Safety, Dosimetry, and Tumor Detection Ability of <sup>68</sup>Ga-NOTA-AE105: First-in-Human Study of a Novel Radioligand for uPAR PET Imaging

Skovgaard, Dorthe; Persson, Morten; Brandt-Larsen, Malene; Christensen, Camilla L.; Madsen, Jacob; Klausen, Thomas Levin; Holm, Søren; Andersen, Flemming; Loft, Annika; Berthelsen, Anne Kiil; Pappot, Helle; Brasso, Klaus; Kroman, Niels; Højgaard, Liselotte; Kjær, Andreas

doi:10.2967/jnumed.116.178970

Cited by 64 publications

(67 citation statements)

References 31 publications

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“…Interestingly, suPAR has previously been shown to carry prognostic value in cancer patients 27,51 and may as such add to both diagnosing and prognosticating cancer patients and accordingly uPAR is currently pursued as a promising imaging and radiotherapeutic target. [52][53][54][55] In any case, the positive and negative predictive values must be examined in a larger patient cohort to establish a clinical cutoff, and combining high sensitivity biomarkers with high specificity biomarkers to detect cancer 6 or constructing a predictive model consisting of biomarkers and clinical information would also require development and validation in cohorts larger than the present.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Rasmussen

Schultz

Gaardsting

et al. 2017

Intl Journal of Cancer

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In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin‐3, mannose‐binding lectin, ficolin‐1, ficolin‐2 and ficolin‐3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were registered on admission, and plasma concentrations of biomarkers were measured. The primary outcome was incident cancer within 1 year. Out of 197 patients included, 39 patients (19.8%) were diagnosed with cancer. Patients with cancer were significantly older and had a higher burden of comorbidities and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C‐reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow‐up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs investigated nor self‐reported weight loss was associated with cancer. In this study, previous cancer, CRP and suPAR were significantly associated with cancer diagnosis in patients with NSSC. Ficolin‐1‐3, MBL and pentraxin‐3 were not associated with cancer.

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Section: Discussionmentioning

confidence: 99%

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Rasmussen

Schultz

Gaardsting

et al. 2017

Intl Journal of Cancer

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“…Furthermore, our group recently demonstrated that a uPAR bound ligand, 68Ga-NOTA-AE105, is safe and detects tumour tissue in men and women with cancer undergoing PET-CT. In the phase I clinical trial, six patients with PCa were included and the primary tumour lesions and metastases showed significant uptake of 68Ga-NOTA-AE105 37. This may hold a strong future for PET-CT for detection of lymph node metastasis in PCa.…”

Section: Discussionmentioning

confidence: 99%

Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

et al. 2017

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“…Therefore, the primary objective of this study was to determine suitable biomarkers for targeted molecular imaging in myxofibrosarcoma using immunohistochemical analyses of surgically obtained tumor specimens. Ten biomarker candidates were selected based on the literature and availability of imaging agents that specifically target these biomarkers [21][22][23][24][25][26][27][28][29] . The biomarker with the highest expression rate was subsequently evaluated on a selection of whole slides to evaluate the contrast between tumor tissue and adjacent benign regions.…”

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Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Gooyer

Versleijen-Jonkers²,

Hillebrandt-Roeffen³

et al. 2020

Sci Rep

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Myxofibrosarcoma(MFS) is the most common soft tissue sarcoma(STS) in elderly patients. Surgical resection remains the main treatment modality but tumor borders can be difficult to delineate with conventional clinical methods. Incomplete resections are a common problem and local recurrence remains a clinical issue. A technique that has shown great potential in improving surgical treatment of solid tumors is tumor targeted imaging and image-guided surgery with near-infrared fluorescence. To facilitate this technique, it is essential to identify a biomarker that is highly and homogenously expressed on tumor cells, while being absent on healthy non-malignant tissue. The purpose of this study was to identify suitable molecular targets for tumor-targeted imaging of myxofibrosarcoma. Ten potential molecular targets for tumor targeted imaging were investigated with immunohistochemical analysis in myxofibrosarcoma tissue (n = 34). Results were quantified according to the immunoreactive score(IRS). Moderate expression rates were found for uPAR, PDGFRa and EMA/MUC1. High expression rates of VEGF and TEM1 were seen. Strong expression was most common for TEM1 (88.2%). These results confirms that TEM1 is a suitable target for tumor-targeted imaging of myxofibrosarcoma. Keywords Image-guided surgery; Immunohistochemistry; Molecular imaging; Myxofibrosarcoma; Soft tissue sarcoma; Tumor endothelial marker 1(TEM1), Vascular endothelial growth factor (VEGF).Myxofibrosarcoma (MFS) is a histological subtype of soft tissue sarcoma (STS) formerly classified as a myxoidtype malignant fibrous histiocytoma. It has been reclassified and defined as a distinct pathological entity in the World Health Organization (WHO) criteria set in 2002 1,2 . Myxofibrosarcoma is a relatively common sarcoma in the elderly that mainly arises in the extremities 3 . Primary MFS most often presents as a subcutaneous painless, slow growing nodule, but completely infiltrative growth patterns along fascial planes without formation of an evident tumor mass have also been described 4 . The low-grade lesions have a relatively low metastatic potential but show a significant propensity for local recurrences 5-8 . These recurrences show higher-grade histology in up to 50% of all cases compared to the primary tumor 3 . Subsequently, high and intermediate grade disease exhibits a greater metastatic potential, mainly metastasizing to the lungs and lymph nodes 7,9 . Current guidelines recommend wide surgical resection combined with pre or post-operative radiotherapy as the preferred treatment 10 . Despite this strategy, positive margins after surgery occur in up to 20% of cases and reported local relapse rates range from 15 to 65% [5][6][7][8]11 .Currently clinicians rely on conventional imaging modalities such as CT and MRI to determine the location and extent of tumor burden prior to surgery. Translating these conventional imaging modalities to the surgical theatre remains challenging, forcing the surgeon to depend mainly on tactile and visual cues during the procedure. P...

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Safety, Dosimetry, and Tumor Detection Ability of ⁶⁸Ga-NOTA-AE105: First-in-Human Study of a Novel Radioligand for uPAR PET Imaging

Cited by 64 publications

References 31 publications

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

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Safety, Dosimetry, and Tumor Detection Ability of 68Ga-NOTA-AE105: First-in-Human Study of a Novel Radioligand for uPAR PET Imaging

Cited by 64 publications

References 31 publications

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

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Safety, Dosimetry, and Tumor Detection Ability of ⁶⁸Ga-NOTA-AE105: First-in-Human Study of a Novel Radioligand for uPAR PET Imaging