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Quantitative assessment of ventilation-perfusion relationships with gallium-68 positron emission tomography/computed tomography imaging in lung cancer patients.

ABSTRACT: Pulmonary functional imaging has demonstrated potential to improve thoracic radiotherapy. The purpose of this study was twofold: 1) to quantify ventilation/perfusion relationships in lung cancer patients using a new functional imaging approach, gallium-68 (⁶⁸Ga)-positron emission tomography/computed tomography (PET/CT); and 2) to compare ventilation/perfusion matching with diffusing capacity of the lung for carbon monoxide (D_LCO). Voxel-wise correlations between ventilation and perfusion varied widely among 19 patients (range: 0.26-0.88). ⁶⁸Ga-PET/CT-measured percent gas exchanging lung volume was moderately correlated with D_LCO (≤0.59). Our findings suggested that ⁶⁸Ga-PET/CT ventilation/perfusion imaging provided complementary information and a reasonable surrogate for gas exchange in lung cancer patients.

SUBMITTER: Li Z

PROVIDER: S-EPMC9018442 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Quantitative assessment of ventilation-perfusion relationships with gallium-68 positron emission tomography/computed tomography imaging in lung cancer patients.

Li Zhuorui Z Le Roux Pierre-Yves PY Callahan Jason J Hardcastle Nicholas N Hofman Michael S MS Siva Shankar S Yamamoto Tokihiro T

Physics and imaging in radiation oncology 20220411

Pulmonary functional imaging has demonstrated potential to improve thoracic radiotherapy. The purpose of this study was twofold: 1) to quantify ventilation/perfusion relationships in lung cancer patients using a new functional imaging approach, gallium-68 (<sup>68</sup>Ga)-positron emission tomography/computed tomography (PET/CT); and 2) to compare ventilation/perfusion matching with diffusing capacity of the lung for carbon monoxide (D<sub>LCO</sub>). Voxel-wise correlations between ventilation ...[more]

PMID: 35465222

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Project description:ImportanceAdrenal vein sampling (AVS) is the recommended procedure for subtyping primary aldosteronism (PA) as unilateral PA (UPA) or bilateral PA (BPA), with different treatment needed for each: adrenalectomy for UPA and medication for BPA. However, AVS is invasive and technically difficult, and how to subtype PA noninvasively is currently a great challenge.ObjectiveTo evaluate the accuracy of gallium-68 pentixafor positron emission tomography-computed tomography (PET-CT) in subtyping PA using AVS as a reference standard.Design, setting, and participantsThis diagnostic study was conducted at a tertiary hospital in China among patients diagnosed with PA. Enrollment was started in November 2021, with follow-up ending in May 2022.Exposures: Patients were recruited to undergo gallium-68 pentixafor PET-CT and AVS.Main outcomes and measuresMaximum standardized uptake value (SUVmax) of each adrenal gland during PET-CT was measured to calculate the lateralization index of SUVmax. Area under the receiver operating characteristic curve (AUROC), specificity, and sensitivity were used to analyze the accuracy of the lateralization index based on SUVmax for subtyping PA.ResultsAmong 100 patients with PA who completed the study (47 female [47.0%] and 53 male [53.0%]; median [IQR] age, 49 [38-56] years), 43 individuals had UPA and 57 individuals had BPA. Aldosterone-cortisol ratio (Spearman ρ = 0.26; P < .001) in adrenal veins was positively correlated with SUVmax of adrenal glands at 10 minutes during PET-CT. Using lateralization index based on SUVmax at 10 minutes to identify UPA, the AUROC was 0.90 (95% CI, 0.83-0.97). A cutoff value for lateralization index based on SUVmax at 10 minutes set at 1.65 conferred a specificity of 1.00 (95% CI, 0.94-1.00) and sensitivity of 0.77 (95% CI, 0.61-0.88). The diagnostic concordance rate of PET-CT and AVS was 90 patients (90.0%) compared with 54 patients (54.0%) between traditional CT and AVS.Conclusions and relevanceThis study found good diagnostic accuracy of gallium-68 pentixafor PET-CT in differentiating UPA from BPA. These findings suggest that gallium-68 pentixafor PET-CT may be used to avoid invasive AVS in some patients with PA.

Project description:BackgroundEvaluating the efficacy of focal therapy for prostate cancer is limited by current approaches and may be improved with biological imaging techniques.ObjectiveWe assessed whether positron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) can be used to predict relapse after vascular-targeted photodynamic therapy (VTP).Design, setting, and participantsA total of 1×106 LNCaP cells were grafted subcutaneously in the flanks of 6-8-wk-old SCID mice. Of 24 mice with measurable tumors 6 wk after tumor implantation, 20 were treated with VTP (150mW/cm2) to ablate the tumors. Blood prostate-specific antigen (PSA) levels were assessed, and ⁶⁸Ga-PSMA PET/CT images were performed 1 d before VTP and 1 and 4 wk after.Outcome measurements and statistical analysisLocal tumor relapse was evaluated by histology, and tumors were analyzed by prostate-specific membrane antigen (PSMA) and PSA immunohistochemistry. T tests and Kruskal-Wallis tests were used to determine significance.Results and limitationsFour weeks after VTP, 11 (65%) mice had complete responses and six (35%) had tumor relapses confirmed by histology (hematoxylin and eosin, and PSMA immunohistochemistry). All mice with local relapse had positive 68Ga-PSMA PET/CT findings 4 wk after VTP; all complete responders did not. One week after VTP, the relapse detection sensitivity of 68Ga-PSMA PET/CT was 75%, whereas the sensitivity of PSA was only 33%. Compared with controls, relapsed tumors had a three-fold reduction in the number of cells with strong PSA staining by immunohistochemistry (1.5% vs 4.5%; p=0.01).ConclusionsIn a preclinical prostate cancer model, we show that 68Ga-PSMA PET/CT can identify and predict relapse earlier than blood PSA level. These findings support further testing in clinical trials.Patient summaryPositron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen may be used to follow and evaluate treatment outcomes in men who receive focal therapy for prostate cancer.

Project description:COPD and smoking are characterised by pulmonary inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker. To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in "usual" (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients. Data from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKi and systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKi values at baseline and at 4-month follow-up. COPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001 versus 0.0028±0.001 mL·cm-3·min-1, respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi (β=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory volume in 1 s % predicted, systemic neutrophils and C-reactive protein levels. Mean percentage difference in nKi between the baseline and follow-up was 3.2%, and the within subject coefficient of variability was 7.7%. FDG PET/CT has potential as a noninvasive tool to enable whole lung and regional quantification of FDG uptake to assess smoking- and COPD-related pulmonary inflammation.

Project description:The role of the multivalent effect has been well recognized in the design of molecular imaging probes toward the desired imaging signal amplification. Recently, we reported a bifunctional chelator (BFC) scaffold design, which provides a simple and versatile approach to impart multivalency to radiometal based nuclear imaging probes. In this work, we report a series of BFC scaffolds ((t)Bu(3)-1-COOH, (t)Bu(3)-2-(COOH)(2), and (t)Bu(3)-3-(COOH)(3)) constructed on the framework of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for (68)Ga-based PET probe design and signal amplification via the multivalent effect. For proof of principle, a known integrin ?(v)?(3) specific ligand (c(RGDyK)) was used to build the corresponding NOTA conjugates (H(3)1, H(3)2, and H(3)3), which present 1-3 copies of c(RGDyK) peptide, respectively, in a systematic manner. Using the integrin ?(v)?(3) binding affinities (IC(50) values), enhanced specific binding was observed for multivalent conjugates (H(3)2: 43.9 ± 16.1 nM; H(3)3: 14.7 ± 5.0 nM) as compared to their monovalent counterpart (H(3)1: 171 ± 60 nM) and the intact c(RGDyK) peptide (204 ± 76 nM). The obtained conjugates were efficiently labeled with (68)Ga(3+) within 30 min at room temperature in high radiochemical yields (>95%). The in vivo evaluation of the labeled conjugates, (68)Ga-1, (68)Ga-2, and (68)Ga-3, was performed using male severe combined immunodeficiency (SCID) mice bearing integrin ?(v)?(3) positive PC-3 tumor xenografts (n = 3). All (68)Ga-labeled conjugates showed high in vivo stability with no detectable metabolites found by radio-HPLC within 2 h postinjection (p.i.). The PET signal amplification in PC-3 tumor by the multivalent effect was clearly displayed by the tumor uptake of the (68)Ga-labeled conjugates ((68)Ga-3: 2.55 ± 0.50%ID/g; (68)Ga-2: 1.90 ± 0.10%ID/g; (68)Ga-1: 1.66 ± 0.15%ID/g) at 2 h p.i. In summary, we have designed and synthesized a series of NOTA-based BFC scaffolds with signal amplification properties, which may find potential applications as diagnostic gallium radiopharmaceuticals.

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Dataset Information

Quantitative assessment of ventilation-perfusion relationships with gallium-68 positron emission tomography/computed tomography imaging in lung cancer patients.

Publications

Quantitative assessment of ventilation-perfusion relationships with gallium-68 positron emission tomography/computed tomography imaging in lung cancer patients.

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