Imaging Cobalamin Uptake within Malignant Breast Tumors In Vivo

To image the uptake of cobalamin (Cbl) within malignant breast tumors in vivo.

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.

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.

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.