Progesterone receptors (PRs) are present in many breast tumors, and their levels are increased by certain endocrine therapies. We describe the synthesis and PR binding affinities of a series of bromine- and iodine-substituted 16α,17α-dioxolane progestins, some of which, when appropriately radiolabeled, are potential agents for diagnostic imaging of PR-positive breast tumors using positron emission tomography (PET) and for radiotherapy. These compounds were synthesized from halogenated furanyl, phenyl, and thiophenyl aldehydes and a progestin 16α,17α,21-triol (5) in the presence of HClO4 or Sc(OTf)3 in high yields under optimized conditions. A new reagent, perfluoro-1-butanesulfonyl fluoride (PBSF), was used to convert the C-21 OH to F in high yields. The relative binding affinities (RBAs) of the most promising compounds for the PR (RBA of R5020 = 100) were 16α,17α-[(R)-1′-α-(5-bromofurylmethylidene)dioxyl] -21-hydroxy-19-norpregn-4-ene-3,20-dione (endo-6; RBA = 65 and moderate lipophilicity), 21-fluoro-16α,17α-[(R)-1′-α-(5- iodofurylmethylidene)dioxyl]-19-norpregn-4-ene-3,20-dione (endo-14; RBA = 40) and 21-fluoro-16α,17α-[(S)-1′-β-(-iodophenylmethylidene) dioxyl]-19-norpregn-4-cne-3,20-dione (exo-16; RBA = 34).