Gallium-68-labeled DOTA-rhenium-cyclized alpha-melanocyte-stimulating hormone analog for imaging of malignant melanoma

Abstract

Introduction: Diagnosis of malignant melanoma is critical, since a patient's prognosis is poor. Previous studies have shown that 64Cu- and 86Y-DOTA-ReCCMSH(Arg11) have the potential for early detection of malignant melanoma by exploiting the sensitivity and high resolution of positron emission tomography (PET). This encouraged us to investigate DOTA-ReCCMSH(Arg11) labeled with another beta+-emitting radionuclide, 68Ga.

Methods: DOTA-ReCCMSH(Arg11) was successfully labeled with 68Ga at pH 3.8-4 at 85 degrees C. Acute biodistribution and small-animal PET imaging studies were performed in mice bearing B16/F1 melanoma tumor.

Results: Biodistribution studies showed moderate receptor-mediated tumor uptake, fast nontarget organ clearance and high tumor to nontarget tissue ratios. Preadministration of d-lysine significantly reduced kidney uptake without affecting the uptake of the agent in the tumor. Small-animal PET images showed that the tumor could be clearly visualized at all time points examined (0.5-2 h) with the standardized uptake value analysis following a similar trend as the biodistribution data.

Conclusions: The preliminary data obtained suggest that 68Ga-DOTA-ReCCMSH(Arg11) is a promising PET imaging agent for early detection of malignant melanoma.

Fig. 1

Selected tumor/organ ratios for ⁶⁴Cu-DOTA-ReCMSH(Arg¹¹) [40], ⁶⁸Ga-DOTA-ReCCMSH(Arg¹¹) and ⁶⁴Cu-CBTE2A-ReCCMSH(Arg¹¹) [46] at 2 h in C57BL/6 mice implanted with B16/F1 tumors. (P = ReCCMSH(Arg¹¹))

Fig. 2

Transverse (A), coronal (B) and sagittal images (C) images of C57BL/6 mice implanted with B16/F1 tumors at 2 h after tail vein injection of 100 μCi (2 μg) of ⁶⁸Ga-DOTA-ReCCMSH(Arg¹¹). A mouse that received blockade (left) was co-imaged with a mouse that did not receive blockade (right). Blockade mouse received 20 μg of unlabeled peptide. The mice were anesthetized with 1 – 2% isoflurane, positioned supine, immobilized and imaged. Ten minute static data sets were collected at each time point. The images shown are 1 mm slices, with the animal in the supine position, and the slices shown are through the center of the tumor volume. The PET images show that the administration of a blockade dose substantially reduces tumor uptake of the agent by such an extent that the tumor is difficult to delineate. (T = tumor, K = kidney, B = bladder)

Fig. 3

SUV data obtained for PET analysis of ⁶⁸Ga-DOTA-ReCCMSH(Arg¹¹) in C57BL/6 mice implanted with B16/F1 tumors.