18F-NaF/223RaCl2 theranostics in metastatic prostate cancer: treatment response assessment and prediction of outcome.
Ontology highlight
ABSTRACT:
SUBMITTER: Jadvar H
PROVIDER: S-EPMC6475949 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
<sup>18</sup>F-NaF/<sup>223</sup>RaCl<sub>2</sub> theranostics in metastatic prostate cancer: treatment response assessment and prediction of outcome.
Jadvar Hossein H Colletti Patrick M PM
The British journal of radiology 20180416 1091
Theranostics refers to companion agents with identical or similar structure targeted to a specific biological entity for imaging and treatment. Although the concept has a long history with radioiodine in thyroidology, but it has experienced remarkable recent renaissance in management of neuroendocrine tumors and prostate cancer. Bone scintigraphy based on osteoblastic reaction and targeted radionuclide therapy with the alpha-particle calcium-mimetic agent, <sup>223</sup>RaCl<sub>2</sub>, also fo ...[more]
Similar Datasets
Project description:BackgroundBone flare has been observed on 99mTc-MDP bone scans of patients with metastatic castration-resistant prostate cancer (mCRPC). This exploratory study investigates bone flare in mCRPC patients receiving androgen receptor (AR) inhibitors using 18F-NaF PET/CT.MethodsTwenty-nine mCRPC patients undergoing AR-inhibiting therapy (abiraterone, orteronel, enzalutamide) received NaF PET/CT scans at baseline, week 6, and week 12 of treatment. SUV metrics were extracted globally for each patient (SUV) and for each individual lesion (iSUV). Bone flare was defined as increasing SUV metrics or lesion number at week 6 followed by subsequent week 12 decrease. Differences in metrics across timepoints were compared using Wilcoxon tests. Cox proportional hazard regression was conducted between global metrics and progression-free survival (PFS).ResultsTotal SUV was most sensitive for flare detection and was identified in 14/23 (61%) patients receiving CYP17A1-inhibitors (abiraterone, orteronel), and not identified in any of six patients receiving enzalutamide. The appearance of new lesions did not account for initial increases in SUV metrics. iSUV metrics followed patient-level trends: bone flare positive patients showed a median of 72% (range: 0-100%) of lesions with total iSUV flare. Increasing mean SUV at week 6 correlated with extended PFS (HR = 0.58, p = 0.02).ConclusionNaF PET bone flare was present on 61% of mCRPC patients in the first 6 weeks of treatment with CYP17A1-inhibitors. Characterization provided in this study suggests favorable PFS in patients showing bone flare. This characterization of NaF flare is important for guiding treatment assessment schedules to better distinguish between patients showing bone flare and those truly progressing, and should be performed for all emerging mCRPC treatments and imaging agents.
| S-EPMC7490782 | biostudies-literature
Project description:Accumulating preclinical and clinical evidence suggests that calcification is one of the body's primary responses to injury and a key pathological feature of cardiovascular disease. Calcification activity can now be imaged using 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) in combination with either computed tomography or magnetic resonance. These techniques allow visualization of calcification activity and, therefore, provide different information to the established macroscopic calcium imaged with computed tomography. Indeed, 18F-NaF PET has been used to investigate a wide range of valvular conditions, including aortic stenosis, mitral annular calcification, and bioprosthetic valve disease, as well as vascular conditions, including abdominal aortic aneurysm disease, coronary, and carotid atherosclerosis, peripheral vascular disease, and erectile dysfunction. In this brief review, we will focus on how 18F-NaF PET has improved our pathophysiological understanding of cardiovascular calcification and how it can be used as a marker of vascular calcification, providing a useful tool that can be utilized in clinical trials investigating the prediction of both disease progression and clinical events. Finally, we will discuss how 18F-NaF might be employed clinically to improve patient assessment and to guide decision-making.
| S-EPMC7310305 | biostudies-literature
Project description:Fibrous dysplasia (FD) is a mosaic skeletal disorder resulting in fractures, deformity, and functional impairment. Clinical evaluation has been limited by a lack of surrogate endpoints capable of quantitating disease activity. The purpose of this study was to investigate the utility of 18 F-NaF PET/CT imaging in quantifying disease activity in patients with FD. Fifteen consecutively evaluated subjects underwent whole-body 18 F-NaF PET/CT scans, and FD burden was assessed by quantifying FD-related 18 F-NaF activity. 18 F-NaF PET/CT parameters obtained included (i) SUVmax (standardized uptake value [SUV] of the FD lesion with the highest uptake); (ii) SUVmean (average SUV of all 18 F-NaF-positive FD lesions); (iii) total volume of all 18 F-NaF-positive FD lesions (TV); and (iv) total FD lesion activity determined as the product of TV multiplied by SUVmean (TA = TV × SUVmean ) (TA). Skeletal outcomes, functional outcomes, and bone turnover markers were correlated with 18 F-NaF PET/CT parameters. TV and TA of extracranial FD lesions correlated strongly with skeletal outcomes including fractures and surgeries (p values ≤ 0.003). Subjects with impaired ambulation and scoliosis had significantly higher TV and TA values (P < 0.05), obtained from extracranial and spinal lesions, respectively. Craniofacial surgeries correlated with TV and TA of skull FD lesions (P < 0.001). Bone turnover markers, including alkaline phosphatase, N-telopeptides, and osteocalcin, were strongly correlated with TV and TA (P < 0.05) extracted from FD lesions in the entire skeleton. No associations were identified with SUVmax or SUVmean . Bone pain and age did not correlate with 18 F-NaF PET/CT parameters. FD burden evaluated by 18 F-NaF-PET/CT facilitates accurate assessment of FD activity, and correlates quantitatively with clinically-relevant skeletal outcomes. © 2019 American Society for Bone and Mineral Research.
| S-EPMC6744316 | biostudies-literature
Project description:The aim of this prospective investigation was to assess the association of 18F-FDG PET/CT with time to hormonal treatment failure (THTF) in men with metastatic castration-sensitive prostate cancer. Methods: 76 men with metastatic castration-sensitive prostate cancer recruited from 2005 to 2011 underwent 18F-FDG PET/CT and were followed prospectively for THTF, defined as treatment change to chemotherapy or death. Patients who had not switched to chemotherapy were censored at the last follow-up date (median of 36 mo; range, 12-108 mo). Cox regression analyses were performed to examine the association between PET/CT measurements: sum of SUVmax, maximum SUVmax, and average SUVmax for up to 10 of the most active lesions and THTF. Survival probabilities were based on the Kaplan-Meier method. Results: 43 patients had hormonal treatment failure, and 8 died without documented treatment failure. Median THTF was 26.5 mo (95% confidence interval [CI], 15.5-46.6 mo). The THTF-free probability at 5 y was 35% ± 6%. On univariate analysis, all PET parameters, including number of lesions, were statistically significant for THTF. In a reduced multivariate model accounting for clinical variables, only sum of SUVmax (hazard ratio, 1.01; 95% CI, 1.002-1.03; P = 0.024) and number of lesions (hazard ratio, 1.18; 95% CI, 1.08-1.29; P < 0.001) were independently associated with THTF. When sum of SUVmax was grouped into quartile ranges, there was a significantly worse survival probability for patients in the fourth-quartile range than in the first, with a univariate hazard ratio of 6.2 (95% CI, 2.8-13.6; P < 0.001). Conclusion: Sum of SUVmax and number of lesions derived from 18F-FDG PET/CT provide independent prognostic information on THTF in men with metastatic castration-sensitive prostate cancer.
| S-EPMC6836859 | biostudies-literature
Project description:BackgroundCardiac PET has recently found novel applications in coronary atherosclerosis imaging using [18F]NaF as a radiotracer, highlighting vulnerable plaques. However, the resulting uptakes are relatively small, and cardiac motion and respiration-induced movement of the heart can impair the reconstructed images due to motion blurring and attenuation correction mismatches. This study aimed to apply an MR-based motion compensation framework to [18F]NaF data yielding high-resolution motion-compensated PET and MR images.MethodsFree-breathing 3-dimensional Dixon MR data were acquired, retrospectively binned into multiple respiratory and cardiac motion states, and split into fat and water fraction using a model-based reconstruction framework. From the dynamic MR reconstructions, both a non-rigid cardiorespiratory motion model and a motion-resolved attenuation map were generated and applied to the PET data to improve image quality. The approach was tested in 10 patients and focal tracer hotspots were evaluated concerning their target-to-background ratio, contrast-to-background ratio, and their diameter.ResultsMR-based motion models were successfully applied to compensate for physiological motion in both PET and MR. Target-to-background ratios of identified plaques improved by 7 ± 7%, contrast-to-background ratios by 26 ± 38%, and the plaque diameter decreased by -22 ± 18%. MR-based dynamic attenuation correction strongly reduced attenuation correction artefacts and was not affected by stent-related signal voids in the underlying MR reconstructions.ConclusionsThe MR-based motion correction framework presented here can improve the target-to-background, contrast-to-background, and width of focal tracer hotspots in the coronary system. The dynamic attenuation correction could effectively mitigate the risk of attenuation correction artefacts in the coronaries at the lung-soft tissue boundary. In combination, this could enable a more reproducible and reliable plaque localisation.
| S-EPMC8241750 | biostudies-literature
Project description:Rationale: 225Ac, a long-lived α-emitter with a half-life of 9.92 days, has garnered significant attention as a therapeutic radionuclide when coupled with monoclonal antibodies and other targeting vectors. Nevertheless, its clinical utility has been hampered by potential off-target toxicity, a lack of optimized chelators for 225Ac, and limitations in radiolabeling methods. In a prior study evaluating the effectiveness of CD46-targeted radioimmunotherapy, we found great therapeutic efficacy but also significant toxicity at higher doses. To address these challenges, we have developed a radioimmunoconjugate called 225Ac-Macropa-PEG4-YS5, incorporating a stable PEGylated linker to maximize tumoral uptake and increase tumor-to-background ratios. Our research demonstrates that this conjugate exhibits greater anti-tumor efficacy while minimizing toxicity in prostate cancer 22Rv1 tumors. Methods: We synthesized Macropa.NCS and Macropa-PEG4/8-TFP esters and prepared Macropa-PEG0/4/8-YS5 (with nearly ~1:1 ratio of macropa chelator to antibody YS5) as well as DOTA-YS5 conjugates. These conjugates were then radiolabeled with 225Ac in a 2 M NH4OAc solution at 30 °C, followed by purification using YM30K centrifugal purification. Subsequently, we conducted biodistribution studies and evaluated antitumor activity in nude mice (nu/nu) bearing prostate 22Rv1 xenografts in both single-dose and fractionated dosing studies. Micro-PET imaging studies were performed with 134Ce-Macropa-PEG0/4/8-YS5 in 22Rv1 xenografts for 7 days. Toxicity studies were also performed in healthy athymic nude mice. Results: As expected, we achieved a >95% radiochemical yield when labeling Macropa-PEG0/4/8-YS5 with 225Ac, regardless of the chelator ratios (ranging from 1 to 7.76 per YS5 antibody). The isolated yield exceeded 60% after purification. Such high conversions were not observed with the DOTA-YS5 conjugate, even at a higher ratio of 8.5 chelators per antibody (RCY of 83%, an isolated yield of 40%). Biodistribution analysis at 7 days post-injection revealed higher tumor uptake for the 225Ac-Macropa-PEG4-YS5 (82.82 ± 38.27 %ID/g) compared to other conjugates, namely 225Ac-Macropa-PEG0/8-YS5 (38.2 ± 14.4/36.39 ± 12.4 %ID/g) and 225Ac-DOTA-YS5 (29.35 ± 7.76 %ID/g). The PET Imaging of 134Ce-Macropa-PEG0/4/8-YS5 conjugates resulted in a high tumor uptake, and tumor to background ratios. In terms of antitumor activity, 225Ac-Macropa-PEG4-YS5 exhibited a substantial response, leading to prolonged survival compared to 225Ac-DOTA-YS5, particularly when administered at 4.625 kBq doses, in single or fractionated dose regimens. Chronic toxicity studies observed mild to moderate renal toxicity at 4.625 and 9.25 kBq doses. Conclusions: Our study highlights the promise of 225Ac-Macropa-PEG4-YS5 for targeted alpha particle therapy. The 225Ac-Macropa-PEG4-YS5 conjugate demonstrates improved biodistribution, reduced off-target binding, and enhanced therapeutic efficacy, particularly at lower doses, compared to 225Ac-DOTA-YS5. Incorporating theranostic 134Ce PET imaging further enhances the versatility of macropa-PEG conjugates, offering a more effective and safer approach to cancer treatment. Overall, this methodology has a high potential for broader clinical applications.
| S-EPMC10879874 | biostudies-literature
Project description:Quantitative evaluation of radiolabeled prostate-specific membrane antigen (PSMA) PET scans may be used to monitor treatment response in patients with prostate cancer (PCa). To interpret longitudinal differences in PSMA uptake, the intrinsic variability of tracer uptake in PCa lesions needs to be defined. The aim of this study was to investigate the repeatability of quantitative PET/CT measurements using 18F-DCFPyL ([2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid], a second-generation 18F-PSMA-ligand) in patients with PCa. Methods: Twelve patients with metastatic PCa were prospectively included, of whom 2 were excluded from final analyses. Patients received 2 whole-body 18F-DCFPyL PET/CT scans (median dose, 317 MBq; uptake time, 120 min) within a median of 4 d (range, 1-11 d). After semiautomatic (isocontour-based) tumor delineation, the following lesion-based metrics were derived: mean, peak, and maximum tumor-to-blood ratio; SUVmean, SUVpeak, and SUVmax normalized to body weight; tumor volume; and total lesion uptake (TLU). Additionally, patient-based total tumor volume (TTV) (sum of PSMA-positive tumor volumes) and total tumor burden (TTB) (sum of all lesion TLUs) were derived. Repeatability was analyzed using repeatability coefficients (RC) and intraclass correlation coefficients. Additionally, the effect of point-spread function (PSF) image reconstruction on the repeatability of uptake metrics was evaluated. Results: In total, 36 18F-DCFPyL PET-positive lesions were analyzed (≤5 lesions per patient). The RCs for mean, peak, and maximum tumor-to-blood ratio were 31.8%, 31.7%, and 37.3%, respectively. For SUVmean, SUVpeak, and SUVmax, the RCs were 24.4%, 25.3%, and 31.0%, respectively. All intraclass correlation coefficients were at least 0.97. Tumor volume delineations were quite repeatable, with an RC of 28.1% for individual lesion volumes and 17.0% for TTV. TTB had an RC of 23.2% and 33.4% when based on SUVmean and mean tumor-to-blood ratio, respectively. Small lesions (<4.2 cm3) had worse repeatability for volume measurements. The repeatability of SUVpeak, TLU, and all patient-level metrics was not affected by PSF reconstruction. Conclusion: 18F-DCFPyL uptake measurements are quite repeatable and can be used for clinical validation in future treatment response assessment studies. Patient-based TTV may be preferred for multicenter studies because its repeatability was both high and robust to different image reconstructions.
| S-EPMC7456167 | biostudies-literature
Project description:PurposeRa-223 dichloride (223Ra, Xofigo®) is used for treatment of patients suffering from castration-resistant metastatic prostate cancer. The objective of this work was to apply the most recent biokinetic model for radium and its progeny to show their radiopharmacokinetic behaviour. Organ absorbed doses after intravenous injection of 223Ra were estimated and compared to clinical data and data of an earlier modelling study.MethodsThe most recent systemic biokinetic model of 223Ra and its progeny, developed by the International Commission on Radiological Protection (ICRP), as well as the ICRP human alimentary tract model were applied for the radiopharmacokinetic modelling of Xofigo® biodistribution in patients after bolus administration. Independent kinetics were assumed for the progeny of 223Ra. The time activity curves for 223Ra were modelled and the time integrated activity coefficients, [Formula: see text] in the source regions for each progeny were determined. For estimating the organ absorbed doses, the Specific Absorbed Fractions (SAF) and dosimetric framework of ICRP were used together with the aforementioned [Formula: see text] values.ResultsThe distribution of 223Ra after injection showed a rapid plasma clearance and a low urinary excretion. Main elimination was via faeces. Bone retention was found to be about 30% at 4 h post-injection. Similar tendencies were observed in clinical trials of other authors. The highest absorbed dose coefficients were found for bone endosteum, liver and red marrow, followed by kidneys and colon.ConclusionThe biokinetic modelling of 223Ra and its progeny may help to predict their distributions in patients after administration of Xofigo®. The organ dose coefficients of this work showed some variation to the values reported from clinical studies and an earlier compartmental modelling study. The dose to the bone endosteum was found to be lower by a factor of ca. 3 than previously estimated.
| S-EPMC8172819 | biostudies-literature
Project description:Background MRI and fluorine 18-labeled sodium fluoride (18F-NaF) PET can be used to identify features of plaque instability, rupture, and disease activity, but large studies have not been performed. Purpose To evaluate the association between 18F-NaF activity and culprit carotid plaque in acute neurovascular syndrome. Materials and Methods In this prospective observational cohort study (October 2017 to January 2020), participants underwent 18F-NaF PET/MRI. An experienced clinician determined the culprit carotid artery based on symptoms and record review. 18F-NaF uptake was quantified using standardized uptake values and tissue-to-background ratios. Statistical significance was assessed with the Welch, χ2, Wilcoxon, or Fisher test. Multivariable models were used to evaluate the relationship between the imaging markers and the culprit versus nonculprit vessel. Results A total of 110 participants were evaluated (mean age, 68 years ± 10 [SD]; 70 men and 40 women). Of the 110, 34 (32%) had prior cerebrovascular disease, and 26 (24%) presented with amaurosis fugax, 54 (49%) with transient ischemic attack, and 30 (27%) with stroke. Compared with nonculprit carotids, culprit carotids had greater stenoses (≥50% stenosis: 30% vs 15% [P = .02]; ≥70% stenosis: 25% vs 4.5% [P < .001]) and had increased prevalence of MRI-derived adverse plaque features, including intraplaque hemorrhage (42% vs 23%; P = .004), necrotic core (36% vs 18%; P = .004), thrombus (7.3% vs 0%; P = .01), ulceration (18% vs 3.6%; P = .001), and higher 18F-NaF uptake (maximum tissue-to-background ratio, 1.38 [IQR, 1.12-1.82] vs 1.26 [IQR, 0.99-1.66], respectively; P = .04). Higher 18F-NaF uptake was positively associated with necrosis, intraplaque hemorrhage, ulceration, and calcification and inversely associated with fibrosis (P = .04 to P < .001). In multivariable analysis, carotid stenosis at or over 70% (odds ratio, 5.72 [95% CI: 2.2, 18]) and MRI-derived adverse plaque characteristics (odds ratio, 2.16 [95% CI: 1.2, 3.9]) were both associated with the culprit versus nonculprit carotid vessel. Conclusion Fluorine 18-labeled sodium fluoride PET/MRI characteristics were associated with the culprit carotid vessel in study participants with acute neurovascular syndrome. Clinical trial registration no. NCT03215550 and NCT03215563 © RSNA, 2022 Online supplemental material is available for this article.
| S-EPMC9523682 | biostudies-literature
Project description:BackgroundThe standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant Ki expected from 18F-Sodium Fluoride (18F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for 18F-NaF and 18F-Fluorodeoxyglucose (18F-FDG) PET/MR cardiovascular imaging.MethodsWe introduce 5-class Ki/MR-AC for (i) 18F-NaF studies where the bones are segmented from Patlak Ki images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class Ki/MR-AC for (ii) 18F-FDG-only data, with a streamlined simultaneous administration of 18F-FDG and 18F-NaF at 4:1 ratio (R4:1), or (iii) for 18F-FDG-only or both 18F-FDG and 18F-NaF dual-tracer data, by administering 18F-NaF 90 minutes after an equal 18F-FDG dosage (R1:1). The Ki-driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD).ResultsIn rabbits, we observed similar (< 1.2% mean difference) vertebral bone 18F-NaF SUVmean scores when applying 5-class AC with Ki-segmented bone (5-class Ki/CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUVmean bias was reduced by 17.6% (18F-NaF) and 15.4% (R4:1) with 5-class Ki/CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher 18F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean 18F-FDG:18F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% (18F-FDG) and 15.5% (18F-NaF) at carotid bifurcations and 21.6% (18F-FDG) and 22.5% (18F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication.ConclusionsKi-driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance 18F-NaF and 18F-FDG contrast and quantification in bone tissues and carotid walls.
| S-EPMC7190435 | biostudies-literature