New vitamin B12 cancer biomarker on the block
An investigative SPECT/CT imaging agent targets tumor cells via a vitamin B12 carrier, according to research published online Dec. 12 by the Journal of Nuclear Medicine.
Bert-Ram Sah, a researcher from the division of nuclear medicine and department of medical radiology at the University Hospital of Zurich, Switzerland, and colleagues evaluated the feasibility of SPECT/CT imaging with the novel compound, technetium-99m (CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino]-acetato] cobalamin (Tc-99mPAMA-cobalamin). Previous formulas had been unsuccessful due to unwanted tissue uptake by way of transcobalamin, which facilitates B12 bioavailability.
The newest version of the agent bypasses transcobalamin but still binds to the expression of the protein haptocorrin, which acts to protect the vitamin from stomach acid. In this study, researchers developed a way to optimize tumor-binding by preventing healthy tissue uptake from transcobalamin and haptocorrin.
“After pretreatment with cobalamin to saturate circulating haptocorrin, the tracer accumulates in tumor tissue, liver, and salivary glands but not in the radiosensitive kidneys,” wrote Sah et al. “Although the overall sensitivity was low, compared with F-18 FDG PET/CT, the present results may pave the road for further development of radiotherapeutic drugs.”
A total of 10 patients with a variety of metastatic tumors were imaged with SPECT/CT and Tc-99m PAMA-cobalamin to test the agent’s tumor-binding ability. Results of the study showed that six out of 10 patients had positive tumor uptake upon whole body imaging. Of these, three patients had lung adenocarcinomas, one had breast adenocarcinomas, one patient had colon adenocarcinoma and one had hypopharyngeal squamous cell carcinoma.
“Because of the small numbers and the heterogeneity of our study, we could not determine any disease-specific sensitivities or specificities for Tc-99m PAMA-cobalamin,” wrote the researchers. “Nevertheless, it is the first study in humans confirming that selective tumor imaging with Tc-99m PAMA-cobalamin is feasible in a large variety of different tumor histologies and shows a low renal uptake.”
The agent is not yet approved for clinical cancer screening. Further studies are required to validate its benefit as an oncologic imaging agent.