Summary: Recently, the CD44v6-targeted radiopharmaceutical [¹⁷⁷Lu]Lu-AKIR001 has demonstrated therapeutic efficacy across several malignancies. In this preclinical study, the effect of the combination of [¹⁷⁷Lu]Lu-AKIR001 with the chemotherapeutic agents gemcitabine or paclitaxel was compared against [¹⁷⁷Lu]Lu-AKIR001 monotherapy in pancreatic ductal adenocarcinoma models. To quantify treatment efficacy and safety, several evaluations were conducted: radiopharmaceutical stability assays, cell line characterization, biodistribution profiles, in vivo therapeutic efficacy, and toxicity assessments.

Results from nanoScan^® SPECT/CT: To determine the biodistribution of [¹⁷⁷Lu]Lu-AKIR001, mice (N = 12) were imaged at multiple time points (24, 96, and 168 h post-injection) using a Mediso nanoScan SPECT/CT scanner. Injected activities were 12 MBq for the monotherapy group and 4 MBq for the combination therapy groups. CT images were acquired using 480 projections (50 kVp, 610 µA, 1:4 binning) and reconstructed via filtered back-projection (FBP). Whole-body SPECT scans were performed over 15 min with a 10 s frame time, utilizing the energy windows of ¹⁷⁷Lu (208.4 keV, 112.9 keV, and 56.1 keV). Raw SPECT data were reconstructed using the Tera-Tomo 3D algorithm (12 iterations, 3 subsets) within Nucline software.

Fig. 1 Biodistribution of [¹⁷⁷Lu]Lu-AKIR001. (A) Mice (N =12) bearing BxPC3 tumors were injected with [¹⁷⁷Lu]Lu-AKIR001 and dissected at 24 (N = 4), 96 (N = 4), and 168 h (N = 4) post injection. Error bars represent SD. (B) Representative SPECT/CT images at 96 h postejection gastrointestinal.

 

Imaging results revealed that peak tumor uptake occurred at 96 hours post-injection. Overall, the study demonstrates that the co-administration of [¹⁷⁷Lu]Lu-AKIR001 with paclitaxel offers significant therapeutic potential.

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