Canine PET/CT imaging with 64Cu-nanomedicines

Introduction: Men diagnosed with metastatic prostate cancer are faced with a poor prognosis due to the low specificity of currently available treatment options. Conventional chemotherapy, whilst efficaciously able to target multiple sites of disease, is administered systemically and leads to dose-limiting toxicity in normal healthy cells.^[1] Studies in mice with the use of polyethylene glycol [PEG] based hyper-branched polymers [HBP] as a carrier vehicle for doxorubicin have shown significant promise in a new targeted drug delivery approach, delivering a payload of chemotherapy directly to the prostate cancer cells.^[1,2] However, transgenic mice models may be a poor predictor of the human experience owing to the differing metabolic pathways and non-spontaneous nature of tumour cells, obviating the need to assess these materials in translational large animal models.^[3] The utility of comparative oncology and PET/CT offers the opportunity to study the pathways of novel drug delivery and target specific receptors in spontaneously occurring prostate cancers, leading to a new generation of “personalised medicine”.

Methods: All PET/CT examinations were performed on a SIEMENS Biograph Horizon PET/CT scanner. General anaesthesia was used for all imaging procedures, and heart rate, blood pressure, and SpO2 were carefully observed and recorded. A canine patient with biopsy-confirmed adenocarcinoma of the prostate gland, suspected local invasion, and distant metastasis underwent a [⁶⁸Ga]PSMA-11 PET/CT scan with an injected activity of 91MBq. Imaging of the whole body commenced at 60 minutes post-injection. 24 hours after initial imaging was performed a secondary scan commenced, an injection of 132MBq of [⁶⁴Cu]HBP-PSMA was administered, followed by immediate 60-minute list-mode dynamic PET/CT over the region of the liver/spleen to assess organ clearance. Whole-body images were then obtained at 1, 24 and 48 hours post-injection. The canine patient then underwent a secondary biopsy to determine a suitable target receptor for further imaging studies. Upon biopsy confirmation, a [⁶⁴Cu]HBP-EGFR PET/CT was performed, whereby 128MBq of activity was injected with whole-body imaging commencing 24 and 48 hours post-injection.

Results: Both the [⁶⁸Ga]PSMA-11 and [⁶⁴Cu]HBP-PSMA were unable to detect the presence of prostate carcinoma despite the heterogeneous appearance of the prostate gland on the low dose CT scan performed in conjunction with the PET. The subsequent biopsy of the prostate gland revealed that the tumour was Prostate-Specific Membrane Antigen negative. Further analysis revealed an overexpression of Epidermal Growth Factor Receptor, which is frequently associated with aggressive forms of prostate cancer.^[4] PET/CT imaging using the more specific target [⁶⁴Cu]HBP-EGFR was able to positively identify 2 lesions within the prostate gland with an SUV_max of 4.11 and 3.76, compared to the SUV_mean observed in the liver of 1.19 at 24 hours post-injection. The findings in the whole-body PET/CT confirmed pharmacokinetics/distribution patterns similar to those observed in mice studies. No nodal or distant metastases were identified using [⁶⁴Cu]HBP-EGFR. Conclusion: PET/CT has proven to be an effective tool in guiding the use of specific targets for drug delivery to spontaneously occurring disease. The result of this work validates results shown in previous mice studies. Comparative oncology enables researches to further understand the mechanisms of human disease and fast-track drug development. The utility of HBP as a transport mechanism for chemotherapy drugs using PET/CT to determine personalised targets is currently being investigated in canine models.

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