Multimodality Imaging of Prostate Cancer Ghafoor, Soleen; Burger, Irene A; Vargas, Alberto H
Journal of Nuclear Medicine,
10/2019, Letnik:
60, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Prostate cancer is a very heterogeneous disease, and contemporary management is focused on identification and treatment of the prognostically adverse high-risk tumors while minimizing overtreatment ...of indolent, low-risk tumors. In recent years, imaging has gained increasing importance in the detection, staging, posttreatment assessment, and detection of recurrence of prostate cancer. Several imaging modalities including conventional and functional methods are used in different clinical scenarios with their very own advantages and limitations. This continuing medical education article provides an overview of available imaging modalities currently in use for prostate cancer followed by a more specific section on the value of these different imaging modalities in distinct clinical scenarios, ranging from initial diagnosis to advanced, metastatic castration-resistant prostate cancer. In addition to established imaging indications, we will highlight some potential future applications of contemporary imaging modalities in prostate cancer.
While RECIST 1.1 is well established in radiological response assessment, it is of limited use in prostate cancer (PCa) considering that the disease is often seen only as sclerotic bone changes on ...conventional imaging. Therefore, a molecular imaging-based response assessment including bone scans has been proposed and used in clinical trials, however, due to the flare phenomenon on bone scans this assessment leads to substantial delays in the detection of progression. Indeed, a robust and reliable imaging tool to assess response to chemotherapy in PCa is still warranted. Whether Positron Emission Tomography (PET) targeting the Prostate-Specific Membrane Antigen (PSMA) could achieve this, is still controversial. In this review, we summarized the available data on cytotoxic agents and their impact on PSMA expression, as well as the available data on PSMA PET imaging for response assessment.
Human brown adipose tissue (BAT) is a thermogenic tissue activated by the sympathetic nervous system in response to cold exposure. It contributes to energy expenditure (EE) and takes up glucose and ...lipids from the circulation. Studies in rodents suggest that BAT contributes to the transient rise in EE after food intake, so-called diet-induced thermogenesis (DIT). We investigated the relationship between human BAT activity and DIT in response to glucose intake in 17 healthy volunteers. We assessed DIT, cold-induced thermogenesis (CIT), and maximum BAT activity at three separate study visits within 2 wk. DIT was measured by indirect calorimetry during an oral glucose tolerance test. CIT was assessed as the difference in EE after cold exposure of 2-h duration as compared with warm conditions. Maximal activity of BAT was assessed by 18-F-fluoro-deoxyglucose (
F-FDG)
F-FDG-PET/MRI after cold exposure and concomitant pharmacological stimulation with mirabegron. Seventeen healthy men (mean age = 23.4 yr, mean body mass index = 23.2 kg/m
) participated in the study. EE increased from 1,908 (±181) kcal/24 h to 2,128 (±277) kcal/24 h (
< 0.0001, +11.5%) after mild cold exposure. An oral glucose load increased EE from 1,911 (±165) kcal/24 h to 2,096 (±167) kcal/24 h at 60 min (
< 0.0001, +9.7%). The increase in EE in response to cold was significantly associated with BAT activity (
= 0.43,
= 0.004). However, DIT was not associated with BAT activity (
= 0.015,
= 0.64). DIT after an oral glucose load was not associated with stimulated
F-FDG uptake into BAT, suggesting that DIT is independent from BAT activity in humans (Clinicaltrials.gov Registration No. NCT03189511).
Cold-induced thermogenesis (CIT) was related to BAT activity as determined by FDG-PET/MRI after stimulation of BAT. Diet-induced thermogenesis (DIT) was not related to stimulated BAT activity. Supraclavicular skin temperature was related to CIT but not to DIT. DIT in humans is probably not a function of BAT.
Purpose
Accurate attenuation correction (AC) is essential for quantitative analysis of PET tracer distribution. In MR, the lack of cortical bone signal makes bone segmentation difficult and may ...require implementation of special sequences. The purpose of this study was to evaluate the need for accurate bone segmentation in MR-based AC for whole-body PET/MR imaging.
Methods
In 22 patients undergoing sequential PET/CT and 3-T MR imaging, modified CT AC maps were produced by replacing pixels with values of >100 HU, representing mostly bone structures, by pixels with a constant value of 36 HU corresponding to soft tissue, thereby simulating current MR-derived AC maps. A total of 141 FDG-positive osseous lesions and 50 soft-tissue lesions adjacent to bones were evaluated. The mean standardized uptake value (SUVmean) was measured in each lesion in PET images reconstructed once using the standard AC maps and once using the modified AC maps. Subsequently, the errors in lesion tracer uptake for the modified PET images were calculated using the standard PET image as a reference.
Results
Substitution of bone by soft tissue values in AC maps resulted in an underestimation of tracer uptake in osseous and soft tissue lesions adjacent to bones of 11.2 ± 5.4 % (range 1.5–30.8 %) and 3.2 ± 1.7 % (range 0.2–4 %), respectively. Analysis of the spine and pelvic osseous lesions revealed a substantial dependence of the error on lesion composition. For predominantly sclerotic spine lesions, the mean underestimation was 15.9 ± 3.4 % (range 9.9–23.5 %) and for osteolytic spine lesions, 7.2 ± 1.7 % (range 4.9–9.3 %), respectively.
Conclusion
CT data simulating treating bone as soft tissue as is currently done in MR maps for PET AC leads to a substantial underestimation of tracer uptake in bone lesions and depends on lesion composition, the largest error being seen in sclerotic lesions. Therefore, depiction of cortical bone and other calcified areas in MR AC maps is necessary for accurate quantification of tracer uptake values in PET/MR imaging.
Purpose
Improved logistics and availability led to a rapid increase in the use of
18
F-PSMA-1007 for prostate cancer PET imaging. Initial data suggests increased uptake in benign lesions compared to ...
68
Ga-PSMA-11, and clinical observations found increased unspecific bone uptake (UBU). We therefore investigate the frequency and characteristics of UBU in
18
F-PSMA-1007 PET.
Methods
We retrospectively analyzed
18
F-PSMA-1007 PET scans from four centers for the presence of UBU, defined as a focal mild-to-moderate uptake (SUV
max
< 10.0) not obviously related to a benign or malignant cause. If present, up to three leading UBUs were quantified (SUV
max
), localized, and correlated to clinical parameters, such as age, PSA, injected dose, Gleason score, tumor size (T1–T4), and type of PET scanner (analog vs. digital). Additionally, clinical and imaging follow-up results and therapeutic impact were evaluated.
Results
UBUs were identified in 179 out of 348 patients (51.4%). The most frequent localizations were ribs (57.5%) and pelvis (24.8%). The frequency of UBUs was not associated with PSA, Gleason score, tumor size, age, or the injected
18
F-PSMA-1007 dose. UBUs were significantly more frequent in images obtained with digital PET/CT scans (n = 74, 82%) than analog PET/CT scans (n = 221, 40.3%) (
p
= .0001) but not in digital PET/MR (n = 53, 51%) (
p
= .1599). In 80 out of 179 patients (44.7%), the interpretation of UBUs was critical for therapeutic management and therefore considered clinically relevant. For 65 UBUs, follow-ups were available: three biopsies, three radiotherapies with PSA follow-up, and 59 cases with imaging. After follow-up, UBUs were still considered unclear in 28 of 65 patients (43%), benign in 28 (43%), and malignant in nine (14%) patients.
Conclusion
UBUs occur in two-thirds of patients imaged with
18
F-PSMA-1007 PET/CT and are significantly more frequent on digital PET scanners than analog scanners. UBUs should be interpreted carefully to avoid over-staging.
Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be ...a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful to further improve the detection rate of PSMA-based imaging. To achieve this, we tested dutasteride (Duta)-generally used for treatment of benign prostatic enlargement-and lovastatin (Lova)-a compound used to reduce blood lipid concentrations. We aimed to compare the individual effects of Duta and Lova on cell proliferation as well as PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. Our results show that a treatment with ≤1 μM Duta and ≥1 μM Lova lead to a significant upregulation of whole and cell surface PSMA expression in LNCaP, C4-2 and VCaP cells. Lower concentrations of Duta and Lova in combination (0.5 μM Duta + 0.5 μM Lova or 0.5 μM Duta + 1 μM Lova) were further capable of enhancing PSMA protein expression compared to a single compound treatment using higher concentrations in all tested cell lines (LNCaP, C4-2 and VCaP).
Brown adipose tissue (BAT) is a specialized form of adipose tissue, able to increase energy expenditure by heat generation in response to various stimuli. Recently, its pathological activation has ...been implicated in the pathogenesis of cancer cachexia. To establish a causal relationship, we retrospectively investigated the longitudinal changes in BAT and cancer in a large FDG-PET/CT cohort. We retrospectively analyzed 13 461 FDG-PET/CT examinations of n = 8 409 patients at our institution from the winter months of 2007-2015. We graded the activation strength of BAT based on the anatomical location of the most caudally activated BAT depot into three tiers, and the stage of the cancer into five general grades. We validated the cancer grading by an interreader analysis and correlation with histopathological stage. Ambient temperature data (seven-day average before the examination) was obtained from a meteorological station close to the hospital. Changes of BAT, cancer, body mass index (BMI) and temperature between the different examinations were examined with Spearman's test and a mixed linear model for correlation, and with a causal inference algorithm for causality. We found n = 283 patients with at least two examinations and active BAT in at least one of them. There was no significant interaction between the changes in BAT activation, cancer burden or BMI. Temperature changes exhibited a strong negative correlation with BAT activity (ϱ = -0.57, p<0.00001). These results were confirmed with the mixed linear model. Causal inference revealed a link of Temperature â BAT in all subjects and also of BMI â BAT in subjects who had lost weight and increased cancer burden, but no role of cancer and no causal links of BAT â BMI. Our data did not confirm the hypothesis that BAT plays a major role in cancer-mediated weight loss. Temperature changes are the main driver of incidental BAT activity on FDG-PET scans.
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