Evaluation of integrin αvβ6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin αvβ6

Initial experience with a SiPM-based PET/CT scanner: influence of acquisition time on image quality

Abstract Background A newly introduced PET/CT scanner (Discovery Meaningful Insights—DMI, GE Healthcare) includes the silicon photomultiplier (SiPM) with time-of-flight (TOF) technology first used in the GE SIGNA PET/MRI. In this study, we investigated the impact of various acquisition times on image quality using this SiPM-based PET/CT. Methods We reviewed data from 58 participants with cancer who were scanned using the DMI PET/CT scanner. The administered dosages ranged 295.3–429.9 MBq (mean ± SD 356.3 ± 37.4) and imaging started at 71–142 min (mean ± SD 101.41 ± 17.52) after administration of the radiopharmaceutical. The patients’ BMI ranged 19.79–46.16 (mean ± SD 26.55 ± 5.53). We retrospectively reconstructed the raw TOF data at 30, 60, 90, and 120 s/bed and at the standard image acquisition time per clinical protocol (180 or 210 s/bed depending on BMI). Each reconstruction was reviewed blindly by two nuclear medicine physicians and scored 1–5 (1—poor, 5—excellent quality). The liver signal-to-noise ratio (SNR) was used as a quantitative measure of image quality. Results The average scores ± SD of the readers were 2.61 ± 0.83, 3.70 ± 0.92, 4.36 ± 0.82, 4.82 ± 0.39, and 4.91 ± 0.91 for the 30, 60, 90, and 120 s/bed and at standard acquisition time, respectively. Inter-reader agreement on image quality assessment was good, with a weighted kappa of 0.80 (95% CI 0.72–0.81). In the evaluation of the effects of time per bed acquisition on semi-quantitative measurements, we found that the only time point significantly different from the standard time were 30 and 60 s (both with P  25, images can be acquired as fast as 90 s/bed using the SiPM PET/CT and still result in very good image quality (average score > 4)

18F-florbetaben whole-body PET/MRI for evaluation of systemic amyloid deposition

Abstract Background Florbetaben, a 18F-labeled stilbene derivative (Neuraceq®, formerly known as BAY-949172), is a diagnostic radiopharmaceutical developed to visualize β-amyloid plaques in the brain. Here, we report a pilot study evaluating patients with suspected cardiac amyloidosis for systemic extent of disease. Methods We prospectively enrolled nine patients, 61–86 year old (mean ± SD 69.4 ± 8.6), referred from the cardiac amyloid clinic. First, dynamic imaging of the heart was acquired immediately after injection of 222–318.2 MBq (mean ± SD 270.1 ± 33.3) of 18F-florbetaben using the GE SIGNA PET/MRI. This was followed by a whole-body PET/MRI scan 60–146.4 min (mean ± SD 98 ± 33.4) after injection. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Whole-body MRI sequences included MRAC and axial T1-weighted imaging. Results High early uptake and delayed high uptake in the left ventricle correlated with amyloid deposition in five patients, while low uptake on early and delayed cardiac imaging was noted in four patients. Cardiac function measurements were successfully obtained in all participants. Areas of increased abnormal 18F-florbetaben accumulation were noted on delayed whole-body imaging in the bone marrow (seven patients), stomach (diffuse in five patients and focal in one patient), brain (five patients), salivary glands (three patients), tongue (three patients), spleen (three patients), skeletal muscles (three patients), ocular muscles (two patients), thyroid (two patients), pleura (two patients), kidneys (two patients), and lungs (two patients). Conclusions Whole-body 18F-florbetaben PET/MRI is promising for localization of systemic amyloid deposition. This technique may provide important structural and functional information regarding the organs involved by disease, with potential to guide biopsy and evaluate response to treatment. Trial registration Clinicaltrials.gov registration: NCT03119558

D600 PET/CT vs DMI PET/CT: no additional bone lesions were detected by DMI PET/CT compared to standard PET/CT.

<p>61 years-old man with tonsillar cancer who underwent PET/CT for evaluation of response to therapy. DMI images were acquired 47.4 minutes after standard acquisition and 126 minutes after ¹⁸F-FDG injection. A) D600 MIP; B) DMI MIP; C) D600 sagittal fused image; D) DMI sagittal fused image.</p

D690 PET/CT vs DMI PET/CT at different time delay between scans.

<p>A1) D690 PET; A2) D690 CT; A3) D690 fused image; B1) DMI PET; B2) DMI CT; B3) DMI fused image. Time delay between scans was 18 minutes. C1) D690 PET; C2) D690 CT; C3) D690 fused image; D1) DMI PET; D2) DMI CT; D3) DMI fused image. Time delay between scans was 73.7 minutes.</p

Equivalence testing of baseline organs matched per patient per PET/CT scan type.

<p>Equivalence testing of baseline organs matched per patient per PET/CT scan type.</p