Oncology
The development of imaging compounds to detect and treat a range of cancers is a priority.
There is a higher incidence of Melanoma in Australia than other countries and, in New South Wales, it is the fourth most common cancer. While localised melanoma has a high survival rate, metastatic disease has no effective treatment, and effective treatments are needed. For imaging of melanoma lesions to determine spread, 18F-FDG has a high sensitivity/specificity. In cases where there is high clinical suspicion of metastatic disease, but the patients images are FDG-negative, compounds which localise by an alternate mechanism could be useful.
Pancreatic cancer is a very difficult cancer to detect and treat. The five-year survival rate in the US is <4% and in NSW, it is 7%. In the US, it is the fourth leading cause of death. Surgery is the only cure, but only 20% of patients are eligible for surgery. Even after surgery, the five-year survival rate is only 20%. Standard diagnostic modalities are not effective for preoperative diagnosis and this impinges on surgical decisions. FDG may provide the answer as a physiological means of diagnosis, primary and metastases. However, effective treatments are needed.
Breast cancer is the second leading cause of cancer death for women in the US. While most women present with localised disease, a significant fraction (20%) present with metastases. Women with localised disease have a high (~80% over five year) survival rate. However, in those with metastatic disease, only 20% survive longer than five years. Again, additional treatments would aid these patients.
Prostate cancer is the fifth leading cause of death in the US. It usually strikes men over 65 yr (220,000 new cases a year). Screening is done using the presence of prostate specific antigen in the blood. Biopsy is used to make the diagnosis. At initial diagnosis, the Gleason score, a histological measure of the cancer aggressiveness, is used for surgical decisions. After prostate removal, the blood prostate specific antigen is used to detect recurrence. Standard diagnostic modalities are ineffective in detecting most prostate cancer lesions. In the US, an 111In labelled antibody is used to determine soft tissue metastatic disease but has a modest sensitivity/specificity (65-70%). A prostate cancer specific PET imaging agent could improve initial staging and managing recurrence. Eventually, all prostate cancer patients become refractory to hormone treatment. For these patients, chemotherapy is ineffective and alternative treatments are needed.
A number of small molecule high affinity σ2-directed vectors have been synthesized. There is good previous experience with animal models of breast and prostate cancer. However, at present experiments with σ2-directed vectors in prostate cancer animal models have been delayed due to the unavailability of the animal involved.