Biodistribution of Radiolabeled Adenosylcobalamin in Patients Diagnosed With Various Malignancies

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Objective

To study the biodistribution of a vitamin Bl2 analog, indium In 1ll-labeled diethylenetriaminepentaacetate adenosylcobalamin (In 111 DAC), in patients recently diagnosed as having primary or recurrent malignancy.

Patients and Methods:

Thirty patients (14 women and 16 men) with radiographically or clinically diagnosed breast, lung, colon, sarcomatous, thyroid, or central nervous system malignancies were studied prior to definitive surgery or biopsy. A maximum of 650 µCi (2.2 µg) of In 111 DAC was administered intravenously. Vitamin Bl2 and folate levels were determined prior to injection. Serum clearance and urinary and stool excretion of the tracer were measured. Images were routinely obtained at 0.5, 3 to 5, and 20 to 24 hours after injection. Biodistribution of In 111 DAC was determined by computer analysis of regions of interest.

Results:

Serum Tl/2 clearance was 7 minutes. Average urinary and stool excretion of the injected dose over 24 hours was 26.1% and 0.4%, respectively. The greatest focal uptake of In 111 DAC occurred in the liver and spleen, followed by the nasal cavity and salivary and lacrimal glands. The average tumor uptake of the injected dose was 2% at 30 minutes and 1.5% at 24 hours. High-grade primary and metastatic breast, lung, colon, thyroid, and sarcomatous malignancies were all imaged at 3 to 5 hours after injection. Central nervous system tumors and advanced metastatic prostate cancer were best identified at 24 hours. Mammographically occult, palpable, and nonpalpable breast cancers were delineated by In 111 DAC. Low-grade malignancies as well as early skeletal metastatic disease were not effectively imaged by the vitamin Bl2 tracer. Patients with elevated baseline vitamin Bl2 or those concurrently taking corticosteroids appeared to have optimal visualization of their malignancies.

Conclusion:

Vitamin Bl2 may be a useful vehicle for delivering diagnostic and therapeutic agents to various malignancies. Further evaluation of cobalamin analogs and their interaction with transport proteins and cellular receptors within malignant tissue and infection is warranted.

Section snippets

Patients

After receiving approval from the Mayo Clinic Institutional Review Board and the Radioactive Drug Research Committee, we enrolled 30 patients with radiographically or clinically diagnosed breast, lung, colon, sarcomatous,

Synthesis and Analysis of DAC

The synthesis of DAC has been described previously.2 Mass spectrometry (MS) data were obtained on a Sciex Atmospheric Pressure Ionisation 365 mass spectrometer (Toronto, Ontario). Separations were carried out using online high-pressure liquid chromatography (HPLC) consisting of

Patients

Patients were enrolled over a 9-month interval (January-September 1999). Of the 30 patients studied, 14 were women and 16 were men. The median age (range) was 59.9 years (36–80 years) for the women and 56.4 years (19–81 years) for the men. Of the women studied, 9 were evaluated for breast cancer, 2 for sarcomatous lesions (leiomyosarcoma, osteogenic sarcoma), 2 for thyroid malignancies (anaplastic, medullary), and 1 for presumed lung cancer. Of the 16 men enrolled, 4 had presumed lung cancers,

Overview of Vitamin B12 Chemistry

The colored organometallic tetrapyrole compounds are essential for life.3 Pernicious anemia or lack of vitamin B12 in humans is a case in point. Adenosylcobalamin is the mitochondrial coenzyme for methylmalonyl-coenzyme A (CoA) mutase. This coenzyme is ultimately responsible for the conversion of the amino acids methionine, threonine, isoleucine, and valine, any odd chain fatty acids, and proprionyl CoA to succinyl CoA. Subsequently succinyl CoA enters into the tricarboxylic acid (Krebs) cycle

Conclusions

The findings in the first 30 patients studied with In 111 DAC demonstrated that the biodistribution of the vitamin B12 analog was similar between the sexes. There is rapid serum clearance and marked urinary excretion of the analog. The optimal imaging time for tumors appears to be 3 to 5 hours after injection of the tracer, with the exception of 24 hours for primary CNS tumors, advanced metastatic prostate disease, and Htirthle cell thyroid cancer. In the various types of malignancies imaged,

Acknowledgment

The authors thank Rose M. Busta for preparation of the manuscript.

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    This study was supported in part by the Mayo Foundation and the University of Minnesota.

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