Pilot Feasibility Study: 18 F-DPA-714 PET/CT Macrophage Imaging in Triple-Negative Breast Cancers (EITHICS).

ABSTRACT: Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18 F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism. PATIENTS AND METHODS: Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18 F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3 H-DPA-714, and 3 H-PK-11195 autoradiography were conducted. RESULTS: The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%-94%). 18 F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18 F-DPA-714 TACs were identified, categorized as "above muscular," "equal to muscular," and "below muscular" with reference to the muscular background. For the "above muscular" group (2 HAB and 2 MAB), "equal muscular" group (3 HAB, 3 MAB, and 1 LAB), and "below muscular" group (1 LAB and 1 MAB), tumor TACs showed a 18 F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUV mean of 4.02 (2.09-5.31), 1.66 (0.93-3.07), and 0.61 (0.43-1.02). CONCLUSIONS: This study successfully demonstrated TNBC tumor targeting by 18 F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker.

Between Pathological Prostate Cancer Lymph Nodes and Sentinel Nodes: Which Information Is the Leader?

PURPOSE: On the basis of the concept of sentinel lymph node biopsy (SLNB), SLNs should contain decisive information for clinical outcomes. In localized prostate cancer patients, this study assessed retrospectively clinical outcome after radical laparoscopic prostatectomy associated with SLNB and extensive pelvic lymph node dissection. METHODS: A total of 231 consecutive patients of intermediate to high risk were analyzed. Recurrence-free survival (RFS) was assessed with Kaplan-Meier curves. Various pathological parameters were analyzed using univariable and multivariable analyses through Cox regression analysis. The study was approved and registered under 2007-R41. RESULTS: The median follow-up was 7.1 years (95% confidence interval, 6.6-7.5). In total, 38/231 (16.5%) patients were pN1. Of these 38 patients, 27 had only SLN involvement (SLNI), 10 patients had both SLN and non-SLNI, and 1 patient had isolated non-SLNI, indicating a false-negative (FN). If the updated Briganti nomogram threshold set at >7% for recommending extensive pelvic lymph node dissection had been applied to these patients, we would have missed 44% (12/27) of patients with SLNI and 50% (5/10) of patients with SLNI and non-SLNI, as well as the FN patient. At the time of final follow-up, 84/231 (36.5%) patients had recurrence. In multivariable analysis, and regarding node status, the most significant prognostic factor was SLN with macrometastases and/or micrometastases, respectively, P = 10-3 and P < 10-3. No more information was obtained with non-SLN status. Probabilities of RFS between negative and positive SLN patients presented a major significant difference (P < 10-15) with a risk of event 8.75 times more frequent if SLN was involved than if it was metastasis-free. CONCLUSIONS: SLNB seems to contain decisive information for the clinical outcome of patients with localized intermediate- and high-risk prostate cancer patients. The question raised is thus whether immediate additional postoperative treatment should be offered to patients with metastatic SLN.

Long-term Trace of Radiation Pneumonitis With 18F-Fluoroestradiol.

Radiation pneumonitis (RP) can be an adverse complication of radiotherapy and usually occurs as an acute reaction from 6 to 12 weeks after radiotherapy. FDG PET is described as an early and adequate barometer for RP diagnosis. Only 1 case of fluoroestradiol uptake contemporary of metabolic FDG changes attributed to RP is reported. We report a case of a breast cancer patient with asymptomatic RP, who at 1 year later, at sequelar stage on CT, showed long-term memory of RP by F-fluoroestradiol PET imaging with nonmetabolic FDG PET.

Preliminary results of a 68 Ga-PSMA PET/CT prospective study in prostate cancer patients with occult recurrence: Diagnostic performance and impact on therapeutic decision-making.

BACKGROUND: In this prospective study (NCT03443609), we investigated the impact of 68Ga-PSMA-11 PET-CT on the treatment plan and therapeutic response obtained for patients with prostate cancer (PCa) presenting a recurrence with a low rising PSA. METHODS: One hundred thirty hormone-naive (PSA < 1.5 ng/mL) patients were enrolled. All patients received radical treatment. PET images were recorded 1 and 2 hours after injection of tracer and interpreted by two independent nuclear physicians. Six months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results. RESULTS: Data analysis for the first 52 included patients has been completed. 68Ga-PSMA-11-positive lesions were detected in 38/52 (73.1%) patients. Ninety-four lesions were detected as follows, 53/94 in lymph nodes (56.4%), 25/94 in bone (26.6%), and 12/94 into the prostate bed (12.7%). Detection rates were 58%, 81%, and 82% for serum PSA levels lower than 0.25 ng/mL, between 0.25 to ≤ 0.69 ng/mL and 0.70 ng/mL, respectively. As a result of the PSMA PET-CT, therapeutic management changed in 38/52 patients (73.1%). Patients had undetectable serum PSA levels after treatment guided by 68Ga-PSMA-11 PET-CT results in 10/52 (19.2%) cases and with a PSA decrease of over 60% in 18/52 (34.6%) patients. CONCLUSION: Whilst our patient population presented a very low PSA level, preliminary results of the 68Ga-PSMA PET-CT study showed recurrence localization in more than half of the patients and this had a major clinical impact, as it resulted in treatment change in more than half of the patients and a significant decrease in PSA levels in a third of patients.

68Ga-PSMA-11 PET-CT study in prostate cancer patients with biochemical recurrence and non-contributive 18F-Choline PET-CT: Impact on therapeutic decision-making and biomarker changes.

BACKGROUND: In this retrospective study, we investigated the impact of 68 Ga-PSMA-11 PET-CT (PSMA PET-CT) upon the treatment plan and therapeutic response obtained for Prostate Cancer (PCa) patients presenting an occult biochemical recurrence. METHODS: Forty-two patients with previously negative or doubtful 18F-Choline (FCH) were enrolled. PET images were recorded 1 h after injection of tracer. Only a few months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results. RESULTS: PSMA-positive lesions were detected in 34/42 (80.9%) patients. Detection rates were 85.7% and 89.3% for serum PSA levels lower than 2 ng/mL, and >2 ng/mL, respectively. One hundred seventy-three lesions were detected: 132/173 in lymph nodes (76.3%), 22/173 as metastatic sites (bone or lung) (12.7%), and 19/173 in the prostate bed (10.9%). As a result of the PSMA PET-CT, therapeutic management changed in 31/42 patients (73.8%). With a follow-up of 4.9 ± 2.27 months, 32/42 (76.2%) PSA assays after treatment guided by PSMA PET-CT were collected. For 37.5% (12/32) of patients, the serum PSA level was lower than 0.2 ng/mL and a PSA decrease of over 50% in 8 (25.0%) other patients were obtained. CONCLUSION: Performing a PSMA PET-CT when FCH PET-CT was doubtful or negative allows the recurrence localization in more 80% of patients and this had a major clinical impact, as it resulted in treatment change in more than 70% of patients as well as a significant decrease in PSA levels in more than 60% of them.

Additional value of combining low-dose computed tomography to V/Q SPECT on a hybrid SPECT-CT camera for pulmonary embolism diagnosis.

OBJECTIVES: The aim of the study was to assess the potential interest of combining a low-dose computed tomography (ldCT) to ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT) for the diagnosis of pulmonary embolism (PE). We addressed three main questions: Could ldCT be used in substitution to ventilation SPECT? Could ldCT improve the diagnostic performance of V/Q SPECT? Could ldCT provide alternative diagnoses to PE? METHODS: A total of 393 patients previously analysed in a management outcome study that aimed at assessing the safety of V/Q SPECT for PE diagnosis were assessed. All patients underwent an ldCT under the same SPECT-computed tomography camera, which was not used at the time of initial interpretation. Three retrospective analyses were performed: Q SPECT combined with ldCT, V/Q SPECT combined with ldCT and ldCT only. RESULTS: On the basis of initial V/Q SPECT interpretation, 110 (28%) patients were positive and 283 (72%) were negative for PE.With Q SPECT-ldCT, 139 (35%) patients were positive and 254 (65%) were negative, with 55 (19%) discrepancies when compared with V/Q SPECT. Of the 283 patients with negative V/Q SPECT, 42 were positive with V/Q SPECT-ldCT, and among the 110 patients with positive V/Q SPECT 13 were negative with V/Q SPECT-ldCT. On using V/Q SPECT-ldCT, 97 (25%) patients were positive and 296 (75%) were negative, with 13 (3%) discrepancies when compared with V/Q SPECT (all had had a positive V/Q SPECT but a negative V/Q SPECT-ldCT). Finally, 67 (24%) ldCT scans showed a potential alternative diagnosis to PE. CONCLUSION: For PE diagnosis with lung SPECT, the use of ldCT in substitution to ventilation SPECT is associated with a high risk of overdiagnosis. The diagnostic value of ldCT in addition to V/Q SPECT remains unclear. Further studies are needed to determine its potential role in PE diagnosis.