*2.1. Ho Target Preparation and Irradiation*

Cyclotron targets were prepared from holmium metal foils. Initially, 300–640 µm thick holmium foils (99.9%, Alfa Aesar, Haverhill, MA, USA) were used. Based on certificates of analysis, two differing foil lots contained 0.06% (600 ppm) or <0.01% (<100 ppm) erbium. High-purity 0.5 mm-thick, 10 mm diameter holmium metal discs with 0.5 ppm Er were purchased from the U.S. Department of Energy (DOE) Ames Laboratory Materials Preparation Center (MPC), Ames, IA, USA. Based on proton energy loss calculations [44], a 300 µm holmium degrades 12.5 MeV protons to 7.1 MeV, below which the <sup>165</sup>Ho(*p,n*) <sup>165</sup>Er nuclear reaction cross-section vanishes [24]. Holmium foils were wrapped in 25 µm stainless steel foil and rolled to desired thickness (190–400 µm) using a commercial rolling mill. A commercial disc cutter (Pepetools) was used to punch holmium discs of desired diameter (3–9.5 mm). The holmium target disc was centered and spot-welded to a 0.5 mm-thick, 19 mm diameter tantalum disc using a variable transformer-controlled (60–75% power) commercial 115 V spot welder fitted with a copper or silver electrode as previously described [45]. Roughly 6–10 individual spot welds uniformly cover the 7 to 70 mm<sup>2</sup> holmium target.

Spot-welded holmium metal targets were proton irradiated at the University of Wisconsin using two biomedical cyclotrons—an RDS-112 (CTI Cyclotron Systems, Knoxville, TN, USA) and a PETtrace (GE Healthcare, Uppsala, Sweden). For RDS-112 irradiations, the target disc was clamped to a water-jet-cooled target support fixture with a 12.7 mm apertured aluminum ring and irradiated with 10–20 µA of undegraded 11 MeV protons. For PETtrace irradiations, a commercial solid target irradiation and transfer system (ARTMS QIS, Vancouver, BC, Canada) was used. Holmium targets discs were assembled into the water-jet cooled transfer capsule, positioned 3.6 cm down-beam from a water-cooled 500 µm thick aluminum degrader, and irradiated with 20–40 µA of 12.5 MeV protons.

For low intensity irradiations, <sup>165</sup>Er was quantified by high-purity germanium (HPGe) gamma spectrometry (full width at half maximum at 1333 keV = 1.6 keV, Canberra Inc., Meriden, CT, USA) of the irradiated target disc, while correcting for the self-attenuation of the 46–55 keV x-rays. The HPGe low energy range (30–300 keV) was efficiency calibrated using <sup>133</sup>Ba and <sup>241</sup>Am calibration standards (Amersham, United Kingdom).
