A first-in-human study of [68Ga]Ga-CDI: a positron emitting radiopharmaceutical for imaging tumour cell death.

PURPOSE: This study assesses human biodistribution, radiation dosimetry, safety and tumour uptake of cell death indicator labelled with 68Ga ([68Ga]Ga-CDI), a novel radiopharmaceutical that can image multiple forms of cell death. METHODS: Five participants with at least one extracranial site of solid malignancy > 2 cm and no active cancer treatment in the 8 weeks prior to the study were enrolled. Participants were administered 205 ± 4.1 MBq (range, 200-211 MBq) of [68Ga]Ga-CDI and 8 serial PET scans acquired: the first commencing immediately and the last 3 h later. Participants were monitored for clinical, laboratory and electrocardiographic side effects and adverse events. Urine and blood radioactivity was measured. Spherical volumes of interest were drawn over tumour, blood pool and organs to determine biodistribution and calculate dosimetry. In one participant, tumour specimens were analysed for cell death using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining. RESULTS: [68Ga]Ga-CDI is safe and well-tolerated with no side effects or adverse events. [68Ga]Ga-CDI is renally excreted, demonstrates low levels of physiologic uptake in the other organs and has excellent imaging characteristics. The mean effective dose was 2.17E - 02 ± 4.61E - 03 mSv/MBq. It images constitutive tumour cell death and correlates with tumour cell death on histology. CONCLUSION: [68Ga]Ga-CDI is a novel cell death imaging radiopharmaceutical that is safe, has low radiation dosimetry and excellent biodistribution and imaging characteristics. It has potential advantages over previously investigated radiopharmaceuticals for imaging of cell death and has progressed to a proof-of-concept trial. TRIAL REGISTRATION: ACTRN12621000641897 (28/5/2021, retrospectively registered).

Influence of X-ray computed tomography (CT) exposure and reconstruction parameters on positron emission tomography (PET) quantitation.

BACKGROUND: The CT of PET CT provides diagnostic information, anatomic localisation and attenuation correction (AC). When only AC is required, very lose dose CT is desirable. CT iterative reconstruction (IR) improves image quality with lower exposures however there is little data on very low dose IR CT for AC of PET. This work assesses the impact of CT exposure and reconstruction algorithm on PET voxel values. METHOD: An anthropomorphic torso phantom was filled with physiologically typical [18]F concentrations in heart, liver and background compartments. A 17-mm-diameter right lung "tumour" filled with [18]F was included (surrounding lung contained no 18[F]). PET was acquired followed by 24 CT acquisitions with varying CT exposures (15-50 mAs, 80-120 kVp, pitch 0.671 or 0.828). Each CT was reconstructed twice using filtered back projection (FBP) or IR and these used for AC of PET. The reference PET reconstruction (RR) used CT acquired at 50 mAs, 120 kVp, pitch 0.828, IR, all others were test PET reconstructions (TR). Regions of interest (ROIs) were drawn in the liver, soft tissue and over "tumour" on each TR and compared with the RR. Voxel values in each TR were compared to the RR using a paired t test and by calculating which and what proportion of voxels in each TR differed by a quantitatively significant difference (QSD) from the RR. RESULTS: TRs reconstructed using lower dose CTs underestimated mean and maximum ROI activity relative to the RR; greater with IR than FBP. Once CT dose index (CTDI) increased to 1 mGy, differences were less than QSD. On voxel analysis, all TRs were significantly different to the RR (p < 0.0001). TRs reconstructed at the lowest CT exposure with IR had 6% of voxels that differed by greater than QSD. Differences were reduced with increasing CTDI and FBP reconstruction. Voxels which exceeded the QSD were spatially localised to regions of high activity, interfaces between different attenuation and areas of CT beam hardening. CONCLUSIONS: Very low dose CT exposures are feasible for accurate PET AC. Scanner- and reconstruction-specific validation should be employed prior very low dose CT AC for PET.

The relative function of damaged kidneys in children does not deteriorate further at 3-year follow-up.

PURPOSE: It is thought that the function of a damaged kidney will deteriorate further with time because of impaired maturation and compensatory hyperfiltration. The aim of this study was to determine changes in relative renal function (RRF) over time in children with vesicoureteric reflux (VUR) and/or urinary tract infection (UTI) where the unilaterally scarred kidney was found to contribute 30% or less to overall function. PATIENTS AND METHODS: Children who met the inclusion criteria and had multiple radionuclide studies during a 12-year period were identified, and RRF was compared. RESULTS: Twenty-seven boys and 3 girls with a median age of 0.8 years (0.08-13.05 years) were included. Eight patients had unilateral VUR, 21 patients had bilateral VUR, and 1 patient had UTIs without VUR. Twenty-one patients underwent reimplantation surgery, and 9 were managed conservatively.At a mean follow-up of 2.64 years (0.26-6.77 years), there was a nonsignificant mean decrease in RRF from 19% (11%-28%) to 18% (9%-29%). The mean change in renal function was not affected by the severity of the initial RRF. CONCLUSIONS: In the medium term, there is no deterioration of RRF of unilaterally severely damaged kidneys associated with either VUR or UTI managed either surgically or conservatively. Boys are at a much greater risk of severe reflux nephropathy.