Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT.

BACKGROUND: MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate 89Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution. Future implementation of this technique should improve our understanding of MSCTRAIL during its evaluation as a therapy for metastatic lung adenocarcinoma. METHODS: MSCTRAIL were radiolabelled with 89Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of 89Zr-oxine-labelled MSCTRAIL was performed in a mouse model of lung cancer following intravenous injection, and biodistribution was confirmed ex vivo. RESULTS: MSCTRAIL retained the therapeutic efficacy and MSC phenotype in vitro at labelling amounts up to and above those required for clinical imaging. The effect of 89Zr-oxine labelling on cell proliferation rate was amount- and time-dependent. PET-CT imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer up to 1 week post-injection, validated by in vivo bioluminescence imaging, autoradiography, and fluorescence imaging on tissue sections. CONCLUSIONS: 89Zr-oxine labelling and PET-CT imaging present a potential method of evaluating the biodistribution of new cell therapies in patients, including MSCTRAIL. This offers to improve understanding of cell therapies, including mechanism of action, migration dynamics, and inter-patient variability.

Underestimation of 68Ga PET/CT SUV caused by activity overestimation using default calibrator settings.

PURPOSE: A PET/CT scan of a uniformly filled 68Ga phantom resulted in an unexpectedly low SUVmean of 0.88. A potential contributing cause of underestimation of 68Ga SUV is overestimation of 68Ga activity in the Radionuclide Calibrator associated with the PET/CT scanner. To investigate this, a Radionuclide Calibrator cross-calibration exercise was performed. METHODS: A source of 68Ga was measured in 5 Capintec CRC-55tR calibrators using the pre-set 68Ga calibrator factor of 416, and a Veenstra VDC-505 calibrator using a factor recommended by the manufacturer. The source was then measured in an externally located Fidelis Secondary Standard Radionuclide Calibrator. Manual adjustments were made to the Capintec calibrator factors to match the decay corrected Fidelis measurement, followed by a repeat PET/CT scan of a uniform 68Ga phantom. RESULTS: The cross-calibration results showed that the 5 Capintec calibrators systematically overestimated 68Ga activity by 7.8-9.4% (mean 8.5%) compared to the Fidelis. The calibrator factors were adjusted to 456-464 to match the Fidelis measurement, and the repeat phantom scan resulted in a SUVmean of 0.97, within the local tolerance of 1.00 ±â€¯5%. The result for the Veenstra calibrator was within the tolerance of ±5%. CONCLUSIONS: Underestimation of 68Ga SUV was primarily caused by overestimation of 68Ga activity using the pre-set calibrator factor setting on a Capintec CRC-55tR. Improvement in quantification accuracy was achieved by adjusting the 68Ga calibrator factor based upon a cross-calibration exercise. We recommend SUV checks using a uniform phantom and regular calibrator cross-calibration exercises for all isotopes used for quantitative PET/CT imaging.

Does quantification have a role to play in the future of bone SPECT?

Routinely, there is a visual basis to nuclear medicine reporting: a reporter subjectively places a patient's condition into one of multiple discrete classes based on what they see. The addition of a quantitative result, such as a standardised uptake value (SUV), would provide a numerical insight into the nature of uptake, delivering greater objectivity, and perhaps improved patient management.For bone scintigraphy in particular quantification could increase the accuracy of diagnosis by helping to differentiate normal from abnormal uptake. Access to quantitative data might also enhance our ability to characterise lesions, stratify and monitor patients' conditions, and perform reliable dosimetry for radionuclide therapies. But is there enough evidence to suggest that we, as a community, should be making more effort to implement quantitative bone SPECT in routine clinical practice?We carried out multiple queries through the PubMed search engine to facilitate a cross-sectional review of the current status of bone SPECT quantification. Highly cited papers were assessed in more focus to scrutinise their conclusions.An increasing number of authors are reporting findings in terms of metrics such as SUVmax. Although interest in the field in general remains high, the rate of clinical implementation of quantitative bone SPECT remains slow and there is a significant amount of validation required before we get carried away.