Cyclotron production of 206Bi for SPECT tracing of bismuth radioisotopes' redistribution in vivo.

Targeted α-therapy (TAT) is a promising therapeutic strategy for advanced cancers, but redistribution of short-lived daughter radionuclides remains a key challenge. This is particularly true for 225Ac and 212Pb, whose decay chains both include α-emitting bismuth isotopes that are difficult to image directly. Production and subsequent radiochemical isolation of 206Bi (t1/2 = 6.24 d, 100% EC+β+) was investigated as a SPECT-imaging surrogate for 212/213Bi, alpha-emitting daughters of 225Ac and 212Pb. Isotopically enriched 206PbO targets were irradiated with 11.9 MeV protons to access the 206Pb(p,n)206Bi nuclear reaction on a 16 MeV GE PETtrace cyclotron. Following target dissolution in nitric acid, 206Bi separates from 206Pb using branched-DGA resin, achieving efficient Pb/Bi separation and recovery of enriched 206Pb for subsequent irradiation. The irradiation yielded 1.9 ± 0.2 MBq/μAh of 206Bi (n = 4), with a decay-corrected radiochemical yield of 96.6 ± 2.6% (n = 4), 206Pb recycling efficiency of 95.3 ± 1.5% (n = 8), and high chemical and radionuclidic purity (>99.88%). Preclinical SPECT/CT imaging of a Derenzo phantom documents a 1.03 mm spatial resolution, and first in vivo SPECT/CT imaging records preferential renal uptake of unchelated 206Bi in ICR mice. These results establish a practical production route for 206Bi and demonstrate its potential as preclinical SPECT tracer for investigating radiobismuth biodistribution relevant to alpha-emitter daughters redistribution.