 68Ga-DOTATATE PET/CT scan to evaluate treatment response. Patient was known for remote history of chronic lymphocytic leukemia (CLL), previously treated. Scan revealed diffusely increased abnormal tracer uptake throughout the marrow of the axial and proximal appendicular skeleton. Bone marrow biopsy revealed relapsed CLL. We present a rare case of relapsed CLL incidentally detected on 68Ga-DOTATATE PET/CT.

Altered Glucose Metabolism Postchemotherapy Precedes PSMA Expression in Poorly Differentiated Prostate Cancer.

ABSTRACT: A 73-year-old man presented with gastric lesion on upper endoscopy, biopsy-proven as poorly differentiated carcinoma. Staging FDG PET/CT scan showed gastric, intraprostatic, nodal, and extensive osseous lesions. Prostate-specific antigen levels were greater than 1000. The patient was treated as metastatic poorly differentiated prostate cancer with chemotherapy. Posttherapy 18 F-PSMA-1007 and FDG PET/CT scans were obtained. PSMA PET/CT scan revealed extensive disease similar in appearance as staging FDG PET/CT scan, indicating no apparent treatment response. FDG PET/CT scan showed partial metabolic response, correlating with improved prostate-specific antigen levels. This case indicates that chemotherapy-induced changes in glucose metabolism likely precede change in PSMA expression in poorly differentiated prostate cancer.

FDG PET/CT in Initial Staging of Adult Soft-Tissue Sarcoma.

Soft-tissue sarcomas spread predominantly to the lung and it is unclear how often FDG-PET scans will detect metastases not already obvious by chest CT scan or clinical examination. Adult limb and body wall soft-tissue sarcoma cases were identified retrospectively. Ewing's sarcoma, rhabdomyosarcoma, GIST, desmoid tumors, visceral tumors, bone tumors, and retroperitoneal sarcomas were excluded as were patients imaged for followup, response assessment, or recurrence. All patients had a diagnostic chest CT scan. 109 patients met these criteria, 87% of which had intermediate or high-grade tumors. The most common pathological diagnoses were leiomyosarcoma (17%), liposarcoma (17%), and undifferentiated or pleomorphic sarcoma (16%). 98% of previously unresected primary tumors were FDG avid. PET scans were negative for distant disease in 91/109 cases. The negative predictive value was 89%. Fourteen PET scans were positive. Of these, 6 patients were already known to have metastases, 3 were false positives, and 5 represented new findings of metastasis (positive predictive value 79%). In total, 5 patients were upstaged by FDG-PET (4.5%). Although PET scans may be of use in specific circumstances, routine use of FDG PET imaging as part of the initial staging of soft-tissue sarcomas was unlikely to alter management in our series.

GSK3 beta regulates myelin-dependent axon outgrowth inhibition through CRMP4.

Myelin-associated inhibitors (MAIs) contribute to failed regeneration in the CNS. The intracellular signaling pathways through which MAIs block axonal repair remain largely unknown. Here, we report that the kinase GSK3beta is directly phosphorylated and inactivated by MAIs, consequently regulating protein-protein interactions that are critical for myelin-dependent inhibition. Inhibition of GSK3beta mimics the neurite outgrowth inhibitory effect of myelin. The inhibitory effects of GSK3beta inhibitors and myelin are not additive indicating that GSK3beta is a major effector of MAIs. Consistent with this, overexpression of GSK3beta attenuates myelin inhibition. MAI-dependent phosphorylation and inactivation of GSK3beta regulate phosphorylation of CRMP4, a cytosolic regulator of myelin inhibition, and its ability to complex with RhoA. Introduction of a CRMP4 antagonist attenuates the neurite outgrowth inhibitory properties of GSK3beta inhibitors. We describe the first example of GSK3beta inactivation in response to inhibitory ligands and link the neurite outgrowth inhibitory effects of GSK3beta inhibition directly to CRMP4. These findings raise the possibility that GSK3beta inhibition will not effectively promote long-distance CNS regeneration following trauma such as spinal cord injury.

Altered hepatic metabolic activity in patients with hepatic steatosis on FDG PET/CT.

OBJECTIVE: FDG PET studies frequently use the liver as an internal reference organ to assess the significance of FDG uptake in pathologic processes involving other organs. The purpose of this study was to assess whether hepatic steatosis has a significant effect on the standardized uptake value (SUV) of the liver. SUBJECTS AND METHODS: This prospective case-control study analyzed FDG PET/CT scans of patients with frank hepatic steatosis on the unenhanced CT portion of the study. Maximum SUVs (corrected for both body weight [SUV(bw)] and lean body mass [SUV(lbm)]) in 37 patients with hepatic steatosis were compared with those in 37 control patients without hepatic steatosis. RESULTS: Patients with hepatic steatosis had statistically significant smaller mean (± SD) values than did the control subjects for liver SUV(lbm) (1.91 ± 0.57 vs 2.17 ± 0.36), liver SUV(lbm)-mediastinum ratio (1.23 ± 0.19 vs 1.35 ± 0.19), and liver SUV(bw)-mediastinum ratio (1.24 ± 0.16 vs 1.39 ± 0.22). CONCLUSION: Hepatic steatosis results in a small statistically significant decrease in hepatic metabolic activity, as measured by FDG PET. However, because the degree of change is small, compared with healthy control subjects, this decrease is unlikely to have any clinical significance on the use of the liver as an internal reference organ.

Ductal Variant of Prostate Cancer: Serial Imaging With 18F-PSMA PET/CT.

ABSTRACT: A 51-year-old man with high-grade ductal variant of prostate cancer with normal prostate-specific antigen (PSA) levels underwent radical prostatectomy. Follow-up 18F-prostate-specific membrane antigen-targeted ligand 1007 (PSMA-1007) PET/CT revealed enlarged PSMA-expressing left common iliac node. Patient was placed on androgen deprivation therapy and was lost to follow-up. Repeat 18F-PSMA PET/CT scan after 16 months showed disease progression. PSA levels were still within normal limits. This case highlights the utility of 18F-PSMA PET/CT for staging and follow-up of patients with this rare ductal variant prostate cancer with normal PSA levels.

Multiple Solitary Plasmacytomas With Multifocal Bone Involvement Diagnosed With 68Ga-Prostate-Specific Membrane Antigen PET/CT.

A 63-year-old man with elevated prostate-specific antigen serum levels and enlarged prostate gland underwent ultrasound-guided transrectal biopsy, which did not reveal any evidence of malignancy. In order to help guidance of repeat biopsy, Ga-prostate-specific membrane antigen-targeted ligand PET (PSMA PET/CT) was ordered. PET/CT scan showed no abnormal PSMA expression within the prostate gland. There were, however, multiple PSMA-expressing osteolytic lesions throughout the axial skeleton. Bone lesion biopsy obtained for final workup revealed multiple solitary plasmacytomas with multifocal bone involvement. This rare case highlights the utility of PSMA PET/CT in diagnosing nonprostate malignancies.

Identification of CRMP4 as a convergent regulator of axon outgrowth inhibition.

Myelin-associated inhibitors (MAIs) and chondroitin sulfate proteoglycans (CSPGs) contribute to failed regeneration after neuronal injury. MAIs and CSPGs stimulate intracellular signals including the activation of RhoA and Rho kinase to block axonal extension through targeted modifications to the cytoskeleton. RhoA and ROCK are promising targets for therapeutic intervention to promote CNS repair; however, their ubiquitous expression will limit the specificity of drugs targeted to these molecules. We have identified the cytosolic phosphoprotein CRMP4b (collapsin-response mediator protein 4b) as a protein that physically and functionally interacts with RhoA to mediate neurite outgrowth inhibition. Short interfering RNA-mediated knockdown of CRMP4 promotes neurite outgrowth on myelin substrates, indicating a critical role for CRMP4 in neurite outgrowth inhibition. Disruption of CRMP4b-RhoA binding with a competitive inhibitor attenuates neurite outgrowth inhibition on myelin and aggrecan substrates. Stimulation of neuronal growth cones with Nogo leads to colocalization of CRMP4b and RhoA at discrete regions within the actin-rich central and peripheral domains of the growth cone, indicative of a potential function in cytoskeletal rearrangements during neurite outgrowth inhibition. Together, these data indicate that a RhoA-CRMP4b complex forms in response to inhibitory challenges in the growth cone environment and regulates cytoskeletal dynamics at distinct sites necessary for axon outgrowth inhibition. Competitive inhibition of CRMP4b-RhoA binding suggests a novel, highly specific therapeutic avenue for promoting regeneration after CNS injury.

Prostate Cancer Lytic Bone Metastases Imaged With 18F-Fluorocholine PET/CT.

A 76-year-old man with metastatic prostate cancer and back pain was referred for palliative radiotherapy. Staging F-fluorocholine PET/CT scan revealed fluorocholine-avid prostate mass, extensive lymphadenopathy, lung nodules, and extensive osteolytic lesions throughout the axial skeleton. Prostate cancer bone metastases are predominantly sclerotic in nature. We present F-fluorocholine PET/CT imaging of prostate cancer with very rare lytic bone metastases.

Gastrointestinal Stromal Tumor of the Prostate: Staging and Evaluation of Response to Therapy With 18F-FDG PET/CT.

A 49-year-old man presented for routine general physical examination was found with an enlarged prostate gland without associated symptoms. Ultrasound followed by computed tomography (CT) of abdomen and pelvis confirmed a markedly enlarged heterogeneous prostate gland. Subsequently, a staging flourine-18 fluorodeoxyglucose (F-FDG) positron emission tomography (PET/CT) scan revealed intensely FDG-avid mass involving the prostate, which was biopsied as gastrointestinal stromal tumor (GIST). The patient was treated with imatinib and a follow-up PET/CT scan showed complete metabolic response. F-FDG PET/CT scan is useful in staging and follow-up of this very rare extragastrointestinal stromal tumor (EGIST).

Surveillance Imaging in Patients With Endometrial Cancer in First Remission.

OBJECTIVE: The clinical benefit of surveillance imaging in endometrial cancer remains undefined. This retrospective study was conducted to evaluate the positive predictive value (PPV) of surveillance imaging in endometrial cancer. METHODS: A total of 128 patients in first remission after treatment for endometrial cancer (uterine papillary serous, clear cell, stage III endometroid) who had surveillance imaging were retrospectively identified. The surveillance period was defined from the time of first-negative scan after treatment to the time when treatment was started for recurrent disease. Reports of surveillance scans were reviewed for the presence or absence of findings. The primary outcome was PPV of surveillance imaging. Cost and radiation exposure from surveillance imaging were also evaluated. RESULTS: A total of 128 patients had 707 surveillance scans (computed tomography, positron emission tomography-computed tomography with 2-deoxy-2-[18F]fluoro-d-glucose, magnetic resonance image, and bone scans). Median follow-up was 54 months (range: 9-173). Of all, 47 patients (37%) started therapy for recurrent endometrial cancer at the discretion of the treating physician. PPV of all surveillance imaging was 57.7%. Per patient, the mean number of surveillance scans was 5.6 (range: 2-21). The mean cost of imaging was $4200 (range: $1200-$18,700) and mean radiation exposure was 109.6mSV (range: 16-445mSv). CONCLUSIONS: Surveillance imaging detected a significant number of recurrences in patients with high-risk endometrial cancer at a reasonable cost related to the overall risk. Well-designed prospective imaging trials are warranted to assess the clinical benefit of surveillance imaging.

18F-FDG PET/CT Imaging of Bilateral Renal Metastasis of Breast Adenoid Cystic Carcinoma.

We report the case of a 65-year-old woman with a history of adenoid cystic carcinoma (ACC) of the breast. Fifteen years after mastectomy, the patient underwent a right upper lobectomy for a lung mass, and biopsy indicated ACC metastasis. Ten years after lobectomy, an F-FDG PET/CT was performed for restaging to rule out further metastases. We observed intense FDG uptake in enlarged polylobulated kidneys, which was biopsy proven as ACC metastasis.

Umbilical Plugoma Mimics Melanoma Metastasis on FDG PET/CT.

An 84-year-old man with history of left forehead melanoma was found on a restaging F-FDG PET/CT scan with hypermetabolic lung nodules and a mildly FDG-avid soft tissue nodule posterior to the umbilicus. Biopsy of a right lower lobe nodule revealed metastatic melanoma. Follow-up posttreatment PET/CT scan showed complete resolution of lung nodules and unchanged FDG uptake at the level of the umbilicus. Review of the patient's medical history revealed a remote history of umbilical hernia repair. We present a case of postsurgical plugoma mimicking the appearance of melanoma metastasis on FDG PET/CT.

Pancreatitis Secondary to Anti-Programmed Death Receptor 1 Immunotherapy Diagnosed by FDG PET/CT.

A 57-year-old man with metastatic melanoma developed colitis secondary to ipilimumab, a known immune-related adverse event (irAE). The patient then received pembrolizumab immunotherapy, an anti-programmed-death-receptor-1 (PD-1) antibody. Restaging FDG PET/CT study following 3 cycles of therapy demonstrated diffuse increased FDG uptake throughout the body of the pancreas associated with fat stranding in the peripancreatic region, suggestive of pembrolizumab-induced pancreatitis. Although the patient was clinically asymptomatic, diagnosis was biochemically confirmed with elevated amylase and lipase levels. In the era of immunotherapy, it will be critical to recognize irAEs early to allow prompt initiation of appropriate therapy and reduce the risk of long-term sequelae.

Molecular targets to promote central nervous system regeneration.

Trauma in the adult mammalian central nervous system (CNS) results in devastating clinical consequences due to the failure of injured axons to spontaneously regenerate. This regenerative failure can be attributed to both a lack of positive cues and to the presence of inhibitory cues that actively prevent regeneration. Substantial progress has been made in elucidating the molecular identity of negative cues present at the CNS injury site following injury. In the past several years, multiple myelin-associated inhibitors including Nogo, Myelin-associated glycoprotein and Oligodendrocyte-myelin glycoprotein have been characterized. Furthermore a neuronal receptor complex and several intracellular substrates leading to outgrowth inhibition have been identified. Rapid progress has also been made in identifying the role of neurotrophins and other positive cues in promoting axonal regrowth. The most recent advances in our understanding of positive stimuli for axon regeneration come from transplantation studies at the CNS lesion site. A number of artificial substrates, tissues, and cells including fetal cells, neural stem cells, Schwann cells and olfactory-ensheathing cells have been tested in animal models of CNS injury. Based on our expanded knowledge of inhibitory influences and on the positive characteristics of various transplants, a number of interventions have been tested to promote recovery in models of CNS trauma. These advances represent the first steps in developing a viable therapy to promote axon regeneration following CNS trauma.

Solitary extramedullary plasmacytoma of the parotid gland imaged with 18F-FDG PET/CT.

A 75-year-old woman presented with a 1-year history of an enlarging mass in the left parotid gland. Biopsy revealed a parotid plasmacytoma, and the patient was referred for a staging F-FDG PET/CT to evaluate the presence of multiple myeloma bone involvement. The PET/CT scan showed intense FDG uptake in the neck mass but no FDG-avid lymphadenopathy or distant metastases. Plasmacytoma involving the parotid gland is extremely rare. We present the F-FDG PET/CT imaging of solitary parotid plasmacytoma.

Recurrent parathyroid carcinoma appearing as FDG negative but MIBI positive.

A 44-year-old woman with recurrent parathyroid carcinoma (PTC) presents with moderately elevated parathyroid hormone and ionized calcium levels. Dual-phase Tc-MIBI SPECT study of the neck and chest demonstrated 2 new foci in keeping with neoplastic seeding. A restaging whole-body F-FDG PET/CT showed no evidence of FDG uptake in the region of the MIBI-positive foci or any evidence of distant metastases. The role of F-FDG PET/CT for imaging PTC is still somewhat limited because of the rarity of this disease. We present a case highlighting a potential pitfall for FDG PET in detecting PTC.

Giant Cell Tumor Pulmonary Metastases Mimic Primary Malignant Pulmonary Nodules on (18)F-FDG PET/CT.

A 59-year-old man with a 30-year history of multiple recurrences of a giant cell tumor (GCT) of the left knee was referred for an (18)F-FDG PET/CT to evaluate a solitary pulmonary nodule. The nodule was mildly FDG-avid, raising suspicion of malignancy. It was excised and histologically proven to be a GCT pulmonary metastasis. A follow-up PET/CT done 2 years later revealed a new, larger lung mass that was more intensely FDG-avid, but of the same histology. This rare report highlights a pitfall in the evaluation of solitary pulmonary lesions by (18)F-FDG PET/CT in patients with GCT of the bone.

The appearance of osseous PEComa on F-18 FDG PET/CT.

A 29-year-old male presented with a 6-month history of left hip pain. Radiography and CT demonstrated a 6-cm lytic lesion of the left acetabulum. F-18 FDG PET for staging of the biopsy-proven malignant PEComa demonstrated intense hypermetabolism corresponding to the lytic left acetabulum. The patient underwent left hemipelvectomy with reconstructive surgery. On a follow-up F-18 FDG PET scan 3 months after initial surgery, a left lung pleural-based 9-mm nodule with hypermetabolism (SUVmax 4.1) was discovered and pathologically proven to be metastases from the primary osseous PEComa.