title: Tumor imaging in patients with advanced tumors using a new (99m) Tc-radiolabeled vitamin B12 derivative.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Division of Nuclear Medicine, Department Medical Radiology, University Hospital of Zurich, Zurich, Switzerland.
authors: Bert-Ram
authors: BR
authors: Sah
authors: Roger
authors: R
authors: Schibli
authors: Robert
authors: R
authors: Waibel
authors: Lotta
authors: L
authors: von Boehmer
authors: Peter
authors: P
authors: Bläuenstein
authors: Ebba
authors: E
authors: Nexo
authors: Anass
authors: A
authors: Johayem
authors: Eliane
authors: E
authors: Fischer
authors: Ennio
authors: E
authors: Müller
authors: Jan D
authors: JD
authors: Soyka
authors: Alexander K
authors: AK
authors: Knuth
authors: Stefan K
authors: SK
authors: Haerle
authors: Pius August
authors: PA
authors: Schubiger
authors: Niklaus G
authors: NG
authors: Schaefer
authors: Irene A
authors: IA
authors: Burger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000000981:diagnostic imaging*; D015609:Organotechnetium Compounds / Q000494:pharmacology*; D011446:Prospective Studies; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013667:Technetium / Q000494:pharmacology*; D013997:Time Factors; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D051598:Whole Body Imaging
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C586678:technetium 99m tricarbonyl-((4-amidobutyl)pyridin-2-ylmethylaminoacetato)cobalamin; D013667:Technetium; D014805:Vitamin B 12
keywords: cancer; cobalamin; haptocorrin; transcobalamin receptors; vitamin B12