Imaging Cobalamin Uptake within Malignant Breast Tumors In Vivo.

PURPOSE: To image the uptake of cobalamin (Cbl) within malignant breast tumors in vivo. PROCEDURES: Prior to surgery 20 female patients with clinically suspected breast tumors were intravenously administered 0.25 μg of an In-111 labeled 5-deoxyadenosylcobalamin (AC) analog ([111In]AC) and sequentially imaged with whole-body planar (WBP) and single-photon emission computed tomography (SPECT) between 2-5 h and 20-24 h post-injection (P.I.). The tumor to background (T/B) ratio for [111In]AC in breast tumors at 2-5 h was correlated to its expression of estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors. Subsequent pulse chase (PC) experiments in nude mice burdened with the MDA-MB-231 triple-negative (TN) breast tumor xenograft measured the effect that pulses of AC or dexamethasone (DEX) had on [111In]AC uptake in both normal murine tissue and the TN breast tumor.
RESULTS: The mean [111In]AC T/B ratio of the patients' 18 resected tumors was 5.8. Comparing ER- and PR-positive tumors (n = 11) to TN and HER2-positive tumors (n = 7), the mean [111In]AC T/B ratios at 2-5 h P.I. were 3.2 (range 1.8-5.6) and 10.4 (range 3.3-22.5), respectively. Pulses of 2.0 μg of AC at 2, 8, or 24 h; or 40.0 μg of DEX at 24 h prior to injecting 0.5 μg of [111In]AC, increased mean tracer uptake in the MDA-MB-231 tumors by 26.4, 71.5, 92.6, and 49.1 %, respectively. Only the 2- and 24-h PC intervals concomitantly suppressed [111In]AC uptake in normal murine tissue while enhancing [111In]AC uptake in MDA-MB-231 tumors.
CONCLUSION: The uptake of Cbl within malignant breast tumors can be imaged clinically. Cbl uptake is greatest in TN and HER2-positive breast tumors. A solitary bolus of AC or DEX increases the [111In]AC uptake within a breast tumor in vivo. Investigating the cytogenetic mechanisms controlling the endocytosis of Cbl in malignant breast tumors is warranted.