Prostate cancer: nuclear medicine imaging in the biochemical recurrence and in oligometastatic disease.

INTRODUCTION: The aim of this article was to offer a comprehensive non-systematic review of the literature about the use of Nuclear Medicine imaging exams for the evaluation of prostate cancer (PCa) in the recurrent setting, with a particular regard to positron emission tomography/computed tomography (PET/CT) imaging. EVIDENCE ACQUISITION: A comprehensive nonsystematic literature review was performed in March 2024. Literature search was updated until March 2024. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations. EVIDENCE SYNTHESIS: Restaging BCR with advanced Nuclear Medicine Imaging, such as prostate-specific membrane antigen-PET/CT could lead to stage migration and pave the way for additional management strategies, such as stereotactic ablative radiotherapy in patients with low-burden or oligometastatic disease, potentially delaying the need of systemic therapies. While OS benefits of targeting PET/CT positive disease are still lacking, data on progression- and metastasis-free-survival are emerging. Improvements in quality-of-life assessments are already evident. CONCLUSIONS: PCa is one of the most common malignancy in men. In the last 10 years PCa imaging has become significantly more accurate and is now essential for the definition of the extent of the disease in different phases of its natural history. This opened the road to novel management strategies, especially in the recurrent setting, in which the oligometastatic state is now being explored in several trials regarding the prognostic significance of metastasis directed therapies aimed at personalizing the treatment for every single patient.

Alternative Nuclear Imaging Tools for Infection Imaging.

PURPOSE OF REVIEW: Cardiovascular infections are serious disease associated with high morbidity and mortality. Their diagnosis is challenging, requiring a proper management for a prompt recognition of the clinical manifestations, and a multidisciplinary approach involving cardiologists, cardiothoracic surgeons, infectious diseases specialist, imagers, and microbiologists. Imaging plays a central role in the diagnostic workout, including molecular imaging techniques. In this setting, two different strategies might be used to image infections: the first is based on the use of agents targeting the microorganism responsible for the infection. Alternatively, we can target the components of the pathophysiological changes of the inflammatory process and/or the host response to the infectious pathogen can be considered. Understanding the strength and limitations of each strategy is crucial to select the most appropriate imaging tool. RECENT FINDINGS: Currently, multislice computed tomography (MSCT) and nuclear imaging (18F-fluorodeoxyglucose positron emission tomography/computed tomography, and leucocyte scintigraphy) are part of the diagnostic strategies. The main role of nuclear medicine imaging (PET/CT and SPECT/CT) is the confirmation of valve/CIED involvement and/or associated perivalvular infection and the detection of distant septic embolism. Proper patients' preparation, imaging acquisition, and reconstruction as well as imaging reading are crucial to maximize the diagnostic information. In this manuscript, we described the use of molecular imaging techniques, in particular WBC imaging, in patients with infective endocarditis, cardiovascular implantable electronic device infections, and infections of composite aortic graft, underlying the strength and limitations of such approached as compared to the other imaging modalities.

[18F]Fluorocholine PET/CT-guided stereotactic body radiotherapy in patients with recurrent oligometastatic prostate cancer.

BACKGROUND: In the last years, functional imaging has given a significant contribution to the clinical decision-making of biochemically relapsed prostate cancer (PCa). Hereby, we present a prospective study aiming to validate the role of [18F]Fluoro-Methyl Choline ([18F]FMCH) PET/CT in the selection of PCa patients suitable for stereotactic body radiotherapy (SBRT). METHODS: Patients with biochemical recurrence limited up to three lesions revealed by [18F]FMCH PET/CT were enrolled in the present study and treated with SBRT on all active lesions. Systemic therapy-free survival since the [18F]FMCH PET/CT was considered as the primary endpoint. RESULTS: Forty-six patients were evaluated, and a total of 67 lesions were treated. After a median follow-up of 28.9 months, systemic therapy was started in 30 patients (65.2%) and median systemic therapy-free survival was 39.1 months (95% CI 6.5-68.6); 6, 12, and 24-month ratios were 93.5%, 73.9%, and 63.1%, respectively. At univariate Cox regression analysis, Delta PSA demonstrated an impact on systemic therapy-free survival (p < 0.001). CONCLUSIONS: Based on our findings, [18F]FMCH PET/CT can identify oligometastatic prostate cancer patients suitable for SBRT, resulting in a systemic therapy-free survival of 39.1 months.

Ruptured Mycotic Aneurysm After Intravesical Instillation for Bladder Tumor.

BACKGROUND: Intravesical instillation of Bacillus Calmette-Guérin (BCG) is an effective and widely used treatment for patients with in situ bladder cancer. Major complications are quite uncommon, but a systemic dissemination of the attenuated strain of Mycobacterium bovis is possible. Few cases of aortic rupture caused by M bovis infection are described in literature. METHODS: A 70-year-old male, treated 3 months before with BCG instillation, presented to the emergency department because of a ruptured abdominal aortic aneurysm. The patient was hemodynamically stable, with a "hostile" abdomen. Therefore, an Endologix AFX endograft was deployed. During the postoperative period, his blood inflammatory markers increased, suspicious of a graft infection. Single-photon emission computed tomography (CT)/CT scan showed aortic increased uptake. Antibiotic therapy was continued, but after some days, the patient presented with hematemesis, and the CT scan showed an aortoenteric fistula. In emergency, the infected graft and aneurysm were removed, enteric fistula was closed, and an axillobifemoral bypass was performed. The patient died 25 days after endovascular aneurysm repair explantation. RESULTS: Despite the high suspicion of mycotic aortic aneurysm and graft infection by M bovis, there is no proof of this theory because of the absence of any positive culture test. M bovis is a slow-growing bacteria, and specific culture tests are required to identify it; indeed, all our blood and intraoperative samples were positive to other bacteria, probably the contaminant ones. CONCLUSIONS: Mycotic aneurysm is an extremely rare complication of intravesical BCG therapy, but it must be taken into consideration in patients with rapidly growing aortic aneurysms or rupture of a normal aorta, who have been previously submitted to this kind of instillation.

Radiomics-Based Inter-Lesion Relation Network to Describe [18F]FMCH PET/CT Imaging Phenotypes in Prostate Cancer.

Advanced image analysis, including radiomics, has recently acquired recognition as a source of biomarkers, although there are some technical and methodological challenges to face for its application in the clinic. Among others, proper phenotyping of metastatic or systemic disease where multiple lesions coexist is an issue, since each lesion contributes to characterization of the disease. Therefore, the radiomic profile of each lesion should be modeled into a more complex architecture able to reproduce each "unit" (lesion) as a part of the "entire" (patient). This work aimed to characterize intra-tumor heterogeneity underpinning metastatic prostate cancer using an exhaustive innovative approach which consist of a i) feature transformation method to build an agnostic (i.e., irrespective of pre-existence knowledge, experience, and expertise) radiomic profile of lesions extracted from [18F]FMCH PET/CT, ii) qualitative assessment of intra-tumor heterogeneity of patients, iii) quantitative representation of the intra-tumor heterogeneity of patients in terms of the relationship between their lesions' profiles, to be associated with prognostic factors. We confirmed that metastatic prostate cancer patients encompassed lesions with different radiomic profiles that exhibited intra-tumor radiomic heterogeneity and that the presence of many radiomic profiles within the same patient impacted the outcome.

[18F]-Fludeoxyglucose Positron Emission Tomography/Computed Tomography with Radiomics Analysis in Patients Undergoing Aortic In-Situ Reconstruction with Cryopreserved Allografts.

BACKGROUND: The aim of this study was to evaluate the effectiveness of positron emission tomography/computed tomography with [18F]-fludeoxyglucose (FDG-PET/CT) and radiomics analysis in detecting differences between the native aorta and the abdominal aortic allograft after the total eradication of infection in patients undergoing infected graft removal and in situ reconstruction with cryopreserved allografts. METHODS: Between January 2008 and December 2018, 56 vascular reconstructions with allografts have been performed at our department. The present series included 12 patients undergoing abdominal aortic in situ reconstruction with cryopreserved allografts. During the follow-up, all patients underwent a total-body [18F]FDG PET/CT with subsequent radiomics analysis. In all patients, a comparative analysis between the data extracted from native aorta and cryopreserved graft for each patient was performed. RESULTS: All patients were male with a mean age of 72.8 years (range 63-84). Mean duration of follow-up was 51.3 months (range 3-120). During the follow-up, 2 patients (16.7%) needed a redo allograft-related surgical intervention. Overall, the rate of allograft dilatation was 33.3%. No patient had a redo infection during the follow-up. Radiomics analysis showed a different signature of implanted allograft and native aorta. Comparative analysis between the native aortas and cryopreserved allografts (dilated or not) showed several statistical differences for many texture features. CONCLUSIONS: The higher metabolic activity of allografts could indicate a state of immune-mediated degeneration. This theory should be proven with prospective, multicentric studies with larger sample sizes.

What to Trust, PSA or [68Ga]Ga-PSMA-11: Learn from Experience.

Brain metastases from prostate cancer typically occur in the more advanced stages of the disease. Clinically, the early diagnosis of visceral disease is crucial, impacting on patient's management and prognosis. Although magnetic resonance imaging (MRI) is the modality of choice for the detection of brain metastases, it is not routinely performed in the surveillance of prostate cancer patients unless neurological manifestations appear. Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, overexpressed in more than 90% of prostate cancer cells. This molecular target is a suitable tissue biomarker for prostate cancer functional imaging. We present a case of a 73-year gentleman diagnosed with prostate adenocarcinoma and surgically treated (pT3bN1Mx, Gleason Score of 9) in February 2016. Subsequently, he underwent androgen deprivation therapy because of the occurrence of a bone metastasis. Between 2016 and January 2019 PSA levels were maintained under control. Starting from September 2019, it progressively raised up to 0.85 ng/mL with a doubling time of 3.3 months. Therefore, he performed a [68Ga]Ga-PSMA-11 PET/CT which showed a focal radiopharmaceutical uptake in the right temporal lobe corresponding to the presence of a rounded cystic lesion on brain MRI. The subsequent excisional biopsy diagnosed a prostate adenocarcinoma metastasis. PSMA expression has been reported in brain parenchyma after ischemic strokes and in some brain tumors including gliomas, meningiomas, and neurofibromas. In our case, the lack of symptoms and the relatively low PSA level raised questions about the nature of the lesion, posing the differential diagnosis between brain metastases and primary brain tumor. Finally, our case shows the capability of [68Ga]Ga-PSMA-11 PET/CT to detect metachronous distant brain metastases in a low biochemical recurrent asymptomatic prostate cancer patient, indicating that proper acquisition - from the vertex to thigh - should be always considered, regardless of the PSA level.

Role of Multimodal Imaging in Patients With Suspected Infections After the Bentall Procedure.

Purpose: This study aimed to assess the diagnostic performances of multimodal imaging [i.e., white blood cell single-photon emission computed tomography/CT (99mTc-HMPAO-WBC SPECT/CT) and 18-fluoride-fluorodeoxyglucose positron emission tomography/CT ([18F]FDG PET/CT)] in patients with suspected infection after the Bentall procedure, proposing new specific diagnostic criteria for the diagnosis. Methods: Between January 2009 and December 2019, we selected within a cardiovascular infections registry, 76 surgically treated patients (27 women and 49 men, median 66 years, and range 29-83 years). All the patients underwent molecular imaging for a suspected infection after the replacement of the aortic valve and ascending aorta according to the Bentall procedure. We analyzed 98 scans including 49 99mTc-WBC and 49 [18F]FDG PET/CT. A total of 22 patients with very early/early suspected infection (<3 months after surgery) were imaged with both the techniques. Positive imaging was classified according to the anatomical site of increased uptake: to the aortic valve (AV), to both the AV and AV tube graft (AVTG) or to the TG, to surrounding tissue, and/or to extracardiac sites (embolic events or other sites of concomitant infection). Standard clinical workup included in all the patients having echocardiography/CT, blood culture, and the Duke criteria. Pretest probability and positive/negative likelihood ratio were calculated. Sensitivity and specificity of 99mTc labeled hexamethylpropylene amine oxime-WBC SPECT/CT (99mTc-HMPAO-WBC SPECT/CT) and [18F]FDG PET/CT imaging were calculated by using microbiology (n = 35) or clinical follow-up (n = 41) as final diagnosis. 99mTc-HMPAO-WBC scintigraphy and [18F]FDG PET/CT findings were compared with 95% CIs by using the McNemar test to those of echocardiography/CT, blood culture, and the Duke criteria. Results: Sensitivity, specificity, and accuracy of 99mTc-HMPAO-WBC were 86, 92, and 88%, respectively, with a slightly higher sensitivity for tube graft infection (TGI) as compared to isolated AV and combined AVTG. Overall, sensitivity, specificity, and accuracy of [18F]FDG PET/CT were 97, 73, and 90%, respectively. In 22 patients with suspected very early and early postsurgical infections, the two imaging modalities were concordant in 17 cases [10 true positive (TP) and 7 true negative (TN)]. [18F]FDG PET/CT presented a higher sensitivity than 99mTc-HMPAO-WBC scan. 99mTc-HMPAO-WBC scan correctly classified as negative three false-positive (FP) PET/CT findings. Conclusion: Our findings supported the use of 99mTc-HMPAO-WBC SPECT/CT and [18F]FDG PET/CT in patients with suspicion infection after the Bentall procedure early in the course of the disease onset to confirm the diagnosis and provide a comprehensive assessment of disease burden through the proposed criteria.

[18F]FMCH PET/CT biomarkers and similarity analysis to refine the definition of oligometastatic prostate cancer.

BACKGROUND: The role of image-derived biomarkers in recurrent oligometastatic Prostate Cancer (PCa) is unexplored. This paper aimed to evaluate [18F]FMCH PET/CT radiomic analysis in patients with recurrent PCa after primary radical therapy. Specifically, we tested intra-patient lesions similarity in oligometastatic and plurimetastatic PCa, comparing the two most used definitions of oligometastatic disease. METHODS: PCa patients eligible for [18F]FMCH PET/CT presenting biochemical failure after first-line curative treatments were invited to participate in this prospective observational trial. PET/CT images of 92 patients were visually and quantitatively analyzed. Each patient was classified as oligometastatic or plurimetastatic according to the total number of detected lesions (up to 3 and up to 5 or > 3 and > 5, respectively). Univariate and intra-patient lesions' similarity analysis were performed. RESULTS: [18F]FMCH PET/CT identified 370 lesions, anatomically classified as regional lymph nodes and distant metastases. Thirty-eight and 54 patients were designed oligometastatic and plurimetastatic, respectively, using a 3-lesion threshold. The number of oligometastic scaled up to 60 patients (thus 32 plurimetastatic patients) with a 5-lesion threshold. Similarity analysis showed high lesions' heterogeneity. Grouping patients according to the number of metastases, patients with oligometastatic PCa defined with a 5-lesion threshold presented lesions heterogeneity comparable to plurimetastic patients. Lesions within patients having a limited tumor burden as defined by three lesions were characterized by less heterogeneity. CONCLUSIONS: We found a comparable heterogeneity between patients with up to five lesions and plurimetastic patients, while patients with up to three lesions were less heterogeneous than plurimetastatic patients, featuring different cells phenotypes in the two groups. Our results supported the use of a 3-lesion threshold to define oligometastatic PCa.

Artificial intelligence and hybrid imaging: the best match for personalized medicine in oncology.

Artificial intelligence (AI) refers to a field of computer science aimed to perform tasks typically requiring human intelligence. Currently, AI is recognized in the broader technology radar within the five key technologies which emerge for their wide-ranging applications and impact in communities, companies, business, and value chain framework alike. However, AI in medical imaging is at an early phase of development, and there are still hurdles to take related to reliability, user confidence, and adoption. The present narrative review aimed to provide an overview on AI-based approaches (distributed learning, statistical learning, computer-aided diagnosis and detection systems, fully automated image analysis tool, natural language processing) in oncological hybrid medical imaging with respect to clinical tasks (detection, contouring and segmentation, prediction of histology and tumor stage, prediction of mutational status and molecular therapies targets, prediction of treatment response, and outcome). Particularly, AI-based approaches have been briefly described according to their purpose and, finally lung cancer-being one of the most extensively malignancy studied by hybrid medical imaging-has been used as illustrative scenario. Finally, we discussed clinical challenges and open issues including ethics, validation strategies, effective data-sharing methods, regulatory hurdles, educational resources, and strategy to facilitate the interaction among different stakeholders. Some of the major changes in medical imaging will come from the application of AI to workflow and protocols, eventually resulting in improved patient management and quality of life. Overall, several time-consuming tasks could be automatized. Machine learning algorithms and neural networks will permit sophisticated analysis resulting not only in major improvements in disease characterization through imaging, but also in the integration of multiple-omics data (i.e., derived from pathology, genomic, proteomics, and demographics) for multi-dimensional disease featuring. Nevertheless, to accelerate the transition of the theory to practice a sustainable development plan considering the multi-dimensional interactions between professionals, technology, industry, markets, policy, culture, and civil society directed by a mindset which will allow talents to thrive is necessary.

Miniaturized Radiochemical Purity Testing for 99mTc-HMPAO, 99mTc-HMDP, and 99mTc-Tetrofosmin.

Quick methods are functional in clinical practice to ensure the fastest availability of radiopharmaceuticals. For this purpose, we investigated the radiochemical purity of the widely used 99mTc-hydroxymethylene diphosphonate, 99mTc-hexamethylpropyleneamine oxime, and 99mTc-tetrofosmin by reducing time as compared with the manufacturer's method. Methods: We applied a miniaturized chromatographic method with a reduced strip development from 18 cm to 9 cm for all 3 radiopharmaceuticals. The specific support medium and solvent system of the manufacturer's methods was kept unchanged for 99mTc-hydroxymethylene diphosphonate and 99mTc-tetrofosmin, whereas for 99mTc-hexamethylpropyleneamine oxime the instant thin-layer chromatography (ITLC) polysilicic gel (silicic acid [SA]) was replaced with a monosilicic gel (silicic gel [SG]) in the chromatographic system that uses methyl ethyl ketone as solvent. The method was applied and compared with the routine ITLC insert method in a total of 30 batches for each radiopharmaceutical. The precision of repeated tests was determined by comparison with the results of 10 replications on the same batch. Small volumes of concentrated 99mTcO4-, and 99mTc-albumin nanocolloid were used to produce potential radiochemical impurities. Correlation between the quick methods and the insert methods was analyzed using a nonparametric 2-tailed test and a 2 × 2 contingency table with the associated Fisher exact test to evaluate sensitivity and specificity. A receiver-operating-characteristic analysis was performed to evaluate the best cutoff. Results: The percentage radiochemical purity of the quick methods agreed with the standard chromatography procedures. We found that 99mTcO4 and colloidal impurities are not the only common radiochemical impurities with 99mTc-tetrofosmin, and shortening of the ITLC strip with respect to the manufacturer's method will worsen system resolution and may produce inaccuracy. Conclusion: The miniaturized methods we described represent a fast and reliable alternative for 99mTc-exametazime and 99mTc-oxidronate quality control, with the upper cutoff for acceptable radiochemical purity values being 84% and 95%, respectively. For 99mTc-tetrofosmin radiochemical purity testing, a longer strip as described in the standard method is warranted.