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

Abstract

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.