Data_Sheet_1_In vivo behavior of [64Cu]NOTA-terpyridine platinum, a novel chemo-radio-theranostic agent for imaging, and therapy of colorectal cancer.docx

To overcome resistance to chemotherapy for colorectal cancer, we propose to validate in vivo a novel terpyridine-platinum (TP) compound radiolabeled with the radio-theranostic isotope 64Cu. In vivo stability, biodistribution, PET imaging, tumor growth delay, toxicity and dosimetry of [64Cu]NOTA-C3-TP were determined. The current experimental studies show that [64Cu]NOTA-C3-TP is stable in vivo, rapidly eliminated by the kidneys and has a promising tumor uptake ranging from 1.8 ± 0.4 to 3.0 ± 0.2 %ID/g over 48 h. [64Cu]NOTA-C3-TP retarded tumor growth by up to 6 ± 2.0 days and improved survival relative to vehicle and non-radioactive [NatCu]NOTA-C3-TP over 17 days of tumor growth observation. This effect was obtained with only 0.4 nmol i.v. injection of [64Cu]NOTA-C3-TP, which delivers 3.4 ± 0.3 Gy tumoral absorbed dose. No evidence of toxicity, by weight loss or mortality was revealed. These findings confirm the high potential of [64Cu]NOTA-TP as a novel radio-theranostic agent.</p

Development of Bifunctional Chelates Bearing Hydroxamate Arms for Highly Efficient ⁶⁴Cu Radiolabeling

Convenient approaches for the synthesis of DOTHA₂ and NOTHA₂, two cyclic bifunctional chelates (BFCs) bearing hydroxamate arms, have been developed. These novel BFCs coordinate ⁶⁴Cu with fast kinetics at room temperature in a wide range of concentrations and pH. The corresponding radiochemical complexes showed high stability, low residual activity in various tissues, and fast clearance in normal mice. The ability to conjugate DOTHA₂ to both a small peptide and a large protein is also reported

Synthesis and Evaluation of a ⁶⁴Cu-Conjugate, a Selective δ‑Opioid Receptor Positron Emission Tomography Imaging Agent

Given the putative selectivity of the antagonist TIPP (Tyr-Tic-Phe-Phe) for δ-opioid receptors (DOP), this compound was selected for the design of a novel ⁶⁴Cu-radiolabeled potent and selective DOP positron emission tomography (PET) imaging agent. <i>Ex vivo</i> autoradiography of TIPPD-PEG-K­(NOTA/⁶⁴Cu)-NH₂ on rat brain sections produced a distribution pattern consistent with the known expression of DOP. Taken together, the <i>in vitro</i> and <i>ex vivo</i> data indicate that this ⁶⁴Cu-tracer holds promise for studying the DOP by means of PET