351 Prevalence and prognostic significance of RV uptake (biventricular uptake) at planar scintigraphy in patients with ATTR cardiac amyloidosis

Aims The validation of cardiac scintigraphy with bone tracers for nonbiopsy confirmation of transthyretin cardiac amyloidosis (ATTR-CA) has revolutionized the diagnosis of this condition. While most studies focused on left ventricle (LV) uptake, the significance of bone tracers uptake in the right ventricle (RV) leading to biventricular (BiV) uptake has not been investigated so far. BiV uptake at planar scintigraphy might reflect a more advanced ATTR-CA. To estimate the prevalence of BiV uptake and its potential prognostic role in ATTR-CA. Methods and results Multicentre, retrospective, observational study performed among four Italian referral centres for CA. Data of ATTR-CA patients who underwent bone tracers scintigraphy with acquisition of planar and SPECT imaging between November 2014 and June 2020 at participating centres were centrally revised. ATTR-CA was diagnosed according to the Gilmore’s algorithm. LV uptake was assessed by Perugini visual scale. RV uptake was defined as: 0 = absent, 1 ≤ bone uptake, 2 = equal to bone uptake, and 3 ≥ bone uptake. Images were independently assessed by six experienced operators, blinded to all patients’ data. Cardiological data included clinical examination, ECG, echocardiography and blood tests. The primary outcome was a composite of cardiac death and hospitalization for heart failure. Of the 124 patients with ATTR-CA included in this analysis, 93 (75%) had BiV uptake at planar scintigraphy and all had RV free wall uptake confirmed at SPECT imaging. The prevalence of planar BiV uptake increased along with the LV Perugini grade: 14% in Perugini grade 1, 70% in Perugini grade 2, and 92% in Perugini grade 3. Compared to those with planar LV uptake, patients with planar BiV uptake were older (81 vs. 77 years, P = 0.006), more frequently in NYHA ≥3 (32% vs. 10%, P = 0.018), had increased NT-proBNP values (4293 vs. 2492 pg/ml, P = 0.046), LV wall thickness (18 vs. 17 mm, P = 0.007). They had higher rates of LV ejection fraction <50% (42% vs. 10%, P = 0.001) and lower TAPSE (16 vs. 20 mm, P = 0.048). At 18 months, patients with BiV uptake experienced the primary endpoint more frequently than those with LV uptake (P = 0.021, Figure), with the highest risk observed in patients with grade 2–3 RV uptake (P = 0.010). The LV Perugini grade did not affect prognosis (P = 0.20). At multivariate analysis, NYHA ≥3, eGFR <60 ml/min and BiV uptake had independent prognostic value (HR 8.0, P = 0.007; HR 2.1, P = 0.025; HR 1.7, P = 0.007; respectively). Conclusions The presence of BiV uptake at planar scintigraphy identified ATTR-CA patients at worse cardiovascular outcome, potentially serving as novel marker for prognostic stratification in this population.

Focal unspecific bone uptake on [18F]-PSMA-1007 PET: a multicenter retrospective evaluation of the distribution, frequency, and quantitative parameters of a potential pitfall in prostate cancer imaging

Purpose Improved logistics and availability led to a rapid increase in the use of [18F]-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 [18F]-PSMA-1007 PET. Methods We retrospectively analyzed [18F]-PSMA-1007 PET scans from four centers for the presence of UBU, defined as a focal mild-to-moderate uptake (SUVmax < 10.0) not obviously related to a benign or malignant cause. If present, up to three leading UBUs were quantified (SUVmax), 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 [18F]-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 [18F]-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.

Focal Unspecific Bone Uptake on [18F]-psma-1007 Pet: A Multicenter Retrospective Evaluation of the Distribution, Frequency, and Quantitative Parameters of a Potential Pitfall in Prostate Cancer Imaging

PurposeImproved logistics and availability led to a rapid increase in the use of [18F]-PSMA-1007 for prostate cancer PET imaging. Initial data suggests increased uptake in benign lesions compared to [68Ga]-PSMA-11, and clinical observations found increased unspecific bone uptake (UBU). We therefore investigate the frequency and characteristics of UBU in [18F]-PSMA-1007 PET.MethodsWe retrospectively analyzed [18F]-PSMA-1007 PET scans from four centers for the presence of UBU, defined as a focal mild-to-moderate uptake (SUVmax < 10.0) not obviously related to a benign or malignant cause. If present, up to three leading UBUs were quantified (SUVmax), 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.ResultsUBUs were identified in 179 out of 348 patients (65.2%). 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 [18F]-PSMA-1007 dose. UBUs were significantly more frequent in images obtained with digital scanners (70.1%) than analog scanners (p=.0001). 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 (43.1%), benign in 28 (43.1%), and malignant in nine (13.8%) patients.ConclusionUBUs occur in two-thirds of patients imaged with [18F]-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.

A Stepwise Approach to Identify the Clinical Role of FDG PET-CT in Patients with Suspicious Bone Metastasis from an Unknown Primary Site

Objectives: In patients with suspicious bone metastasis, differential diagnosis and primary lesion identification is very important in optimizing treatment planning. The study was aimed to assign a step-wise approach based on image findings to identify the precise role of PET-CT in these patients. Patients and Methods: A total of 74 patients were enrolled with suspicious bone metastasis who underwent PET-CT for the evaluation of primary focus. Patients were classified into four groups with stepwise manners, firstly based on FDG positivity of bone lesions, then on multiplicity of positive bone uptake and finally on presence of extra-skeletal uptake. We analyzed the difference of distribution of follow-up results according to each group. In addition, we also investigated whether PET-CT had a role to guide biopsy sites. Results: Except for 7 patients without bone or extra-skeletal uptake, 44 patients were categorized in multiple bone and extra-skeletal uptake group (A), 12 in multiple bone uptake without extra-skeletal uptake group (B), 3 in single bone and extra-skeletal uptake group (C) and 8 in single bone uptake without extra-skeletal uptake group (D). In group A, 42/44 patients had metastatic bone disease; where primary lesion was correlating extra-skeletal uptake in 40 (91.0%) cases. Among the 12 patients of group B, 5 (41.7%) had primary malignant bone disease, 3 (25.0%) had benign bone lesions and 4 (33.3%) had metastatic bone disease but PET-CT failed to indicate the primary site. In group C, PET-CT positive extra-skeletal uptake sites were confirmed as primary lesions in all the 3 patients. Among the 8 patients of group D, 5 (62.5%) were benign bone disease, one (12.5%) was high grade sarcoma and the remaining two (25.0%) were metastatic bone disease where PET-CT failed to identify primary site. Additionally, there was significant (P = 0.0003) difference in prevalence of biopsy sites performed according to the presence of extra-skeletal uptake in PET-CT. Conclusion: Clinical impact of PET-CT was different according to groups classified with stepwise manners, which suggested that different strategies should be taken especially when there was not extra-skeletal uptake to optimize management plan. PET-CT also had a significant role in patients with extra-skeletal uptake lesion through guidance of easily approachable biopsy sites. Bangladesh J. Nuclear Med. 22(2): 95-102, Jul 2019

Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

Recently, a 18F-labeled derivative of the widely used 68Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although 18F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with 18F-PSMA-11 or 68Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received ± 3.7 MBq 18F-PSMA-11 and 68Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq 18F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUVmean, SUVmax, TBRmean and TBRmax). Mice underwent ex vivo biodistribution where 18F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (Kd) of 18F-PSMA-11 and 68Ga-PSMA-11 was 2.95 ± 0.87 nM and 0.49 ± 0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both 18F-PSMA-11 and 68Ga-PSMA-11, while no difference was found for 18F-FDG uptake (except for SUVmax). Tumor uptake of 18F-PSMA-11 showed a similar trend over time as 68Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBRmean and TBRmax were significantly higher at the later timepoint, as well as the SUVmax of 68Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0 ± 13.6%ID/g 1 h p.i.) and the bladder (6.48 ± 2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for 18F-PSMA-11 compared to 68Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late 18F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of 18F-PSMA-11 as well as no significant increase in bone uptake.

18F-sodium fluoride bone deposition quantitation with PET in Mice: Variation with age, sex, and circadian rhythm

Aim The aim of this study was to establish a data base for normal 18F-sodium fluoride (18F-NaF) bone uptake as a function of age, sex and circadian rhythm in mice. Methods In 12 female (F) and 12 male (M) C57BL/6N mice PET images were acquired 90 min after intravenous injection of 20 MBq 18F-NaF for 30 minutes. Each mouse was imaged in follow-up studies at 1, 3, 6, 13 and 21 months of age. In order to assess for physiologic changes related to circadian rhythm, animals were imaged during light (sleep phase) as well as during night conditions (awake phase). Bone uptake is described as the median percentage of the injected activity (%IA) and in relation to bone volume (%IA/ml). Results A significant smaller bone volume was found in F (1.79 ml) compared to M (1.99 ml; p < 0.001). In sex-pooled data, highest bone uptake occurred at an age of 1 month (61.1 %IA, 44.5 %IA/ml) with a significant reduction (p < 0.001) at age 3 months (43.6 %IA, 23.6 %IA/ml), followed by an increase between 13 (47.3 %IA, 24.5 %IA/ml) and 21 months (52.2 %IA, 28.1 %IA/ml). F had a significantly higher total uptake (F 48.2 %IA, M 43.8 %IA; p = 0.026) as well as a higher uptake per ml bone tissue (F 27.0 %IA/ml; M 22.4 %IA/ml; p < 0.001). A significant impact of circadian rhythm was only found for F at ages of 3 and 6 months with a higher uptake during the sleep phase. Conclusion Circadian rhythm had a significant impact on uptake only in F of 3 and 6 months. Regarding sex, F showed generally higher uptake rates than M. The highest uptake values were observed during bone growth at age 1 month in both sexes, a second uptake peak occurred in elderly F. Designing future bone uptake studies with M, attention must be paid to age only, while in F circadian rhythm and age must be taken into account.