Imaging Fibrosis.

Tissue injury in nonmalignant human disease can develop from either disproportionate inflammation or exaggerated fibrotic responses. The molecular and cellular fundamental of these 2 processes, their impact on disease prognosis and the treatment concept deviates fundamentally. Consequently, the synchronous assessment and quantification of these 2 processes in vivo is extremely desirable. Although noninvasive molecular techniques such as 18F-fluorodeoxyglucose PET offer insights into the degree of inflammatory activity, the assessment of the molecular dynamics of fibrosis remains challenging. The 68Ga-fibroblast activation protein inhibitor-46 may improve noninvasive clinical diagnostic performance in patients with both fibroinflammatory pathology and long-term CT-abnormalities after severe COVID-19.

Enhancing Clinical Diagnosis for Patients With Persistent Pulmonary Abnormalities After COVID-19 Infection: The Potential Benefit of 68 Ga-FAPI PET/CT.

PATIENTS AND METHODS: Six post COVID-19 patients suspected for pulmonary fibrosis were scheduled for dual-tracer PET/CT with 18 F-FDG and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46. The uptake of 68 Ga-FAPI-46 in the involved lung was compared with a control group of 9 non-COVID-19 patients. Clinical data and PET/CT imaging were collected and analyzed. RESULTS: PET/CT revealed in all 6 pulmonary impaired patients the reduced glucose avidity on 18 F-FDG and clear positivity on 68 Ga-FAPI-46 PET/CT in comparison to the control group. CONCLUSIONS: Enhancing fibrotic repair mechanisms, 68 Ga-FAPI PET/CT may improve noninvasive clinical diagnostic performance in patients with long-term CT abnormalities after severe COVID-19. Although this study shows promising results, additional studies in larger populations are required to establish a general diagnostic guideline.

Tracheitis Diagnosed With 68 Ga-PSMA PET/CT in a Patient With COVID-19.

ABSTRACT: A 57-year-old man with newly diagnosed with prostate cancer was admitted to our department for 68 Ga-prostate-specific membrane antigen PET/CT imaging. The patient, who was asymptomatic at the time of imaging, had increased diffuse 68 Ga-prostate-specific membrane antigen uptake in the trachea on PET/CT. No ground-glass density suggestive of pneumonia in both lungs was observed. The patient, whose symptoms developed 2 days after PET/CT imaging, was diagnosed with coronavirus disease 2019 by real-time polymerase chain reaction.

Application of 68Ga-PSMA-11 PET/CT in the Diagnosis of Prostate Cancer Clinical Relapse.

BACKGROUND: This work aims to present a nuclear medicine imaging service's data regarding applying positron emission-computing tomography (PET/CT) scans with the radiopharmaceutical 68Ga-PSMA-HBED-CC (68Ga-PSMA-11) to diagnose prostate cancer clinical relapse. METHODS: Eighty patients with a mean age of 68.26 years and an average prostatic-specific antigen blood level of 7.49 ng/ml (lower concentration = 0.17 ng/ml) received 68Ga-PSMA-11 intravenously, and full-body images of PET-CT scan were obtained. Of the total of patients admitted to the imaging service, 87.5% were examined for disease's biochemical recurrence and clinical relapse, and 70.0% had a previous radical prostatectomy (RP). RESULTS: Of the patients without RP, 95.8% were detected with intra-glandular disease. The 68Ga- PSMA-11 PET/CT imaging results revealed small lesions, even in patients with low blood levels of prostatic-specific antigen, mainly in metastatic cancer cases in lymph nodes and bones. CONCLUSION: The 68Ga-PSMA-11 PET/CT imaging was essential in detecting prostate cancer, with significantly high sensitivity in detecting recurrent cases. Due to its inherent reliability and sensitivity, PET/CT scanning with 68Ga-PSMA-11 received an increasing number of medical requests throughout the present follow-up study, confirming the augmented demand for this clinical imaging procedure in the regional medical community.

New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer's Disease Research.

Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer's disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are crucial for the potential application as diagnostic radiopharmaceuticals. A set of ten tacrine derivatives was synthesized, labelled with gallium-68 and fully characterized in the context of their physicochemical properties. Based on these results, the final two most promising radioconjugates, [68Ga]Ga-NODAGA-Bn-NH(CH2)9Tac and [68Ga]Ga-THP-NH(CH2)9Tac, were selected for biodistribution studies. The latter compound was proven to be a good inhibitor of cholinesterases with significant affinity toward the lungs, according to the biodistribution studies. On the basis of molecular modelling combined with in vitro studies, we unraveled which structural properties of the developed tacrine derivatives are crucial for high affinity toward acetylcholinesterase, whose increased levels in lung tissues in the course of coronavirus disease indicate the onset of pneumonia. The radiopharmaceutical [68Ga]Ga-THP-NH(CH2)9Tac was ultimately selected due to its increased accuracy and improved sensitivity in PET imaging of lung tissue with high levels of acetylcholinesterase, and it may become a novel potential diagnostic modality for the determination of lung perfusion, including in inflammation after COVID-19.

Vaccine-Related Lymph Nodes: The Emerging Pitfalls of 18F-Fluorocholine and 68Ga-PSMA-11 PET/CT in the Era of COVID-19 Vaccination.

PURPOSE: Vaccination against coronavirus disease 2019 (COVID-19) is currently under worldwide deployment. The consequences of this vaccination can be seen in radiology and nuclear medicine explorations with visualization of axillary lymph nodes (LNs), as observed on ultrasonography, MRI, or 18F-FDG PET/CT.We aimed to evaluate on PET/CT the incidence of vaccine-related LNs and their characteristics after COVID-19 vaccination, using several radiopharmaceuticals different from 18F-FDG. PATIENTS AND METHODS: Between February and July 2021, all consecutive patients undergoing a whole-body PET/CT for any indication using a different radiopharmaceutical from 18F-FDG were eligible for inclusion if they had received at least 1 dose of the COVID-19 vaccine. The radiopharmaceutical administered and vaccine type were recorded for each patient. The incidence of positive vaccine-related axillary and supraclavicular LNs on PET/CT was our primary finding, along with the nodes characteristics. Statistical analyses were performed for patients with prostate cancer (PCa) to determine certain interaction factors that were associated with the detection of vaccine-related LNs. RESULTS: Of the 226 patients in our cohort study, 120 patients underwent an 18F-fluorocholine PET/CT, 79 a 68Ga-PSMA-11 PET/CT, 6 an 18F-FDOPA PET/CT, and 21 a 68Ga-DOTATOC PET/CT. A total of 67.3% of patients (152/226) received BNT162b2mRNA (Pfizer-BioNTech), 26.5% (60/226) ChAdOx1-S (AstraZeneca), 4.9% (11/226) mRNA-1273 (Moderna), and 1.3% (3/226) Ad26.COV2.S (Janssen). The incidence of positive vaccine-related axillary and supraclavicular LNs was 42.5% (51/120 patients) on PET/CT using 18F-fluorocholine and 12.7% (10/79 patients) with 68Ga-PSMA-11. None of our patients undergoing 18F-FDOPA or 68Ga-DOTATOC PET/CT presented any vaccine-related lymphadenopathy. Vaccine-related LNs were statistically associated with the nature of the radiopharmaceutical (P < 10-4), with the number of vaccine doses received (P = 0.041), with a short delay between vaccination and PET/CT realization (P < 10-5), and with a higher prostate-specific antigen level for patients with PCa (P = 0.032), but not with age or vaccine type. The vaccine-related nodes appeared in 85% of the cases, in the 30 days after vaccine injection, were limited in size and uptake, and were most often limited to the axilla level 1 area. CONCLUSIONS: Detecting positive LNs after COVID-19 vaccination is not an exclusive 18F-FDG PET/CT pattern but is common on 18F-fluorocholine and possible on 68Ga-PSMA-11 PET/CT. Confronting PET/CT findings with clinical data (such as date and site of injection) seems essential in the current pandemic context, just as it does for the radiopharmaceuticals used in PCa to avoid PET/CT misinterpretation and incorrect patient treatment. For 18F-FDOPA or 68Ga-DOTATOC PET/CT, this seems to have a lesser impact.

Detection of COVID-19 Incidentally in 68Ga-PSMA PET/CT for Restaging of Prostate Cancer.

BACKGROUND: A series of pneumonia cases with clinical presentations of viral pneumonia secondary to new coronavirus and subsequent global transmission arose in Wuhan, Hubei, China, in December 2019. Several cases of coronavirus disease 2019 (COVID-19) have been described incidentally in positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) as a result of the pandemic. Herein, we describe the findings of a patient with unknown COVID-19 in PET/CT with the other radiopharmaceutical, 68Ga-labeled prostatespecific membrane antigen (68Ga-PSMA). CASE REPORT: A 69-year-old man had previously undergone radical prostatectomy for adenocarcinoma. 68Ga-PSMA PET/CT imaging was performed due to biochemical recurrence. 68Ga-PSMA uptake in the prostate bed suggestive of local recurrence was detected in PET/CT images. Also, bilateral groundglass opacities with slightly increased 68Ga-PSMA uptake were seen in the lungs, suspected of COVID-19. A reverse transcription-polymerase chain reaction test has confirmed the infection. CONCLUSION: Even in asymptomatic patients, nuclear medicine departments must be aware of the possibility of COVID-19, take appropriate post-exposure procedures, and protect employees and other patients.

COVID-19 Lung Findings Detected by 68Ga-PSMA PET/CT for Staging Purposes in Patients With Prostate Cancer.

ABSTRACT: We report 3 patients with COVID-19 findings in 68Ga-PSMA PET/CT taken for staging. The first patient, A 64-year-old man with prostate cancer, who had COVID-19 in November 2020 and whose treatment was completed, was observed to continue with COVID-19 findings in 68Ga-PSMA PET/CT in December 2020 before surgery. Other patients were asymptomatic for the disease. It was determined that a PSMA uptake in the lungs corresponding to the CT findings of COVID-19 had increased in 68Ga-PSMA PET/CT.

Cyclic 68Ga-Labeled Peptides for Specific Detection of Human Angiotensin-Converting Enzyme 2.

In this study, we developed angiotensin-converting enzyme 2 (ACE2)-specific, peptide-derived 68Ga-labeled radiotracers, motivated by the hypotheses that ACE2 is an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and that modulation of ACE2 in coronavirus disease 2019 (COVID-19) drives severe organ injury. Methods: A series of NOTA-conjugated peptides derived from the known ACE2 inhibitor DX600 were synthesized, with variable linker identity. Since DX600 bears 2 cystine residues, both linear and cyclic peptides were studied. An ACE2 inhibition assay was used to identify lead compounds, which were labeled with 68Ga to generate peptide radiotracers (68Ga-NOTA-PEP). The aminocaproate-derived radiotracer 68Ga-NOTA-PEP4 was subsequently studied in a humanized ACE2 (hACE2) transgenic model. Results: Cyclic DX-600-derived peptides had markedly lower half-maximal inhibitory concentrations than their linear counterparts. The 3 cyclic peptides with triglycine, aminocaproate, and polyethylene glycol linkers had calculated half-maximal inhibitory concentrations similar to or lower than the parent DX600 molecule. Peptides were readily labeled with 68Ga, and the biodistribution of 68Ga-NOTA-PEP4 was determined in an hACE2 transgenic murine cohort. Pharmacologic concentrations of coadministered NOTA-PEP (blocking) showed a significant reduction of 68Ga-NOTA-PEP4 signals in the heart, liver, lungs, and small intestine. Ex vivo hACE2 activity in these organs was confirmed as a correlate to in vivo results. Conclusion: NOTA-conjugated cyclic peptides derived from the known ACE2 inhibitor DX600 retain their activity when N-conjugated for 68Ga chelation. In vivo studies in a transgenic hACE2 murine model using the lead tracer, 68Ga-NOTA-PEP4, showed specific binding in the heart, liver, lungs and intestine-organs known to be affected in SARS-CoV-2 infection. These results suggest that 68Ga-NOTA-PEP4 could be used to detect organ-specific suppression of ACE2 in SARS-CoV-2-infected murine models and COVID-19 patients.

68Ga-DOTATATE PET/CT for Neuroblastoma Staging: Utility for Clinical Use.

Metaiodobenzylguanidine (MIBG) imaging has been the standard for neuroblastoma staging for many decades. Novel agents such as 18F-DOPA and 68Ga-DOTATATE are being used nowadays in academic centers. During the coronavirus disease 2019 (COVID-19) pandemic, procurement of 123I-MIBG has proved particularly challenging, necessitating the use of 68Ga-DOTATATE PET. 68Ga-DOTATATE is Food and Drug Administration-approved for imaging of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Methods: 68Ga-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: 68Ga-DOTATATE PET/CT scans were successfully performed on all patients. All patients showed 68Ga-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 68Ga-DOTATATE PET/CT imaging for staging of neuroblastoma and believe it can reliably be used as an alternative to 123I-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.

Molecular PET/CT Profiling of ACE2 Expression In Vivo: Implications for Infection and Outcome from SARS-CoV-2.

Rapid progress has been made to identify and study the causative agent leading to coronavirus disease 2019 (COVID-19) but many questions including who is most susceptible and what determines severity remain unanswered. Angiotensin-converting enzyme 2 (ACE2) is a key factor in the infection process of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this study, molecularly specific positron emission tomography imaging agents for targeting ACE2 are first developed, and these novel agents are evaluated in vitro, in preclinical model systems, and in a first-in-human translational ACE2 imaging of healthy volunteers and a SARS-CoV-2 recovered patient (NCT04422457). ACE2 expression levels in different organs in live subjects are quantitatively delineated and observable differences are measured in the patient recovered from COVID-19. Surprising sites of uptake in the breast, reproductive system and very low uptake in pulmonary tissues are reported. This novel method can add a unique tool to facilitate SARS-CoV-2 related research and improve understanding of this enigmatic disease. Molecular imaging provides quantitative annotation of ACE2, the SARS-CoV-2 entry receptor, to noninvasively monitor organs impacted by the COVID-19.

68Ga-PSMA PET/CT With Incidental Finding of COVID-19 in an Asymptomatic Patient.

A 70-year-old man with prostate adenocarcinoma was diagnosed by transrectal biopsy, with Gleason of 4 + 5 and initial PSA of 225 ng/mL since March 2020. Ga-PSMA PET/CT was performed as part of initial staging. The images showed an enlarged prostate with focal PSMA uptake in both lobes. Retroperitoneal and pelvic lymph nodes with moderate uptake of PSMA were shown. Another finding was a moderate PSMA uptake in the both lung parenchymas associated with opacities in CT. The patient denied any symptoms of coronavirus disease and was referred to the emergency department for RT-PCR COVID-19, and the result was positive.

Unknown SARS-CoV-2 pneumonia detected by PET/CT in patients with cancer.

INTRODUCTION: In January 2020, the coronavirus disease 2019 (COVID-19) outbreak in Italy necessitated rigorous application of more restrictive safety procedures in the management and treatment of patients with cancer to ensure patient and staff protection. Identification of respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was a challenge during the pandemic owing to a large number of asymptomatic or mildly symptomatic patients. METHODS: We report 5 patients with unknown SARS-CoV-2 infection undergoing positron emission tomography (PET)/computed tomography (CT) with radiopharmaceuticals targeting different tumor processes: 18F-FDG, 18F-choline (FCH), and 68Ga-PSMA. RESULTS: In all patients, PET/CT showed increased tracer uptake in the lungs corresponding to CT findings of SARS-CoV-2 pneumonia. Quantitative assessment of tracer uptake showed more elevated values for the glucose analogue 18F-FDG (mean SUVmax 5.4) than for the other tracers (mean SUVmax 3.5). CONCLUSIONS: Our findings suggest that PET/CT is a sensitive modality to hypothesize SARS-CoV-2 pneumonia in patients with cancer, even when asymptomatic. More data are needed to verify the correlation among immune response to SARS-CoV-2 infection, clinical evolution, and PET results. Under the strict safety measures implemented at the PET center, the number of potentially SARS-CoV-2-positive patients undergoing PET/CT was very low (1.6%), and no staff member has been diagnosed with infection as of April 30, 2020.