Synthesis and Biologic Evaluation of ⁶⁴Cu-Labeled Rhenium-Cyclized α-MSH Peptide Analog Using a Cross-Bridged Cyclam Chelator

Comparison of biodistribution of ⁶⁴Cu-DOTA-ReCCMSH(Arg¹¹) (185 kBq [5 μCi], 16 ng, n = 4; □) (8) and ⁶⁴Cu-CBTE2A-ReCCMSH(Arg¹¹) (185 kBq [5 μCi], 16 ng, n = 5; ▴) in B16/F1 tumor-bearing C57 mice at 2 h after injection. Data are presented as %ID/g ± SD. Note differences in y-axis scales.

Biodistribution comparison of ⁶⁴Cu-CBTE2A-ReCCMSH(Arg¹¹) with high SA (2 ng) and low SA (16 ng) and effect of preinjection of 15 mg d-lysine (2 h after injection).

Selected tumor-to-organ ratios for ⁶⁴Cu-DOTA-ReCMSH(Arg¹¹) (8), ⁶⁴Cu-CBTE2A-ReCCMSH(Arg¹¹) with lower and higher SA, and ⁸⁶Y-DOTA-ReCCMSH(Arg¹¹) (8) at 2 h in C57 mice implanted with B16/F1 tumors. (P = ReCCMSH(Arg¹¹).)

(A) Coronal images of C57 mice implanted with B16/F1 tumors at 30 min and at 2, 4, and 24 h after tail vein injection of 5.55 MBq (150 μCi) (500 ng) of ⁶⁴Cu-CBTE2A-ReCCMSH(Arg¹¹). At each time point a mouse that received blockade (left) was coimaged with a mouse that did not receive blockade (right). Blockade mouse received 20 μg of CBTE2A-ReCCMSH(Arg¹¹). Images shown are 1-mm slices, with animal in supine position, and slices shown are through center of tumor volume. As tumors do not grow in exactly the same location from animal to animal, slices may show different tissues in addition to tumors. PET images show that administration of a blockade dose substantially reduces tumor uptake of the agent by such an extent that tumor is difficult to delineate. It is also evident that background accumulation is very low, resulting in excellent tumor contrast. T = tumor; K = kidney. (B) microPET/CT coregistered images of B16/F1 tumor-bearing mice 2 h after tail vein injection of 5.5 MBq (500 ng) of ⁶⁴Cu-CBTE2A-ReCCMSH(Arg¹¹). Images shown are 1-mm slices and slices shown are through center of tumor volume.