Sah, Bert-Ram2; Schibli, Roger3; Waibel, Robert3; von Boehmer, Lotta3; Bläuenstein, Peter3; Nexo, Ebba4; Johayem, Anass3; Fischer, Eliane3; Müller, Ennio3; Soyka, Jan D3; Knuth, Alexander K3; Haerle, Stefan K3; Schubiger, Pius August3; Schaefer, Niklaus G3; Burger, Irene A3
1 Department of Clinical Medicine - Clinical Biochemistry, Department of Clinical Medicine, Health, Aarhus University2 Division of Nuclear Medicine, Department Medical Radiology, University Hospital of Zurich, Zurich, Switzerland.3 unknown4 Department of Clinical Medicine - Clinical Biochemistry, Department of Clinical Medicine, Health, Aarhus University
Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new (99m)Tc-cobalamin derivative ((99m)Tc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin, (99m)Tc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is recognized by haptocorrin, a protein present in the circulation and notably expressed in many tumor cells. In this prospective study, we investigated cancer-specific uptake of (99m)Tc-PAMA-cobalamin in 10 patients with various metastatic tumors. METHODS: Ten patients with biopsy-proven metastatic cancer were included. Dynamic imaging was started immediately after injection of 300-500 MBq of (99m)Tc-PAMA-cobalamin, and whole-body scintigrams were obtained at 10, 30, 60, 120, and 240 min and after 24 h. The relative tumor activity using SPECT/CT over the tumor region after 4 h was measured in comparison to disease-free lung parenchyma. Patients 3-10 received between 20 and 1,000 μg of cobalamin intravenously before injection of (99m)Tc-PAMA-cobalamin. The study population comprised 4 patients with adenocarcinomas of the lung, 3 with squamous cell carcinomas of the hypopharyngeal region, 1 with prostate adenocarcinoma, 1 with breast, and 1 with colon adenocarcinoma. RESULTS: The median age of the study group was 61 ± 11 y. Six of 10 patients showed positive tumor uptake on (99m)Tc-PAMA-cobalamin whole-body scintigraphy. The scan was positive in 1 patient with colon adenocarcinoma, in 3 of 4 lung adenocarcinomas, in 1 of 3 hypopharyngeal squamous cell carcinomas, and in 1 breast adenocarcinoma. Renal uptake was between 1% and 3% for the left kidney. Predosing with cobalamin increased the tumor uptake and improved blood-pool clearance. The best image quality was achieved with a predose of 20-100 ug of cold cobalamin. The mean patient dose was 2.7 ± 0.9 mSv/patient. CONCLUSION: To our knowledge, we report for the first time on (99m)Tc-PAMA-cobalamin imaging in patients with metastatic cancer disease and show that tumor targeting is feasible.
Journal of Nuclear Medicine, 2014, Vol 55, Issue 1, p. 43-9