Assessment of Cu-ETS as a PET radiopharmaceutical for evaluation of regional renal perfusion

Species dependence of [64Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins

“…These radiopharmaceutical interactions with serum albumin are reversible, with radioTLC showing no evidence for chemical decomposition of the chelates, consistent with earlier findings [25,37]. Nevertheless, such albumin binding can be detrimental to drug delivery, particularly in applications requiring high first-pass tissue extraction of the pharmaceutical from blood, as is the case with radiotracer methods for probing regional tissue perfusion.…”

“…In this regard, the dramatically lower, and largely species-independent, binding of Cu-ETS to serum albumin [37] is expected to make Cu-ETS a more robust agent for evaluation of perfusion regardless of species. Cu-ETS remains under investigation as a tracer of myocardial and renal perfusion [22][23][24][25].…”

“…Like Cu-PTSM and Cu-ETS, the structurally related Cu-ATSM chelate can be reductively decomposed to intracellularly liberate (and trap) the copper radiolabel [25,33,[40][41][42][43]. However, for Cu-ATSM this redox trapping is sensitive to the level of cell oxygenation, occurring most rapidly in hypoxic cells, leading to investigation of [ 60,64 Cu[Cu-ATSM as a marker of tissue hypoxia [26][27][28][29][30][31].…”

“…1), have shown promise as PET radiopharmaceuticals for imaging tissue perfusion (Cu-PTSM, Cu-ETS) [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] and hypoxia (Cu-ATSM) [26][27][28][29][30][31][32]. The clinical utility of Cu-PTSM for quantifying perfusion in high-flow tissues, such as hyperemic myocardium, appears limited by the high affinity of this chelate for HSA, a result not predicted by the promising results from canine models [13].…”

Assessment of tissue perfusion by contrast-enhanced ultrasound

“…Laser Doppler [1], single photon computed tomography (SPECT) [2], multidetector computed tomography (CT) [3], magnetic resonance (MR) imaging [4] and positron emission tomography (PET) [5] all quantify tissue perfusion accurately but they are expensive and present some inherent limitations such as limited availability and patient exposure to radiation or nuclear tracers. Colour and power Doppler are limited by the low sensitivity to low-velocity flow in smaller vessels (<2 mm in diameter).…”