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Background: A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation. Nevertheless, relatively low tumor radiation doses in patients indicate limited stability in humans. We aimed at evaluating the effect of sacubitril, an inhibitor of the neutral endopeptidase 1, on the stability and absorbed doses to tumors and organs by the cholecystokinin-2 receptor agonist [177Lu]Lu-PP-F11N in patients. In this prospective phase 0 study eight consecutive patients with advanced medullary thyroid carcinoma and a current somatostatin receptor subtype 2 PET/CT scan were included. Patients received two short infusions of ~ 1 GBq [177Lu]Lu-PP-F11N in an interval of ~ 4 weeks with and without Entresto® pretreatment in an open-label, randomized cross-over order. Entresto® was given at a single oral dose, containing 48.6 mg sacubitril. Adverse events were graded and quantitative SPECT/CT and blood sampling were performed. Absorbed doses to tumors and relevant organs were calculated. Results: Pretreatment with Entresto® showed no additional toxicity and increased the stability of [177Lu]Lu-PP-FF11N in blood significantly (p < 0.001). Median tumor-absorbed doses were 2.6-fold higher after Entresto® pretreatment (0.74 vs. 0.28 Gy/GBq, P = 0.03). At the same time, an increase of absorbed doses to stomach, kidneys and bone marrow was observed, resulting in a tumor-to-organ absorbed dose ratio not significantly different with and without Entresto®. Conclusions: Premedication with Entresto® results in a relevant stabilization of [177Lu]Lu-PP-FF11N and consecutively increases radiation doses in tumors and organs. Trial registration clinicaltrails.gov, NCT03647657. Registered 20 August 2018. [ABSTRACT FROM AUTHOR]

Molecular imaging, as applied to clinical practice today, is in its early stages. Encouraging advances achieved in clinical positron emission tomography (PET) and small-animal imaging indicate that this technique is evolving into an indispensable diagnostic tool. When employed with complementary morphological imaging procedures, molecular imaging results in substantial diagnostic capability. It will enable the physician to unveil topographic biochemistry in situ and reduce invasive testing. While this is at least in part futuristic, it is clear already today that a comprehensive set of imaging modalities will be required. Imaging modalities most appropriate for molecular imaging are PET, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and ultrasound. The foundation for advances in molecular imaging, however, is not primarily imaging hardware development but scientific advancements in molecular biology and progress in probe development. Other factors to consider are postprocessing software and, inevitably, market dynamics. Thus, it implies efficient collaborations across disciplines, agencies, and industries to develop molecular imaging tools for the clinic. [ABSTRACT FROM AUTHOR]

Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades, it has been known that the cholecystokinin 2 receptor is a promising target for the treatment of MTC with radiolabeled minigastrin analogs. Unfortunately, kidney toxicity has precluded their therapeutic application so far. In 6 consecutive patients, we evaluated with advanced 3-dimensional dosimetry whether improved minigastrin analog 177 Lu-DOTA-(d-Glu) 6 -Ala-Tyr-Gly-Trp-Nle-Asp-PheNH 2 ( 177 Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received 2 injections of about 1 GBq (∼80 μg) of 177 Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random crossover sequence to evaluate biodistribution, pharmacokinetics, and tumor and organ dosimetry. An electrocardiogram was obtained and blood count and blood chemistry were measured up to 12 wk after the administration of 177 Lu-PP-F11N to assess safety. Results: In all patients, 177 Lu-PP-F11N accumulation was visible in tumor tissue, stomach, and kidneys. Altogether, 13 tumors were eligible for dosimetry. The median absorbed doses for tumors, stomach, kidneys, and bone marrow were 0.88 (interquartile range [IQR]: 0.85-1.04), 0.42 (IQR: 0.25-1.01), 0.11 (IQR: 0.07-0.13), and 0.028 (IQR: 0.026-0.034) Gy/GBq, respectively. These doses resulted in median tumor-to-kidney dose ratios of 11.6 (IQR: 8.11-14.4) without SG and 13.0 (IQR: 10.2-18.6) with SG; these values were not significantly different ( P = 1.0). The median tumor-to-stomach dose ratio was 3.34 (IQR: 1.14-4.70). Adverse reactions (mainly hypotension, flushing, and hypokalemia) were self-limiting and not higher than grade 1. Conclusion: Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With a low kidney and bone marrow radiation dose, 177 Lu-PP-F11N shows a promising biodistribution. The dose-limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of 177 Lu-PP-F11N shows a promising biodistribution. The dose-limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of 177 Lu-PP-F11N., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To perform a preliminary evaluation of the image quality of pediatric technetium 99m ((99m)Tc) methylene diphosphonate (MDP) bone single photon emission computed tomography (SPECT) by using iterative reconstruction-ordered subset expectation maximization with three-dimensional resolution recovery (OSEM-3D)-and to assess whether any improvements with use of this technique could lead to a reduction in patient dose or a shortening in imaging time., Materials and Methods: Institutional advisory board approval was obtained for this investigation. Fifty (99m)Tc-MDP SPECT studies of the spine were evaluated (36 female and 14 male patients; mean age, 15.5 years). Each study was acquired by using a dual-detector camera, with each detector rotating 360°. By using filtered back projection (FBP) and OSEM-3D, images were reconstructed from data generated by both detectors. Likewise, OSEM-3D was used to reconstruct data from a single detector simulating half the administered radiopharmaceutical activity. Two nuclear medicine physicians, blinded to the patient data, reviewed the images for image quality in four different categories by using a four-point scale: artifacts (category 1), lesions (category 2), noise (category 3), and image sharpness (category 4)., Results: Compared with FBP, images reconstructed by using OSEM-3D with one or two detectors showed significant improvement in image quality with regard to lesion detection, noise level, and image sharpness (P < .02, .01, and .001, respectively). With OSEM-3D, no significant differences were observed when either one or two detectors were used., Conclusion: Improved image quality of skeletal SPECT with either a 50% reduction in radiation dose or a 50% reduction in acquisition time or combination of the two can be achieved by using OSEM-3D., (© RSNA, 2010.)

Purpose: To compare two methods of reconstructing technetium 99m (99mTc) dimercaptosuccinic acid (DMSA) renal single photon emission computed tomographic (SPECT) data--ordered subset expectation maximization with three-dimensional resolution recovery (OSEM-3D) and filtered back projection (FBP)--in children in terms of improving image quality and reducing the radiopharmaceutical activity and radiation dose., Materials and Methods: The institutional review board approved this retrospective study and waived the requirement for informed patient consent. Fifty sequential pediatric patient 99mTc-DMSA SPECT studies of 98 kidneys were retrospectively analyzed by using a dual-detector gamma camera. FBP reconstruction with data from both detectors was compared with OSEM-3D reconstruction with half the gamma photon counts (ie, data from only one detector). Two nuclear medicine physicians blinded to the patients' medical histories and reconstruction techniques evaluated the studies. Scores for image quality, renal size, and relative function were compared by using paired t tests. Total scores for renal cortical defects were compared by using the Wilcoxon signed rank test. The kappa coefficient was calculated as an indicator of the concordance between the OSEM-3D and FBP reconstruction methods., Results: Image quality was significantly enhanced with OSEM-3D (P < .001, paired t test). Cortical defects were identified better on OSEM-3D images than on FBP images. Of the 98 kidney SPECT studies analyzed, 19 showed identical cortical defects and 75 showed none at both OSEM-3D and FBP. In four kidneys, OSEM-3D depicted cortical defects that were not seen with FBP. No significant difference in relative renal function between the two methods was observed (P = .973)., Conclusion: Compared with FBP, OSEM-3D yielded superior image quality in the evaluation of 99mTc-DMSA renal SPECT data, with the potential for markedly reduced radiation doses and/or shorter scanning times for patients.