Dataset Information

Clinical Translation of an Albumin-Binding PET Radiotracer 68Ga-NEB.

ABSTRACT: UNLABELLED:Suitably labeled Evans blue dye has been successfully applied to evaluate cardiac function, vascular permeability, and lymphatic imaging in preclinical settings. This study documented the first-in-human application of 68Ga-1,4,7-triazacyclononane-N,N',N?-triacetic acid (NOTA)-NEB. METHODS:The NOTA-conjugated truncated form of Evans blue, NEB, was labeled with 68Ga and tested in BALB/C mice for dynamic PET and ex vivo biodistribution studies. Three healthy volunteers (2 men and 1 woman) underwent 90-min whole-body dynamic PET. The absorbed doses for major organs and whole body were calculated using OLINDA/EXM software. Eleven patients with focal hepatic lesions diagnosed by enhanced CT or MR imaging were subjected to whole-body PET/CT acquisitions at 30 min after intravenous injection of 111-148 MBq (3-4 mCi) of 68Ga-NEB. RESULTS:NEB dye was labeled with 68Ga (half-time, 68 min) with high yield and purity. After intravenous injection, 68Ga-NEB formed a complex with serum albumin, thus most of the radioactivity was retained in blood circulation. The tracer was demonstrated to be safe in both healthy volunteers and recruited patients without side effects or allergies. Among the 11 patients, hemangiomas showed much higher 68Ga-NEB signal intensity than the surrounding normal hepatic tissues, whereas no apparent difference between lesions and hepatic tissues was identified on 18F-FDG PET. All other focal hepatic lesions including hepatocellular carcinoma, hepatic cysts, and neuroendocrine tumor liver metastases showed negative 68Ga-NEB contrast to hepatic tissues. CONCLUSION:As a blood-pool imaging agent, 68Ga-NEB is safe to use in the clinic, and our preliminary studies demonstrate the value of differentiating hepatic hemangioma from other benign or malignant focal hepatic lesions. Easy labeling with different positron emitters of various half-lives, excellent pharmacokinetics, and imaging quality warrant further clinical applications of NEB-based PET tracers.

SUBMITTER: Zhang J

PROVIDER: S-EPMC5238512 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Clinical Translation of an Albumin-Binding PET Radiotracer 68Ga-NEB.

Zhang Jingjing J Lang Lixin L Zhu Zhaohui Z Li Fang F Niu Gang G Chen Xiaoyuan X

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20150806 10

<h4>Unlabelled</h4>Suitably labeled Evans blue dye has been successfully applied to evaluate cardiac function, vascular permeability, and lymphatic imaging in preclinical settings. This study documented the first-in-human application of 68Ga-1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA)-NEB.<h4>Methods</h4>The NOTA-conjugated truncated form of Evans blue, NEB, was labeled with 68Ga and tested in BALB/C mice for dynamic PET and ex vivo biodistribution studies. Three healthy volunteers (2 ...[more]

PMID: 26251416

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Project description:68Ga-NOTA-WL12 is a peptide-based PET imaging agent. We conducted a first-in-human study of 68Ga-NOTA-WL12 for PET to study the in vivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying programmed death ligand-1 (PD-L1) expression levels in patients with advanced non-small cell lung cancer (NSCLC). Methods: In vitro assessment of the PD-L1 expression and cellular uptake of 68Ga-NOTA-WL12 was performed, followed by in vivo evaluation of 68Ga-NOTA-WL12 uptake in mouse models with tumors. Nine patients with NSCLC with lesions expressing PD-L1 were enrolled and monitored for adverse events during the study. 68Ga-NOTA-WL12 and paired 18F-FDG PET/CT imaging were performed. Uptake (SUV, SUL [SUVlean], and kBq/mL) values of tumors and normal organs were obtained. Radiopharmaceutical biodistribution, radiation dosimetry, and the relationship of tumor uptake to PD-L1 expression were evaluated. Follow-up 18F-FDG PET/CT was performed in patients who had undergone treatment with a combination of pembrolizumab with chemotherapy. Results:68Ga-NOTA-WL12 exhibited PD-L1-specific uptake in vitro and in PD-L1-positive tumors in vivo. 68Ga-NOTA-WL12 PET imaging proved safe with acceptable radiation dosimetry. Physiologic tracer uptake was mainly visible in the liver, spleen, small intestine, and kidney. Tumors were clearly visible, particularly in the lungs, with a tumor-to-lung ratio of 4.45 ± 1.89 at 1 h. One hour was a suitable time point for image acquisition because no significant differences were noted in tumor-to-background ratios between 1 and 2 h. A strong, positive correlation was found between tumor uptake (SUVpeak) and PD-L1 immunohistochemistry results (r = 0.9349; P = 0.002). 68Ga-NOTA-WL12 and 18F-FDG PET studies suggest that PD-L1 PET before therapy may indicate the therapeutic efficacy of pembrolizumab plus chemotherapy combination treatment. Conclusion: Our first-in-human findings demonstrate the safety and feasibility of 68Ga-NOTA-WL12 for noninvasive, in vivo detection of tumor PD-L1 expression levels, indicating potential benefits for clinical PD-L1 therapy.

Project description:ImportanceIn retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging.ObjectiveTo assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial.Design, setting, and participantsIn this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard.Main outcomes and measuresEndpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety.ResultsA total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients.Conclusions and relevanceUsing blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer.Trial registrationClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.

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Dataset Information

Clinical Translation of an Albumin-Binding PET Radiotracer 68Ga-NEB.

Publications

Clinical Translation of an Albumin-Binding PET Radiotracer 68Ga-NEB.

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