Objective. Utilizing prompt gammas in preclinical pinhole-collimated positron emission tomography (PET) avoids image degradation due to positron range blurring and photon down scatter, enables multi-isotope PET and can improve counting statistics for low-abundance positron emitters. This was earlier reported for 124I, 89Zr and simultaneous 124I −18F PET using the VECTor scanner (MILabs, The Netherlands), demonstrating sub-mm resolution despite long positron ranges. The aim of the present study is to investigate if such sub-mm PET imaging is also feasible for a large variety of other isotopes including those with extremely high energy prompt gammas (>1 MeV) or with complex emission spectra of prompt gammas. Approach. We use Monte Carlo simulations to assess achievable image resolutions and uniformity across a broad range of spectrum types and emitted prompt gamma energies (603 keV–2.2 MeV), using 52Mn, 94Tc, 89Zr, 44Sc, 86Y, 72As, 124I, 38K, and 66Ga. Main results. Our results indicate that sub-millimeter resolution imaging may be feasible for almost all isotopes investigated, with the currently used cluster pinhole collimators. At prompt gamma energies of 603 keV of 124I, an image resolution of ∼0.65 mm was achieved, while for emissions at 703, 744, 834, and 909 keV of 94Tc, 52Mn, 72As, and 89Zr, respectively, ∼0.7 mm resolution was obtained. Finally, at ultra-high energies of 1.2 (44Sc) and 1.4 MeV (52Mn) resolutions of ∼0.75 mm and ∼0.8 mm could still be achieved although ring artifacts were observed at the highest energies (1.4 MeV). For 38K (2.2 MeV), an image resolution of 1.2 mm was achieved utilizing its 2.2 MeV prompt emission. Significance. This work shows that current cluster pinhole collimators are suitable for sub-mm resolution prompt PET up till at least 1.4 MeV. This may open up new avenues to developing new tracer applications and therapies utilizing these PET isotopes.

Objective. Advanced pinhole collimation geometries optimized for preclinical high-energy ɣ imaging facilitate applications such as ɑ and ß emitter imaging, simultaneous multi-isotope PET and PET/SPECT, and positron range-free PET. These geometries replace each pinhole with a group of clustered pinholes (CPs) featuring smaller individual pinhole opening angles (POAs), enabling sub-mm resolution imaging up to ∼1 MeV. Further narrowing POAs while retaining field-of-view (FOV) may enhance high-energy imaging but faces geometrical constraints. Here, we detail how the novel twisted CPs (TCPs) address this challenge. Approach. We compared TCP and CP collimator sensitivity at equal system resolution (SR) and SR at matched sensitivity by tuning pinhole diameters for 18F (511 keV) and 89Zr (909 keV). Additionally, simulated Derenzo phantoms at low activity (LA: 12 MBq ml−1) and high activity (HA: 190 MBq ml−1) levels, along with uniformity images, were compared to assess image resolution and uniformity. Main results. At equal SR, TCP increased average central FOV sensitivity by 15.6% for 18F and 29.4% for 89Zr compared to CP. Image resolution was comparable, except for 89Zr at LA, where TCP resolved 0.80 mm diameter rods compared to 0.90 mm for CP. Image uniformity was equivalent for 18F, while for 89Zr TCP granted a 10.4% improvement. For collimators with matched sensitivity, TCP improved SR by 6.6% for 18F and 17.7% for 89Zr while also enhancing image resolution; for 18F, rods distinguished were 0.65 mm (CP) and 0.60 mm (TCP) for HA, and 0.70 mm (CP and TCP) for LA. For 89Zr, image resolutions were 0.75 mm (CP) and 0.65 mm (TCP) for HA, and 0.90 mm (CP) and 0.80 mm (TCP) for LA. Image uniformity with TCP decreased by 18.3% for 18F but improved by 20.1% for 89Zr. Significance. This study suggests that the TCP design has potential to improve high-energy ɣ imaging.