Overexpression of folate receptors (FRs) on different tumor types (e.g., ovarian, lung) make FRs attractive in vivo targets for directed diagnostic/therapeutic agents. Currently, no diagnostic agent suitable for positron emission tomography (PET) has been adopted for clinical FR imaging. In this work, two ⁵⁵Co-labeled albumin-binding folate derivatives-[⁵⁵Co]Co-cm10 and [⁵⁵Co]Co-rf42-with characteristics suitable for PET imaging have been developed and evaluated. High radiochemical yields (≥95%) and in vitro stabilities (≥93%) were achieved for both compounds, and cell assays demonstrated FR-mediated uptake. Both ⁵⁵Co-labeled folate conjugates demonstrated high tumor uptake of 17% injected activity per gram of tissue (IA/g) at 4 h in biodistribution studies performed in KB tumor-bearing mice. Renal uptake was similar to other albumin-binding folate derivatives, and liver uptake was lower than that of previously reported [⁶⁴Cu]Cu-rf42. Small animal PET/CT images confirmed the biodistribution results and showed the clear delineation of FR-expressing tumors.

Accurate gain control of PET detectors is a prerequisite for quantitative accuracy. A shift in the 511 keV peak position can lead to errors in scatter correction, degrading quantitation. The PET detectors in a PET/MR scanner are subject to thermal transients due to eddy currents induced during gradient-intensive MRI sequences. Since the gain of silicon photomultiplier-based detectors changes with temperature, good gain control is particularly challenging. In this paper we describe a method that utilizes information from the entire singles spectrum to create a real-time gain control method that maintains gain of PET detectors stable within approximately ±0.5% (±2.5 keV) with varying levels of scatter and in the presence of significant thermal transients. We describe the methods used to combine information about multiple peaks and how this algorithm is implemented in a way that permits real-time processing on a field-programmable gate array. Simulations demonstrate rapid response time and stability. A method (“virtual scatter filter”) is also described that extracts unscattered photopeak events from phantom data and demonstrates the accuracy of the photopeak for various radionuclides that emit energies in addition to the pure 511 keV annihilation peak. Radionuclides 52Mn, 55Co, 64Cu, 89Zr, 90Y, and 124I are included in the study for their various forms of spectral contamination.