Imaging of Tumor-Associated Vascular Prostate-Specific Membrane Antigen in Woodchuck Model of Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Radiolabeled short peptide ligands targeting prostate-specific membrane antigen (PSMA) were developed initially for imaging and treatment of prostate cancers. While many nonprostate solid tumors including hepatocellular carcinoma (HCC) express little PSMA, their neovasculature expresses a high level of PSMA, which is avid for Gallium-68-labeled PSMA-targeting radio-ligand (68Ga-PSMA-11) for positron emission tomography (PET). However, the lack of a spontaneous animal model of tumor-associated vascular PSMA overexpression has hindered the development and assessment of PSMA-targeting radioligands for imaging and therapy of the nonprostatic cancers. We identified detectable indigenous PSMA expression on tumor neovascular endothelia in a naturally occurring woodchuck model of HCC. METHODS: Molecular docking was performed with 3 bait PSMA ligands and compared between human and woodchuck PSMA. Initially, PET images were acquired dynamically after intravenously injecting 37 MBq (1.0 mCi) of 68Ga-PSMA-11 into woodchuck models of HCC. Subsequently, 10-minute static PET scans were conducted for other animals 1-hour after injection due to HCC and liver background uptake stabilization at 30-45 minutes after injection. Liver tissue samples were harvested after imaging, fresh-frozen for quantitative reverse transcription polymerase chain reaction and western blot for validation, or fixed for histology for correlation. RESULTS: Our preclinical studies confirmed the initial clinical findings of 68Ga-PSMA-11 uptake in HCC. The agents (ligands and antibodies) developed against human PSMA were found to be reactive against the woodchuck PSMA. CONCLUSION: This animal model offers a unique opportunity for investigating the biogenesis of tumor-associated vascular PSMA, its functional role(s), and potentials for future treatment strategies targeting tumor vascular PSMA using already developed PSMA-targeting agents.

68Ga-Prostate-Specific Membrane Antigen Focal Pulmonary Activity With No Corresponding CT Abnormality.

ABSTRACT: We describe a case of 68Ga-prostate-specific membrane antigen PET/CT scan with focal tracer concentration in the lung without any abnormalities in the CT part. 18F-FDG focal uptake in lungs without corresponding CT lesions is described. Two possible mechanisms proposed to explain this finding in FDG PET/CT scans are iatrogenic pulmonary microembolism and 18F-FDG-avid infection or inflammation that precedes structural findings. Logically, these proposed mechanisms seem to be applicable to 68Ga-prostate-specific membrane antigen as well. In our case, there were no features of any lung infection/inflammation, and the most plausible explanation would be iatrogenic microembolism.

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.

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 in Suspected Renal Cell Carcinoma.

A 60-year-old man with suspected right renal cell carcinoma underwent F-FDG PET/CT and F prostate-specific membrane antigen (PSMA) 1007 PET/CT scan. Compared with the F-FDG PET/CT scan, F-PSMA 1007 PET/CT showed intense tracer concentration in the primary tumor in the right kidney and intense tracer concentration consistently in all lung nodules. Unlike noted in previous pilot studies with Ga-PSMA, we observed that the primary renal tumor also showed intense tracer avidity with F-PSMA 1007. F-PSMA 1007 PET/CT may provide preoperative insight into possible etiology, histopathological probability of tumor type, staging information, and theranostic potentials in evaluation of suspected renal cell carcinoma.

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.

Gallium 68-PSMA PET/CT for lesion characterization in suspected cases of prostate carcinoma.

OBJECTIVE: To assess the feasibility of gallium 68 (Ga)-prostate specific membrane antigen (PSMA) PET/computed tomography (CT) to identify patients who truly harbor clinically significant prostate cancer (PCa) in a cohort of patients with clinical and biochemical/radiological suspicion of PCa. PATIENTS AND METHODS: A total of 118 patients with suspected PCa who underwent Ga-PSMA PET/CT between May 2015 and June 2016 were prospectively included. Final decision on performing biopsy was left to the referring urologist after considering the clinical data, scan findings and discussion with the patient. RESULTS: Overall, 51 patients were scan negative, among whom six underwent biopsy but was negative for malignancy. In 45 patients, an immediate biopsy could be avoided and put on follow-up. None of these patients were documented to have PCa in the short average follow-up of 6 months. Among 67 patients who were scan positive, 56 patients underwent transrectal ultrasonography-guided biopsy, and malignancy could be documented in 46 of them. In addition, comprehensive initial staging information could be obtained in them, with organ-confined disease demonstrated in 33 patients and metastatic disease in 13 patients. CONCLUSION: Ga-PSMA PET/CT can act as a gate keeper in selecting patients with suspected PCa who should undergo an immediate transrectal ultrasonography-guided biopsy and who could be kept on active surveillance.

Utility of 68Ga-PSMA-11 PET/CT in Imaging of Glioma-A Pilot Study.

BACKGROUND: Imaging of gliomas remains challenging. The aim of the study was to assess the feasibility of using Ga-PSMA-11 PET/CT for imaging gliomas. METHODS: Fifteen patients with glioma from 2 centers were included in the study. Ten patients were treated cases of glioblastoma with suspected recurrence. Two patients were sent for assessing the nature (primary lesion/metastasis) of space-occupying lesion in the brain; 3 patients were imaged immediately after surgery and before radiotherapy. Target-to-background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background. RESULTS: Among the 10 cases with suspected recurrence, scan was positive in 9, subsequent surgery was done, and histopathology proved it to be true recurrence. In the scan-negative case on follow-up, no evidence of disease could be made clinically or radiologically. Among the other cases the presence or absence of disease could be unequivocally identified on the Ga-PSMA-11 brain scan and correlated with the histopathology or other imaging. Apart from the visual assessment quantitative assessment of the lesions with TBR also showed a significantly high TBR value for those with true disease compared with those with no disease. CONCLUSIONS: In the evaluation of gliomas, Ga-PSMA-11 PET/CT brain imaging is a potentially useful imaging tool. The use of Ga-PSMA-11 brain PET/CT in evaluation of recurrent glioma seems promising. Absence of physiological uptake of Ga-PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of glioma lesions.

Rare Case of Intratracheal Metastasis Detected on 68Ga-Prostate-Specific Membrane Antigen PET/CT Scan in a Case of Thyroglobulin Elevated Negative Iodine Scan Syndrome.

A 64-year-old woman underwent completion thyroidectomy with upper tracheal ring resection and right-sided neck dissection for papillary carcinoma of the thyroid infiltrating the trachea and was given I radioiodine treatment. Three years later, she presented with hemoptysis. On evaluation, she had increased serum thyroglobulin and negative iodine scan (TENIS). F-FDG PET/CT scan did not identify any site of disease. One year later, Ga-PSMA scan done revealed a moderate focal tracer-avid intratracheal soft tissue; biopsy revealed it to be metastatic papillary carcinoma of the thyroid. This case kindles the possibility of using Ga-PSMA PET/CT to reveal occult disease in cases of TENIS.

Case of Carcinoma Breast with Unusually Large Tumor Thrombus in Superior Vena Cava Detected on 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography Scan.

A 60-year-old female with triple negative breast cancer, postsurgery, neoadjuvant chemotherapy and radiotherapy, on follow-up had facial puffiness and giddiness. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) done for suspected recurrence evaluation revealed a large tumor thrombus (TT) in superior vena cava (SVC) with radiological evidence of SVC obstruction. 18F-FDG PET/CT also showed evidence of FDG avid brain metastases, lymph nodal metastases, and metastatic soft tissue deposits. This case of unusually large TT in SVC detected on 18F-FDG PET/CT highlights the ability of 18F-FDG PET/CT to identify TT and clearly demonstrate the pattern of disease in suspected recurrence in triple negative breast cancer patients.

68Ga-PSMA Uptake in an Incidentally Detected Gastrointestinal Stromal Tumor in a Case of Suspected Carcinoma Prostate.

A 74-year-old man with suspected prostate cancer and a previously negative transrectal ultrasound-guided prostate biopsy underwent Ga-PSMA PET/CT. Scan showed no abnormal tracer concentration in enlarged prostate gland to suggest prostate cancer. Note was made of an incidentally detected well defined soft tissue lesion in the greater curvature of the stomach with moderate tracer concentration in its intraluminal portion. Biopsy of the lesion revealed gastrointestinal stromal tumor.

False Positive Uptake in Bilateral Gynecomastia on 68Ga-PSMA PET/CT Scan.

A 66-year-old man on hormonal therapy with prostate cancer was referred for Ga-PSMA PET/CT scan for biochemical recurrence. Ga-PSMA PET/CT scan detected moderate heterogeneous tracer concentration in bilateral breast parenchyma, in addition to the abnormal tracer concentration in enlarged prostate gland, right external iliac lymph node, and sclerotic lesion in L4 vertebra. On clinical examination, he was found to have bilateral gynecomastia. Abnormal concentration of Ga-PSMA in breast cancer is now well known, and in this context, it is important to know that tracer localization can occur in gynecomastia as well, as evidenced in this case.

Specificity of 68Ga-PSMA PET/CT for Prostate Cancer - Myths and Reality.

68Ga-PSMA ligand PET/CT for imaging prostate cancer is a novel imaging technique, which is rapidly gaining popularity. Sufficient evidence has been accumulated in literature regarding the usefulness of 68Ga-PSMA PET/CT in prostate cancer. Recently literature regarding the localization of 68Ga-PSMA PET/CT imaging in non-prostatic malignancies is also published, thus questioning the specificity of the tracer with regards to prostate cancer. This commentary tries to address the issue of specificity of 68Ga-PSMA PET/CT and its relevance in imaging prostate cancer.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scan in an Unusual Case of Lymphoma with Secondary Involvement of Uterine Cervix Presenting as a Pathological Fracture.

A 48-year-old female presented with a pathological fracture of the right femur. 99mTc methylene diphosphonate bone scan revealed multiple areas of increased osteoblastic activity consistent with metastatic disease. Serum electrophoresis revealed monoclonal gammopathy. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan revealed metabolically active lesions in bulky uterine cervix and osteolytic skeletal lesions. Unusual pattern of FDG uptake in uterine cervix and osteolytic skeletal lesions warranted a biopsy of the uterine cervix which revealed diffuse large B-cell lymphoma. 18F-FDG PET/CT scan helped in guiding the site of biopsy to reach a final diagnosis in this unusual case of lymphoma with a secondary involvement of uterine cervix presenting as a pathological fracture.

68Ga-PSMA PET/CT in Osteosarcoma in Fibrous Dysplasia.

Fibrous dysplasia (FD) is a benign bone lesion with a rare but potential for malignant transformation. Neither Tc-MDP nor F-FDG PET/CT can differentiate between FD and areas of malignant transformation in FD. We described a case of osteosarcoma developing in FD with selective uptake of tracer in malignant transformation areas demonstrated on a Ga-PSMA PET/CT scan. Our case highlights the ability of Ga-PSMA PET/CT to map tumor neoangiogenesis in osteosarcoma arising in FD, which can have potential implications in prognostication, possibility of antiangiogenesis-based therapeutic options, and in response assessment following chemotherapy.

Adenosine Stress Induced Left Bundle Branch Block During Technetium-99m Tetrofosmin Myocardial Perfusion Imaging.

The occurrence of left bundle branch block (LBBB) in electrocardiogram during exercise testing is a relatively rare finding. The incidence of LBBB during exercise testing ranges from 0.5% to 1.1%. The mechanism of exercise-induced LBBB (EI-LBBB) is poorly understood, but ischemia is a proposed etiology. Stress myocardial perfusion imaging (MPI) can be useful in patients with EI-LBBB to rule out coronary artery disease. Adenosine vasodilator stress is the preferred mode of stress in patients with LBBB for performing stress-MPI. Here we present an interesting case of adenosine-induced LBBB during stress-MPI in a 67-year-old female patient with normal coronary angiography.

68Ga PSMA PET/CT in a Rare Case of Metastatic Adenocarcinoma Prostate Presenting as Numb Chin Syndrome.

A 68-year-old man presented with right-side facial numbness. MRI showed an extra-axial mass infiltrating the right temporal bone. It was debulked surgically, and histopathology revealed metastatic adenocarcinoma. Ga PSMA PET/CT done in view of increased PSA levels and clinically suspicious hard lesion in prostate showed primary lesion in left side of prostate with metastases to the right temporal bone. Primary carcinoma of the prostate and metastases to the right temporal bone were proven histopathologically. Our case highlights the usefulness of Ga PSMA PET/CT in identifying the primary site in suspected prostate cancer and mapping the metastatic sites.

68Ga-PSMA PET/CT Imaging in Multiple Myeloma.

The potential applications of Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in the imaging of prostate cancer are now well established. A few case reports regarding the potential use of Ga-PSMA PET/CT in nonprostate cancer malignancies are also published. Apparently, the tumor neoangiogenesis is the mechanism attributed to increased Ga-PSMA uptake in the tumor sites in nonprostatic malignancies. We describe the use of Ga-PSMA PET/CT in imaging multiple myeloma. The intense Ga-PSMA avidity of the lesions also opens up the possibility of theranostics with Lu-PSMA.