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Potential of PET in oncology and radiotherapy

Clatterbridge Centre for Oncology, Wirral, UK

View larger version (85K): [in a new window]   Figure 1. Typical transabdominal CT (a) and corresponding 11C-DACA (N-[2-(dimethylamino)ethyl]acridine-4-carboxamide) PET images demonstrating radiotracer uptake in kidneys, spleen and renal tumour (b). Uptake of radiotracer is also seen in the heart, myocardium and mesothelioma (c) and gliomas (d). Kindly reproduced with permission from: Saleem A, Harte R, Matthews J, Osman S, Brady F, Luthra S et al. Pharmacokinetic evaluation of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in patients by positron emission tomography. J Clin Oncol 2001;19:1421–9.

View larger version (32K): [in a new window]   Figure 2. 11C-DACA (N-[2-(dimethylamino)ethyl]acridine-4-carboxamide) time–activity curves for various tissues and tumour in the pre-phase I study group. The time–activity curves were corrected for decay and normalised for the injected activity per body surface area. Kindly reproduced with permission from: Saleem A, Harte R, Matthews J, Osman S, Brady F, Luthra S, et al. Pharmacokinetic evaluation of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in patients by positron emission tomography. J Clin Oncol 2001;19:1421–9.

View larger version (11K): [in a new window]   Figure 3. A significant decrease (p<0.05) in myocardial 11C-radiotracer exposure (area under the time–activity curve (AUC)) with phase I compared with pre-phase I doses of DACA (N-[2-(dimethylamino)ethyl]acridine-4-carboxamide) demonstrated myocardial saturation. However, a significant increase in tumour exposure was seen, signifying a lack of tumour saturation with the 3-h infusion of DACA.

View larger version (10K): [in a new window]   Figure 4. Area under the time–activity curve (AUC) of 11C-DACA (N-[2-(dimethylamino)ethyl]acridine-4-carboxamide) PET scan prior to and after 120-h infusion of DACA at the maximum tolerated dose (MTD). The lack of substantial change implies that there is no evidence of a saturable process either systemically or within the tumour, despite reaching the MTD.

View larger version (9K): [in a new window]   Figure 5. 11C-temozolomide-PET studies demonstrating that a higher area under the time–activity curve (AUC) was reached in tumours compared with normal brain.

View larger version (15K): [in a new window]   Figure 6. Temozolomide was tissue specific but did not demonstrate tumour-specific activity; there was no difference between the percentage of ring opening that occurred in tumours compared with normal tissue.

View larger version (18K): [in a new window]   Figure 7. Percentage changes in tumour perfusion with combretastatin (CA4P) at (A) 30 min and (B) 24 h after infusion. A threshold response is clearly seen. Kindly reproduced with permission from: Anderson H, Yap J, Miller M, Robbins A, Jones T, Price P. Assessment of pharmacodynamic vascular response in a Phase I trial of combretastatin A4 phosphate. J Clin Oncol 2003;21:2823–30.

View larger version (9K): [in a new window]   Figure 8. Changes in perfusion at 24 h after intravenous combretastatin were reversed in normal tissue, whilst tumour perfusion was non-reversible at 24 h.

View larger version (73K): [in a new window]   Figure 9. Typical transabdominal CT scan (a), and corresponding PET blood flow (b), and [18F]5-fluorouracil images without eniluracil (c) and with eniluracil (d), showing liver, spleen and multiple liver metastases.

View larger version (65K): [in a new window]   Figure 10. Temporal representation of 18F-radiotracer localisation in a selected transabdominal plane passing through the liver after the injection of [18F]5-fluorouracil without eniluracil (A) and after eniluracil (B). Kindly reproduced with permission from: Saleem A, Yap J, Osman S, Brady F, Suttle B, Lucas SV, et al. Modulation of fluorouracil tissue pharmacokinetics by eniluracil: in-vivo imaging of drug action. Lancet 2000;355:2125–31.

View larger version (57K): [in a new window]   Figure 11. Fluorodeoxyglucose (FDG)-PET response seen in a brain tumour after 7 days, and corresponding CT changes at 2 months. Kindly reproduced with permission from: Aboagye E, Saleem A, Price P. Tumor imaging applications in the testing of new drugs. In: Baguley B, Kerr D, editors. Anticancer drug development. London, UK: Academic Press, 2002.

View larger version (63K): [in a new window]   Figure 12. Response in a patient with Ewing's sarcoma assessed with 11C-thymidine PET. Kindly reproduced with permission from: Gupta N, Price P, Aboagye E. PET for in vivo pharmacokinetic and pharmacodynamic measurements. Eur J Cancer 2002;38:2094–107.