The dose-response relationship in a fixed-activity approach generally applied in the treatment of differentiated thyroid cancer is assessed using ¹²⁴I PET/CT. Methods: Pre-therapeutic ¹²⁴I PET/CT images of 47 patients scheduled for radioiodine therapy were retrospectively analyzed. ¹²⁴I PET/CT images were acquired 24 and 96 hours after oral administration of approximately 28 MBq ¹²⁴I-sodium iodide. Lesions were identified as thyroid remnants or metastases (lymph node, lung, bone). After applying a neoteric segmentation technique allowing accurate volume estimation down to the ¹²⁴I PET spatial resolution of 0.15 mL, lesions were divided in a known-volume group and a small-volume group. For the known-volume group, average lesion absorbed dose (AD) values were calculated, whereas for the small-volume group a minimum lesion AD was estimated. Lesion response was determined based on ¹²⁴I PET/CT and ¹³¹I single photon emission computed tomography(/computed tomography) (SPECT/CT) follow-up images. A lesion not detectable on any of the follow-up images was considered a completely responding lesion. Differences in lesion AD estimations between completely and incompletely responding lesions were evaluated by Mann-Whitney U test. Moreover, receiver-operator-characteristics (ROC) curves were used to test the performance of pre-therapeutic ¹²⁴I PET/CT lesion AD for prediction of complete lesion response. Results: In the approach of fixed radioiodine activity (3.0 ± 1.0 GBq), 89% of thyroid remnants and 69% of metastases responded completely. Except for the small-volume groups, the lesion AD of completely responding lesions was significantly higher compared to that of incompletely responding lesions. Using ROC curve analysis, it was shown that for the known-volume group, pre-therapeutic ¹²⁴I PET/CT lesion dosimetry can be used as a prognostic tool to predict lesion-based ¹³¹I therapy response with an area under the curve of 0.76 for remnants and 0.97 for metastases. The corresponding lesion AD threshold value maximizing correct complete response prediction was 90 Gy for remnants and 40 Gy for metastases. Conclusion: In a fixed-activity approach, a statistically significant dose-response relationship for both thyroid remnants and metastases using pre-therapeutic ¹²⁴I PET/CT lesion dosimetry was found. The findings may be useful in patient management.

CD13 is selectively upregulated in angiogenic active endothelium and can serve as a target for molecular imaging tracers to non-invasively visualise angiogenesis in vivo. Non-invasive determination of CD13 expression can potentially be used to monitor treatment response to pro-angiogenic drugs in ischemic heart disease. CD13 binds peptides and proteins through binding to tripeptide asparagine-glycine-arginine (NGR) amino acid residues. Previous studies using in vivo fluorescence microscopy and magnetic resonance imaging indicated that cNGR tripeptide-based tracers specifically bind to CD13 in angiogenic vasculature at the border zone of the infarcted myocardium. In this study, the CD13-binding characteristics of an ¹¹¹In-labelled cyclic NGR peptide (cNGR) were determined. To increase sensitivity, we visualised ¹¹¹In-DTPA-cNGR in combination with ^99mTc-sestamibi using dual-isotope SPECT to localise CD13 expression in perfusion-deficient regions. Myocardial infarction (MI) was induced in Swiss mice by ligation of the left anterior descending coronary artery (LAD). ¹¹¹In-DTPA-cNGR and ^99mTc-sestamibi dual-isotope SPECT imaging was performed 7 days post-ligation in MI mice and in control mice. In addition, ex vivo SPECT imaging on excised hearts was performed, and biodistribution of ¹¹¹In-DTPA-cNGR was determined using gamma counting. Binding specificity of ¹¹¹In-DTPA-cNGR to angiogenic active endothelium was determined using the Matrigel model. Labelling yield of ¹¹¹In-DTPA-cNGR was 95% to 98% and did not require further purification. In vivo, ¹¹¹In-DTPA-cNGR imaging showed a rapid clearance from non-infarcted tissue and a urinary excretion of 82% of the injected dose (I.D.) 2 h after intravenous injection in the MI mice. Specific binding of ¹¹¹In-DTPA-cNGR was confirmed in the Matrigel model and, moreover, binding was demonstrated in the infarcted myocardium and infarct border zone. Our newly designed and developed angiogenesis imaging probe ¹¹¹In-DTPA-cNGR allows simultaneous imaging of CD13 expression and perfusion in the infarcted myocardium and the infarct border zone by dual-isotope micro-SPECT imaging.

Background: Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: ^99mTc, ¹¹¹In, ¹²³I, ¹²⁴I, ¹³¹I, ¹⁷⁷Lu, and ⁹⁰Y. Methods: In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested. For each radionuclide, a set of four samples comprising two clinical containers (10-mL glass vial and 3-mL syringe) with two filling volumes were measured. The reference value of each sample was determined by two certified radioactivity calibration centers (SCK CEN and JRC) using two secondary standard ionization chambers. The deviation in measured activity with respect to the reference value was determined for each radionuclide and each measurement geometry. In addition, the combined systematic deviation of activity measurements in a theragnostic setting was evaluated for 5 clinically relevant theragnostic pairs: ¹³¹I/¹²³I, ¹³¹I/¹²⁴I, ¹⁷⁷Lu/¹¹¹In, ⁹⁰Y/^99mTc, and ⁹⁰Y/¹¹¹In. Results: For ^99mTc, ¹³¹I, and ¹⁷⁷Lu, a small minority of measurements were not within ± 5% range from the reference activity (percentage of measurements not within range: ^99mTc, 6%; ¹³¹I, 14%; ¹⁷⁷Lu, 24%) and almost none were outside ± 10% range. However, for ¹¹¹In, ¹²³I, ¹²⁴I, and ⁹⁰Y, more than half of all measurements were not accurate within ± 5% range (¹¹¹In, 51%; ¹²³I, 83%; ¹²⁴I, 63%; ⁹⁰Y, 61%) and not all were within ± 10% margin (¹¹¹In, 22%; ¹²³I, 35%; ¹²⁴I, 15%; ⁹⁰Y, 25%). A large variability in measurement accuracy was observed between radionuclide calibrator systems, type of sample container (vial vs syringe), and source-geometry calibration/correction settings used. Consequently, we observed large combined deviations (percentage deviation > ± 10%) for the investigated theragnostic pairs, in particular for ⁹⁰Y/¹¹¹In, ¹³¹I/¹²³I, and ⁹⁰Y/^99mTc. Conclusions: Our study shows that substantial over- or underestimation of therapeutic patient doses is likely to occur in a theragnostic setting due to errors in the assessment of radioactivity with radionuclide calibrators. These findings underline the importance of thorough validation of radionuclide calibrator systems for each clinically relevant radionuclide and sample geometry.

Gallium-68 (⁶⁸Ga) is characterized by relatively high positron energy compared to Fluorine-18 (¹⁸F), causing substantial image quality degradation. Furthermore, the presence of statistical noise can further degrade image quality. The aim of this literature review is to identify the recently developed positron range correction techniques for ⁶⁸Ga, as well as noise reduction methods to enhance the image quality of low count ⁶⁸Ga PET imaging. The search engines PubMed and Scopus were employed, and we limited our research to published results from January 2010 until 1 August 2022. Positron range correction was achieved by using either deblurring or deep learning approaches. The proposed techniques improved the image quality and, in some cases, achieved an image quality comparable to ¹⁸F PET. However, none of these techniques was validated in clinical studies. PET denoising for ⁶⁸Ga-labeled radiotracers was reported using either reconstruction-based techniques or deep learning approaches. It was demonstrated that both approaches can substantially enhance the image quality by reducing the noise levels of low count ⁶⁸Ga PET imaging. The combination of ⁶⁸Ga-specific positron range correction techniques and image denoising approaches may enable the application of low-count, high-quality ⁶⁸Ga PET imaging in a clinical setting.

Posterior lumbar interbody fusion (PLIF) is a method that allows decompression of the spinal canal and nerve roots by laminectomy combined with fusion by means of intervertebral cages filled with bone graft and pedicle screw fixation. Conventional imaging techniques, such as plain radiography and computed tomography (CT), have limitations to assess bony fusion dynamics.