Biosensor imaging of redundant deviation
in shifts (BIRDS) is a
molecular imaging platform for magnetic resonance that utilizes unique
properties of low molecular weight paramagnetic monomers by detecting
hyperfine-shifted nonexchangeable protons and transforming the chemical
shift information to reflect its microenvironment (e.g., via temperature,
pH, etc.). To optimize translational biosensing potential of BIRDS
we examined if this detection scheme observed with monomers can be
extended onto dendrimers, which are versatile and biocompatible macromolecules
with modifiable surface for molecular imaging and drug delivery. Here
we report on feasibility of paramagnetic dendrimers for BIRDS. The
results show that BIRDS is resilient with paramagnetic dendrimers
up to the fourth generation (i.e., G1–G4), where the model
dendrimer and chelate were based on poly(amido amine) (PAMAM) and
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA<sup>4–</sup>) complexed with thulium ion (Tm<sup>3+</sup>). Temperature
sensitivities of two prominent signals of G<i>n</i>-PAMAM-(TmDOTA<sup>–</sup>)<sub><i>x</i></sub> (where <i>n</i> = 1–4, <i>x</i> = 6–39) were comparable
to that of prominent signals in TmDOTA<sup>–</sup>. Transverse
relaxation times of the coalesced nonexchangeable protons on Gn-PAMAM-(TmDOTA<sup>–</sup>)<sub><i>x</i></sub> were relatively short
to provide signal-to-noise ratio that was comparable to or better
than that of TmDOTA<sup>–</sup>. A fluorescent dye, rhodamine,
was conjugated to a G2-PAMAM-(TmDOTA)<sub>12</sub> to create a dual-modality
nanosized contrast agent. BIRDS properties of the dendrimer were unaltered
with rhodamine conjugation. Purposely designed paramagnetic dendrimers
for BIRDS in conjunction with novel macromolecular surface modification
for functional ligands/drugs could potentially be used for biologically
compatible theranostic sensors