Combined forced diuresis and late acquisition on [68Ga]Ga-PSMA-11 PET/CT for biochemical recurrent prostate cancer: a clinical practice-oriented study.

OBJECTIVES: Increased detection of prostate cancer (PCa) recurrences using [68Ga]Ga-PSMA-11 PET/CT has been reported by adding forced diuresis or late-phase imaging to the standard protocol. However, the combination of these procedures in the clinical setting is still not standardized. METHODS: One hundred prospectively recruited biochemical recurrent PCa patients were restaged with dual-phase [68Ga]Ga-PSMA-11 PET/CT from September 2020 to October 2021. All patients received a standard scan (60 min), followed by diuretics (140 min) and a late-phase abdominopelvic scan (180 min). PET readers with low (n = 2), intermediate (n = 2), or high (n = 2) experience rated (i) standard and (ii) standard + forced diuresis late-phase images in a stepwise fashion according to E-PSMA guidelines, scoring their level of confidence. Study endpoints were (i) accuracy against a composite reference standard, (ii) reader's confidence level, and (iii) interobserver agreement. RESULTS: Forced diuresis late-phase imaging increased the reader's confidence category for local and nodal restaging (both p < 0.0001), and the interobserver agreement in identifying nodal recurrences (from moderate to substantial, p < 0.01). However, it significantly increased diagnostic accuracy exclusively for local uptakes rated by low-experienced readers (from 76.5 to 84%, p = 0.05) and for nodal uptakes rated as uncertain at standard imaging (from 68.1 to 78.5%, p < 0.05). In this framework, SUVmax kinetics resulted in an independent predictor of PCa recurrence compared to standard metrics, potentially guiding the dual-phase PET/CT interpretation. CONCLUSIONS: The present results do not support the systematic combination of forced diuresis and late-phase imaging in the clinical setting, but allow the identification of patients-, lesions-, and reader-based scenarios that might benefit from it. KEY POINTS: • Increased detection of prostate cancer recurrences has been reported by adding diuretics administration or an additional late abdominopelvic scan to the standard [68Ga]Ga-PSMA-11 PET/CT procedure. • We verified the added value of combined forced diuresis and delayed imaging, showing that this protocol only slightly increases the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET/CT, thus not justifying its systematic use in clinics. • However, it can be helpful in specific clinical scenarios, e.g., when PET/CT is reported by low-experienced readers. Moreover, it increased the reader's confidence and the agreement among observers.

Cumulative radiation doses due to nuclear medicine examinations: a systematic review.

OBJECTIVES: To systematically review the published data regarding the cumulative exposure to radiation in selected cohorts of adults or paediatric patients due to diagnostic nuclear medicine examinations. METHODS: We conducted PubMed/Medline searches of peer-reviewed papers on cumulated effective dose (CED) from diagnostic nuclear medicine procedures published between 01 January 2010 until 31 January 2021. Studies were considered eligible if the contribution of nuclear medicine examinations to total CED was >10%. Studies reporting cumulative doses in a single episode of care or in a limited time (≤1 year) were excluded. The main outcomes for which data were sought were the CED accrued by patients, the period in which the CED was accrued, the percentage of patients with CED > 100 mSv and the percentage contribution due to nuclear medicine procedures to the overall CED. RESULTS: The studies included in the synthesis were 18 which enrolled a total of 1,76,371 patients. Eleven (1,757 patients), three (1,74,079 patients) and four (535 patients) were related to oncological, cardiologic and transplanted patients, respectively. All the studies were retrospective; some of the source materials referred to small number of patients and some of the patients were followed for a short time. Not many studies accurately quantified the contribution of nuclear medicine procedures to the overall radiation exposure due to medical imaging. Finally, most of the studies covered an observation period which extended mainly in the 2000-2010 decade. CONCLUSIONS: There is a need of prospective, multicentric studies enrolling a greater number of patients, followed for longer period in selected groups of patients to fully capture the cumulative exposure to radiation in these settings. ADVANCES IN KNOWLEDGE: This systematic review allows to identify selected group of patients with a specific health status in which the cumulated exposure to radiation may be of concern and where the contribution of nuclear medicine procedures to the total CED is significant.

Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study.

PURPOSE: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. METHODS: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. RESULTS: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). CONCLUSIONS: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

The Challenge of Evaluating Response to Peptide Receptor Radionuclide Therapy in Gastroenteropancreatic Neuroendocrine Tumors: The Present and the Future.

The NETTER-1 study has proven peptide receptor radionuclide therapy (PRRT) to be one of the most effective therapeutic options for metastatic neuroendocrine tumors (NETs), improving progression-free survival and overall survival. However, PRRT response assessment is challenging and no consensus on methods and timing has yet been reached among experts in the field. This issue is owed to the suboptimal sensitivity and specificity of clinical biomarkers, limitations of morphological response criteria in slowly growing tumors and necrotic changes after therapy, a lack of standardized parameters and timing of functional imaging and the heterogeneity of PRRT protocols in the literature. The aim of this article is to review the most relevant current approaches for PRRT efficacy prediction and response assessment criteria in order to provide an overview of suitable tools for safe and efficacious PRRT.

Somatostatin receptors over-expression in castration resistant prostate cancer detected by PET/CT: preliminary report of in six patients.

Prostate cancer (PC) is usually characterized by an excellent prognosis, largely due to little biological aggressiveness and the power of hormonal deprivation therapy. In spite of these favorable characteristics, however, a significant quota of patients does not respond to androgen deprivation therapy (ADT) and develop a progressive disease. Castration-resistant prostate cancer (CRPC) is defined by disease progression in spite of ADT. This progression may show any combination of a rise in serum prostate-specific antigen (PSA), clinical and radiological progression of pre-existing disease, and appearance of new metastases. This event is a striking change in the clinical scenario, since the power of treatment for CRPC patients with distant metastases is very limited. Somatostatin is a hormone produced by neuroendocrine cells. Its distant effects are mediated by the binding to five specific receptors, which are the most striking parameter for neuroendocrine. Various synthetic somatostatin agonists able to bind to the receptors have been synthesized during the past two decades for diagnostic and therapeutic purposes. Octreotide, the most popular of these, is widely used to treat patients affected by neuroendocrine tumors. A number of researches carried out in the past evaluated the possible neuroendocrine differentiation (NED) of PC cells in the castration resistant phase. If proved, the presence of a specific class of receptor on cell's surfaces should give a potentially biological target to be used for therapy. However, these studies led to contradictory results. Aim of our phase III diagnostic trial was to study "in vivo" the over-expression of somatostatin receptors (SSTRs) in CRPC patients by PET/CT after the administration of the somatostatin analog [(68)Ga-DOTANOC,1-Nal(3)]-octreotide labeled with (68)Ga. Every area of increased uptake corresponding to a metastasis detected with other methods was considered as SSTRs expressing. False positivity to SSTRs expression was considered those localizations with a suspicious uptake not confirmed by other radiologic procedures. On the other hand, metastatic lesions lacking the radiopharmaceutical's uptake were considered not SSTRs expressing metastases. The preliminary results in 6 of the 67 patients scheduled by our phase III trial showed metastases with a variable SSTRs expression in 2 patients.

Somatostatin Receptors in an Anaplastic Oligodendroglioma Relapse Evidenced By 68Ga DOTANOC PET/CT.

Six years ago, a right frontal lobe anaplastic oligodendroglioma negative for AE1/AE3 and HBM-45, positive for 1p/19q deletion, EMA, GFAP, and synaptophysin was excised from a 50-year-old woman. Treatments that followed were radiation therapy, and surgery plus radiation therapy and temozolomide for a relapse with an early partial response, followed by disease progression. In the middle of last year, 68Ga-DOTANOC PET/CT was carried out to evaluate the possibility of treatment with peptide receptor radionuclide therapy. The examination revealed a grossly round-shaped uptake corresponding to the surgical wall, with some smaller uptakes disseminated in different parts of the brain.

Neuroendocrine Differentiation of Prostate Cancer Metastases Evidenced "in Vivo" by 68Ga-DOTANOC PET/CT: Two Cases.

Prostate cancer is the second most commonly diagnosed neoplasm in men. This neoplasm has usually excellent prognosis, mostly consequent to the early diagnosis and the effective hormonal therapy. However, significant percentages of patients treated with total androgen blockade therapy, escape to treatment and evolve toward a more aggressive type of cancer. This clinical entity, named castration-resistant prostate cancer, has few and less effective therapeutic opportunities. Therefore, any additional information concerning possible biological targets to therapy is welcome. Here we describe two cases in which 68Ga-DOTANOC PET/CT evidenced the somatostatin receptor overexpression by prostate metastases. The presence of these receptors may support with a more strong evidence the possibility to administer somatostatin analogs as an adjuvant therapy.