Evaluation of a bromine-76-labeled progestin 16α,17α-dioxolane for breast tumor imaging and radiotherapy: in vivo biodistribution and metabolic stability studies

Abstract

Introduction-Progesterone receptors (PRs) are present in many breast tumors, and their levels are increased by certain endocrine therapies. They can be used as targets for diagnostic imaging and radiotherapy. Results-[ 76 Br]3 was synthesized in 5% overall yield with specific activity being 200~1250 Ci/ mmol. [ 76 Br]3 demonstrated high PR-mediated uptake in the target tissue uterus (8.72 ± 1.84 %ID/ g at 1 h) that was reduced by a blocking dose of unlabeled progestin R5020, but the non-specific uptake in blood and muscle (2.11 ± 0.14 and 0.89 ± 0.16 %ID/g at 1 h, respectively) was relatively high. [ 76 Br]3 was stable in whole rat blood in vitro, but it was not stable in vivo due to the fast metabolism that occurred in the liver, resulting in the formation of a more polar radioactive metabolite and free [ 76 Br]bromide. The level of free [ 76 Br]bromide in blood remained high during the experiment (2.11 ± 0.14 %ID/g at 1 h and 1.52 ± 0.24 %ID/g at 24 h). The tissue distribution of [ 76 Br]3 at 1 and 3 hours was compared with that of the 18 F analogs, [ 18 F]FFNP 1 and ketal 2. Method-16α,17α-[(R)-1'-α-(5-[ Conclusion-[76 Br]3 may have potential for imaging PR positive breast tumors at early time points, but it is not suitable for imaging at later times or for radiotherapy.

Longitudinal Noninvasive Imaging of Progesterone Receptor as a Predictive Biomarker of Tumor Responsiveness to Estrogen Deprivation Therapy

“…The IC 50 of Dex for GR in rat lung is 0.1 μM whereas the IC 50 of R5020 for PgR in sheep uterus is 0.05 μM (19). Blocking doses were determined based on the IC 50 ’s and published results (20, 21). 0.5 μmol of Dex or 0.055 μmol of R5020 was injected into SSM3-bearing mice immediately prior to the injection of [ 18 F]FFNP.…”

Bromination from the Macroscopic Level to the Tracer Radiochemical Level: 76Br Radiolabeling of Aromatic Compounds via Electrophilic Substitution

“…[ 76 Br] 3 was used in the synthesis of a 76 Br-labeled progestin 16α,17α-dioxolane for breast tumor imaging and radiotherapy (42). Four hours of premixing of 2:1 H 2 O 2 /ACOH was necessary to make enough PAA to afford a high yield of bromination product 3 (Table 5).…”

Mapping biological behaviors by application of longer-lived positron emitting radionuclides

“…Because of the faster excretion of 125 I, the concentration of 125 I in urine samples was three times higher than that of 76 Br during the first day [10]. Interestingly, 76 Br-labeled small molecules also released free bromide in vivo and showed high non-specific uptake in blood [67]. …”