The role of prostate-specific membrane antigen PET/computed tomography in the management of prostate cancer patients: could we ask for more?

PURPOSE OF REVIEW: Thanks to the development of novel PSMA-based peptides, molecular imaging, such as PET/CT paired with theranostic-based approaches have recently been proposed for treatment of prostate cancer. Patient selection, however, remains challenging because of the absence of strong prospective data to interpret and translate imaging scans into effective and well tolerated treatment regimens. RECENT FINDINGS: In this review, we discuss the latest findings in PSMA imaging in prostate cancer patients. Particularly, we go into detail into the impact of PSMA imaging on the treatment management in primary staging, biochemical recurrence and in advanced prostate cancer. SUMMARY: For primary prostate cancer staging, PSMA PET/CT seems crucial for primary therapy assessment, being able in some cases to detect lesions outside the surgical template, thus permitting a change in management. Moreover, N+ condition at PSMA has been correlated with a worse biochemical recurrence-free and therapy-free survival. The early detection of PSMA-positive findings in recurrent prostate cancer is associated with a better time to relapse survival. Similarly, for advanced prostate cancer patients, accurate restaging with PSMA imaging is gaining importance for early prediction of response to systemic therapies and to assure the best outcome possible. With regards to theranostics, appropriate selection of patients eligible for 177Lu-PSMA requires PSMA imaging, whereas the role of added FDG-PET for discriminating those with PSMA/FDG discordance needs to be further evaluated.

Promise of PET imaging in prostate cancer: improvement or waste of money?

PURPOSE OF REVIEW: Prostate cancer is a high prevalence malignancy whose management is a major challenge for clinicians worldwide. Molecular imaging, and in particular PET with computed tomography (PET/CT), is increasingly gaining importance in the work up and management of all prostate cancer patients. PET/CT remains, however, an expensive imaging modality and currently not reimbursed. RECENT FINDINGS: Although other PET tracers are available and have gained institutional recognition from regulatory agencies, prostate-specific membrane agents (PSMA)-based PET/CT tracers have demonstrated the highest sensitivity and specificity for prostate cancer, outperforming any other PET radioligand to date. Regardless of the clinical scenario (staging, biochemical recurrence, therapy response assessment in advanced prostate cancer) PSMA PET/CT scans have become common practice in countries allowing for use outside of controlled clinical trials because of the overwhelming evidence demonstrating the extremely high sensitivity of this imaging modality in identifying prostate cancer lesions. This evidence can make PSMA PET/CT appealing for clinicians and lead to unnecessary scanning with limited supporting evidence. SUMMARY: Our aim is to provide an update on the most recent literature available on PET-based imaging for prostate cancer and particularly PSMA PET/CT, offering an expert opinion on the data collected to provide clinicians with guidance on appropriateness and efficacy of PET-based imaging, in order to maximize clinical benefits and avoid waste of resources.

Development of standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent lesions.

METHODS: After primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff's (K) alpha<0.61]. Finally, on the basis of the consensus readings, we sought to define a list of revised consensus criteria for 68Ga-PSMA PET/CT interpretation. RESULTS: Between-reader agreement for the presence of anomalous findings in any of the five sites was only moderate (K's alpha: 0.47). The agreement improved and became substantial when readers had to judge whether the anomalous findings were suggestive for a pathologic, uncertain, or non-pathologic image (K's alpha: 0.64). K's alpha calculations for each of the five sites of recurrence were also performed and evaluated. First Delphi round was thus conducted. A more detailed definition of the criteria was proposed by the project coordinator, which was then discussed and finally agreed by the seven readers. After the second Delphi round only four cases of disagreement still remained. These were evaluated for a final round, allowing a final agreement table to be written. CONCLUSION: We hope that by developing these consensus guidelines on the interpretation of 68Ga-PSMA PET/CT, clinicians reporting these studies will be able to provide more consistent clinical reports and that within clinical trials, abnormality classifications will be harmonized, allowing more robust assessment of its diagnostic performance.

¹8F-FDG PET/CT diagnosis of unexpected extracardiac septic embolisms in patients with suspected cardiac endocarditis.

PURPOSE: Acute infective endocarditis is a potentially life-threatening disease. Its outcome strongly depends on systemic embolization and extracardiac infections. When present, these conditions usually lead to a more aggressive therapeutic approach. However, the diagnosis of peripheral septic embolism is very challenging. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has proven to be accurate for the detection of inflammatory diseases and occult infections. The aim of this study was to assess the added value of (18)F-FDG PET/CT in the detection of extracardiac embolisms in the evaluation of patients with suspected valvular endocarditis (VE). METHODS: Seventy-one patients with suspected infective endocarditis, enrolled between June 2010 and December 2012, underwent (18)F-FDG PET/CT with the standard procedure on a dedicated PET/CT scanner. Extracardiac findings were subsequently evaluated with other imaging procedures. RESULTS: Of the 71 patients with suspicion of infective endocarditis, we found unexpected extracardiac findings in 17 patients (24%) without any clinical suspicion. Extracardiac findings were subsequently evaluated with other imaging procedures. CONCLUSION: PET/CT detected unexpected extra sites of infection in 24% of cases, leading to changes in therapeutic management in a very relevant percentage of patients. These findings may have important therapeutic implications.

Theranostics in oncology: What radiologists want to know.

Combination of radioligand imaging and therapy, so called radiotheranostics, is a novel tool of precision oncology with proven clinical value. In-depth knowledge of functional imaging nuances is critically needed for precise prognostication and guidance of management. Here, we review theranostic applications with up to Phase III type evidence for outcome improvement: Imaging and therapy of neuroendocrine neoplasms (NEN) exploiting high levels of somatostatin receptor (SSTR) expression and radiotheranostics of prostate cancer targeting the prostate specific membrane antigen (PSMA). This narrative review focusses on these two applications and elucidates patient selection and response assessment by radioligand scintigraphy and/or positron emission tomography. Furthermore, we provide a brief outlook on future applications for novel targets outside of NEN and prostate cancer.

18F-FDG PET/CT in visceral leishmaniasis: uptake patterns in the context of a multiannual outbreak in Northern Italy.

OBJECTIVES: Visceral leishmaniasis (VL) is the most severe manifestation of the infection caused by the protozoan Leishmania, recently on increase in Italy and Spain. The aim of the study was to describe FDG uptake patterns in VL patients (pts) who underwent 18F-FDG PET/CT. METHODS: A retrospective monocentric study of pts who underwent FDG PET/CT between 2008 and 2017 and later diagnosed with VL was performed. Semi-quantitative parameters were calculated in FDG-positive lesions: SUVmax, SUVmax spleen/SUVmax liver ratio (SLR), SUVmax focal/diffuse spleen ratio (FDR). RESULTS: Overall, 23 pts were included. PET/CT was negative in 2 immunocompromised pts, positive in 21/23 (91%) [6 spleen only, 2 spleen + nodes, 7 spleen + bone marrow (BM), 4 spleen + BM + nodes, 1 spleen + BM + lung, 1 BM only + nodes, 2 nodes only]. Splenic involvement was demonstrated in 20/23 (87%) pts. Two different splenic patterns were observed: diffuse (13/20 pts, mean spleen SUVmax = 7.3 ± 4.2 [4.0-14.1], mean SLR = 2.2 ± 1.6 [1.3-6.7]) and focal over diffuse (7/20 pts, mean SUVmax = 12.6 ± 4.5 [9.5-20.5], mean SLR = 2.8 ± 0.8 [2.1-4.4], mean FDR = 2.1 ± 0.8 [1.2-3.6]). Extra-splenic FDG-avid findings were detected in 15/21 pts (65%): bone marrow in 13/15 (mean SUVmax = 4.0 ± 1.3 [2.8-6.0]), nodes in 67/15 and lung in 1/15. CONCLUSIONS: PET/CT demonstrated splenic FDG uptake in all immunocompetent VL pts; two splenic patterns (diffuse/focal over diffuse) were observed and indistinguishable from splenic involvement by other disorders. The most frequent extra-splenic FDG-positive sites were BM and lymph nodes. Considering the potential disease aggressiveness and recent outbreaks in north-eastern Italy, VL should be considered in the differential diagnosis of FDG-positive splenic findings in pts from endemic areas or reporting travels to endemic countries.

The clinical use of PET with (11)C-acetate.

The aim of this review is to evaluate clinical applications of (11)C-acetate positron emission tomography (PET). Acetate is quickly metabolized into acetyl-CoA in human cells. In this form it can either enter into the tricarboxylic acid cycle, thus producing energy, as happens in the myocardium, or participate in cell membrane lipid synthesis, as happens in tumor cells. (11)C-acetate PET was originally employed in cardiology, to study myocardial oxygen metabolism. More recently it has also been used to evaluate myocardial perfusion, as well as in oncology. The first studies of (11)C-acetate focused on its use in prostate cancer. Subsequently, (11)C-acetate was studied in other urological malignancies, as well as renal cell carcinoma and bladder cancer. Well differentiated hepatocellular carcinoma represents an (18)F-fluoro-deoxyglucose ((18)F-FDG) PET pitfall, so many authors have proposed to use (11)C-acetate in addition to (18)F-FDG in studying this tumor. (11)C-acetate PET has also been used in other malignancies, such as brain tumors and lung carcinoma. Some authors reported a few cases in which (11)C-acetate PET incidentally found multiple myeloma or rare tumors, such as thymoma, multicentric angiomyolipoma of the kidney and cerebellopontine angle schwannoma. Lastly, (11)C-acetate PET was also employed in a differential diagnosis case between glioma and encephalitis. The numerous studies on (11)C-acetate have demonstrated that it can be used in cardiology and oncology with no contraindications apart from pregnancy and the necessity of a rapid scan. Despite its limited availability, this tracer can surely be considered to be a promising one, because of its versatility and capacity to even detect non (18)F-FDG-avid neoplasm, such as differentiated lung cancer or hepatocellular carcinoma.