Selection of the first 99m^{99m} Tc-Labelled somatostatin receptor subtype 2 antagonist for clinical translation : preclinical assessment of two optimized candidates

Recently, radiolabelled antagonists targeting somatostatin receptors subtype 2 (SST2) in neuroendocrine neoplasms demonstrated certain superior properties over agonists. Within the ERA-PerMED project “TECANT” two 99mTc-Tetramine (N4)-derivatized SST2 antagonists (TECANT-1 and TECANT-2) were studied for the selection of the best candidate for clinical translation. Receptor-affinity, internalization and dissociation studies were performed in human embryonic kidney-293 (HEK293) cells transfected with the human SST2 (HEK-SST2). Log D, protein binding and stability in human serum were assessed. Biodistribution and SPECT/CT studies were carried out in nude mice bearing HEK-SST2 xenografts, together with dosimetric estimations from mouse-to-man. [99mTc]Tc-TECANT-1 showed higher hydrophilicity and lower protein binding than [99mTc]-TECANT-2, while stability was comparable. Both radiotracers revealed similar binding affinity, while [99mTc]Tc-TECANT-1 had higher cellular uptake (>50%, at 2 h/37 °C) and lower dissociation rate (<30%, at 2 h/37 °C). In vivo, [99mTc]Tc-TECANT-1 showed lower blood values, kidney and muscles uptake, whereas tumour uptake was comparable to [99mTc]Tc-TECANT-2. SPECT/CT imaging confirmed the biodistribution results, providing the best tumour-to-background image contrast for [99mTc]Tc-TECANT-1 at 4 h post-injection (p.i.). The estimated radiation dose amounted to approximately 6 µSv/MBq for both radiotracers. This preclinical study provided the basis of selection of [99mTc]Tc-TECANT-1 for clinical translation of the first 99mTc-based SST2 antagonist

Imaging microvascular changes in nonocular oncological clinical applications by optical coherence tomography angiography: a literature review

Optical coherence tomography angiography (OCTA) is an emerging imaging modality that enables noninvasive visualization and analysis of tumor vasculature. OCTA has been particularly useful in clinical ocular oncology, while in this article, we evaluated OCTA in assessing microvascular changes in clinical nonocular oncology through a systematic review of the literature

Optimal scan time for evaluation of parathyroid adenoma with [18F]-fluorocholine PET/CT

Background. Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign tumours which autonomously produce and secrete parathyroid hormone. [18F]-fluorocholine (FCH), PET marker of cellular proliferation, was recently demonstrated to accumulate in lesions representing enlarged parathyroid tissue; however, the optimal time to perform FCH PET/CT after FCH administration is not known. The aim of this study was to determine the optimal scan time of FCH PET/CT in patients with primary hyperparathyroidism

Cumulative input function method for linear compartmental models and spectral analysis in PET

Compartmental modeling and spectral analysis are often used for tracer kinetic modeling in positron emission tomography (PET). The concentrations in kinetic equations are usually considered to be instantaneous, whereas PET data are inherently integrated over time, which leads to uncertainties in the results. A new formalism for kinetic analysis that uses cumulative tracer concentrations and avoids approximating the image-derived input function and PET measurements with midframe instantanous values was developed. We assessed the improvements of the new formalism over the midframe approximation methods for three commonly used radiopharmaceuticals: [11C]raclopride, 2′-deoxy-2′-[18F]fluoro--glucose (FDG), and 3′-deoxy-3′-[18F]fluoro-thymidine (FLT). We found that improvements are case dependent and often not negligible. Improvements for determination of binding potential for [11C]raclopride ranged from 5% to 25%. Improvements in estimation accuracy of FDG and FLT microparameters ranged up to 25%. On the other hand, estimation of macroparameter Ki=K1k3/(k2+k3) for FDG or FLT did not show significant benefit with the new method; only modest improvement up to 2% was observed. Assessment of the benefits of using new method is far from being exhaustive, but possibly significant improvement was demonstrated. Therefore, we consider the proposed algorithm a necessary component of any kinetic analysis software