Journal of nuclear medicine : official publication, Society of Nuclear Medicine最新文献

As Centiloids are increasingly used in trials and clinical settings to quantify amyloid-β (Aβ) PET, better characterization of sources of measurement error is essential. We examined 2 potential factors driving it: variability in the estimated coefficients in the SUV ratio-to-Centiloid conversion equation related to random sampling of the calibration dataset and PET image resolution. Methods: First, we analyzed [¹¹C]PiB scans in 200 participants with a clinical diagnosis of Alzheimer disease (cAD) and 114 Aβ-negative participants. PET scans were processed using the standard Centiloid pipeline and a nonstandard MRI-based pipeline (native space, cerebellar cortex as reference). We split data into training and test datasets (n = 157 each) to compare conversion equations in subsamples with an n of 10-30 Aβ-negative and 15-50 cAD participants. Second, all [¹¹C]PiB images, along with 604 [¹⁸F]florbetaben and 538 [¹⁸F]florbetapir images, were reduced from high (6/7 mm³) to medium (8 mm³) and low (10 mm³) resolution and resulting Centiloids were compared between resolutions. rPOP and CapAIBL, 2 PET-only processing pipelines, were used to explore the effects of the PET spatial resolution across different pipelines. Results: In the smallest required sample of 15 cAD and 10 Aβ-negative participants, conversion error was 1.7 Centiloids at 25 Centiloids and 3.4 Centiloids at 100 Centiloids. Error decreased to 1.0 Centiloid at 25 Centiloids and 2.0 Centiloids at 100 Centiloids, when including 50 cAD and 30 Aβ-negative participants. Lower image resolution was associated with a systematic difference in Centiloids, especially in highly positive [¹¹C]PiB scans: a scan estimated as 100 Centiloids in high resolution was quantified as 94.2 Centiloids and 84.9 Centiloids at medium and low resolution. When a [¹¹C]PiB scan was quantified as 25 Centiloids in its high resolution, lowering its resolution resulted in reduced values of 23.5 Centiloids and 20.6 Centiloids for medium and low resolution, respectively. Similar trends were observed for [¹⁸F]florbetaben and [¹⁸F]florbetapir scans. Conclusion: A relatively accurate SUV ratio-to-Centiloid conversion equation for level 2 analyses can still be achieved with a minimally required datasets. Increasing the number of cAD participants reduced error at higher values, whereas adding Aβ-negative participants had little effect. Image resolution significantly impacts Centiloids in highly positive scans and should be considered when interpreting data acquired with different settings. Errors remain minimal at 25 Centiloids, the typical cutoff for determining Aβ positivity.

Immune checkpoint inhibitor (ICI) therapy is effective and in routine clinical use for various cancers, but accurately identifying which patients will respond remains a significant challenge. The PET agent ¹⁸F-FDG has uptake by cancer cells as well as inflammation induced by ICI therapy, complicating and often limiting the utility of ¹⁸F-FDG for early response assessment during ICI therapy. An imaging agent that accurately distinguishes responders from nonresponders early in the course of ICI therapy could enable intensification or change of therapy for nonresponders. In this study, the ¹⁸F-labeled amino acid ¹⁸F-MeFAMP, a fluorinated analog selectively targeting system A amino acid transport, was compared with ¹⁸F-FDG in the MC38 syngeneic mouse model of ICI therapy. ¹⁸F-MeFAMP was chosen because of the relatively low uptake of system A substrates in inflammatory tissues combined with growing evidence suggesting system A transporters are involved in immunotherapy. Methods: PET/CT imaging was used to compare tumor uptake of ¹⁸F-MeFAMP with tumor uptake of ¹⁸F-FDG before and 6 d after starting dual ICIs in MC38 tumor-bearing female C57BL/6 mice. SUVs, biologic tumor volumes, and total lesion activity were measured along with selected tumor-to-organ ratios. Histogram analysis of tracer uptake was performed to assess differences in tumor activity distribution between responders and nonresponders. Results: ¹⁸F-FDG showed no significant differences at baseline or after ICI regardless of response. In contrast, ¹⁸F-MeFAMP SUVs defined using a 40% of SUV_max threshold (SUV40%) decreased significantly in responders (-60.0% ± 15.6%, P < 0.0001), whereas nonresponders showed no significant change (+45.5% ± 51.2%, P = 0.09). Similar patterns were observed with SUV_max, biologic tumor volume, and total lesion activity measures with ¹⁸F-MeFAMP. Histogram analysis revealed significant ¹⁸F-MeFAMP uptake differences between groups before and after imaging (P < 0.05). ¹⁸F-MeFAMP demonstrated low uptake in common metastatic sites, including liver, lungs, and brain. Conclusion: ¹⁸F-MeFAMP better detected early ICI response than ¹⁸F-FDG with favorable whole-body imaging properties. These findings support further investigation of ¹⁸F-MeFAMP for early evaluation of response to ICI and the role of system A substrates in cancer and immune cells before and during ICI.

The extravasation of therapeutic radiopharmaceuticals presents a risk of radiation-induced injury. The recent rise in the use of therapeutic radiopharmaceuticals has highlighted the need for a better understanding of the consequences of extravasation and different treatment approaches, which are summarized in this systematic review. Here, we propose a standardized, step-by-step management guide with the aim of integrating this approach into future guidelines. Methods: A search of MEDLINE and Embase databases was conducted. The first search string contained synonyms of extravasation The second search string contained the names of therapeutic radiopharmaceuticals. Case reports on extravasation of therapeutic radiopharmaceuticals were included in the analysis. Extracted data were standardized for nomenclature and absorbed dose units. Reported absorbed doses, side effects, and treatment approaches were grouped by radiopharmaceutical. Proposed management strategies were summarized chronologically by author. Results: After screening 3,033 abstracts, conducting a full-text review of 75 publications, and screening all references of included publications and European Association of Nuclear Medicine guidelines on therapeutic radiopharmaceuticals, 28 publications remained, involving 39 case reports of extravasation of therapeutic radiopharmaceuticals. The severity of side effects varied widely, from mild and quickly resolving to severe, depending on the radiopharmaceutical used. The most frequent acute side effects were transient swelling, pain, and redness. In cases of radiation injury, the degree of severity, ranging from erythema and dry or moist desquamation to necrosis, was related to the absorbed dose. The most frequently reported intervention after extravasation was mobilization of the affected limb, which included massage, elevation of the arm, stress ball use, or hand-pumping exercises. Management strategies to prevent extravasation focused mainly on ensuring adequate vascular access. Conclusion: Extravasation of therapeutic radiopharmaceuticals is a rarely reported complication, with its severity determined by the activity infiltrated, retention time, and energy of the particulate radiation. Severe radiation-induced injuries were observed after radiosynoviorthesis or extravasation of large molecules (e.g., [⁹⁰Y]Y-ibritumomab tiuxetan). To date, there have been no reported cases of radiation-induced damage after extravasation during peptide receptor radionuclide therapy or prostate-specific membrane antigen-targeted radiopharmaceutical therapy. This systematic review highlights the consequences of 39 documented cases of extravasation of therapeutic radiopharmaceuticals and offers a step-by-step management guide.

We developed and evaluated an artificial intelligence (AI)-powered approach for easier quantification of tau PET uptake without requiring structural MR to aid earlier tracking of Alzheimer disease (AD). Methods: We implemented a deep neural network model that normalizes ¹⁸F-AV1451 (tau) PET images to a standard template without requiring MR, using transfer learning from a model pretrained on amyloid PET. This model was integrated into an MR-free pipeline for tau PET quantification and validated on external dataset (Alzheimer Disease Neuroimaging Initiative). We examined correlations between model-derived tau uptake estimates and cognitive measures, including AD stage and episodic memory performance (n = 666). Longitudinal analyses were conducted to assess whether baseline tau deposition predicted future cognitive decline (n = 168). Results: The AI-powered pipeline achieved robust performance with intraclass correlation coefficients exceeding 0.97 for regional uptake estimation compared with MR-based ground truth. We also showed that the tau deposition in metatemporal regions was significantly correlated with Mini-Mental State Examination and Montreal Cognitive Assessment scores. Elevated tau PET uptake in the entorhinal cortex and inferior temporal gyrus predicted future cognitive decline. Conclusion: The proposed AI-powered pipeline enhances the clinical accessibility of tau PET by reducing scan costs and streamlining the uptake quantification, achieving high performance without requiring structural MR. We further demonstrated that the pipeline yields cognitively relevant outcome measures for early diagnosis and monitoring of AD progression to aid more personalized treatment strategies targeting AD biomarkers.

Reactive fibrosis is a complex response to chronic myocardial insults, contributing to heart failure progression. Fibroblast activation protein inhibitor (FAPI) PET shows promise in distinguishing active from established fibrosis. Although antifibrotic therapies may improve left ventricular (LV) function in preclinical studies, their clinical application is limited by the lack of noninvasive imaging methods to assess fibrosis regression. This study investigates the potential of FAPI PET to track the therapeutic transition of activated fibroblast activation protein (FAP)-positive fibroblasts toward a FAP-negative phenotype. Methods: Mice were implanted with minipumps, infused with angiotensin-II/phenylephrine (Ang-II/PE) for 6 wk and scanned with ⁶⁸Ga-FAPI-46 PET/CT longitudinally. Control mice received saline. ⁶⁸Ga-FAPI-46 biodistribution studies were conducted at preselected time points, and FAPI uptake in the major organs was measured ex vivo. To assess the potential reversibility of the FAPI PET signal in the myocardium and liver, Ang-II/PE infusion was discontinued in a group of animals at 1 and 2 wk, respectively. LV structural and functional changes were assessed via echocardiography, tissue fibrosis via histology, and FAP expression via immunohistochemistry. Results: Significant ⁶⁸Ga-FAPI-46 uptake in the myocardium of treated mice peaked at 1 wk. An increase of ⁶⁸Ga-FAPI-46 uptake was also observed in the liver, peaking at 2 wk, and decreased significantly at 4 wk. The PET signal declined to an indiscernible level in the heart and liver early after Ang-II/PE withdrawal. Three weeks after the removal of the minipumps, the hearts of mice previously exposed to Ang-II/PE for 1 wk exhibited a significant reduction in fibrosis compared with mice that were sacrificed immediately after 1 wk of Ang-II/PE infusion, without the 3-wk recovery period. Coinjection with excess unlabeled FAPI-46 reduced uptake in the heart, liver, and kidneys. Despite an increase in LV wall thickness at 1 wk, the ejection fraction remained stable initially but dropped significantly by 4 wk. Conclusion: The rapid decline in PET signal after Ang-II/PE withdrawal shows that FAPI PET effectively visualizes dynamic changes in FAP expression, making it a valuable tool for quickly assessing treatment responses targeting activated fibroblasts. The cardiac FAPI signal precedes functional myocardial changes, indicating that FAPI PET could detect early fibrosis in cardiac remodeling leading to heart failure. FAPI PET may also visualize cardiac cirrhosis, a serious complication of cardiac disorders.