The Journal of Nuclear Medicine最新文献

{"title":"Preserved Serotonin Transporter Availability in Parkinson Disease Measured with Either [11C]MADAM or [11C]DASB: A Study Including 2 Separate Cohorts of Nondepressed Patients","authors":"Minyoung Oh, Joachim Brumberg, Vesna Sossi, Andrea Varrone","doi":"10.2967/jnumed.124.268233","DOIUrl":"https://doi.org/10.2967/jnumed.124.268233","url":null,"abstract":"<p>Serotonin transporter (SERT) availability was assessed using 2 tracers, [¹¹C]<em>N</em>,<em>N</em>-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ([¹¹C]DASB) and [¹¹C]<em>N</em>,<em>N</em>-dimethyl-2-(2-amino-4-fluoromethylphenylthio)benzylamine) ([¹¹C]MADAM), in independent cohorts of patients and controls. This study aimed to independently confirm whether SERT remains intact in nondepressed individuals with early-stage Parkinson disease (PD), because the use of diverse methodologies could potentially yield disparate results. <strong>Methods:</strong> Seventeen PD patients (5 women and 12 men; age, 64 ± 7 y; Unified Parkinson’s Disease Rating Scale motor score, 23 ± 5; Beck Depression Inventory score, 5 ± 4) and 20 age- and sex-matched healthy controls underwent [¹¹C]MADAM PET at Karolinska Institutet. Fifteen PD patients (5 women and 10 men; age, 59 ± 9 y; Unified Parkinson’s Disease Rating Scale motor score, 15 ± 7; Beck Depression Inventory score, 4 ± 4) and 8 controls were examined with [¹¹C]DASB PET at the University of British Columbia. PET scans were performed at both institutions using a high-resolution research tomograph. A simplified reference tissue model and Logan graphical analysis were used to calculate the regional nondisplaceable binding potential (BP_ND), using the cerebellum as the reference. Parametric BP_ND images were generated using wavelet-aided parametric imaging. MRI-defined volumes of interest included cortical and subcortical regions, as well as brain stem nuclei. <strong>Results:</strong> There were no significant differences between controls and early-stage PD patients in either the [¹¹C]DASB or the [¹¹C]MADAM cohort, regardless of the analysis method. Group differences (Cohen <em>d</em>) in the [¹¹C]DASB cohort ranged from 0.34 to 0.86 in brain stem nuclei, 0.09 to 0.61 in subcortical regions, and 0.28 to 0.70 in cortical regions. In the [¹¹C]MADAM cohort, they ranged from 0.16 to 0.40, 0.19 to 0.55, and 0.32 to 0.61, respectively. Logan BP_ND highly correlated with simplified reference tissue model BP_ND for both tracers in each group (<em>P</em> &lt; 0.001). <strong>Conclusion:</strong> SERT availability is relatively preserved in nondepressed patients with PD. This study suggests that serotonergic degeneration is not a major feature of the disease in nondepressed patients with nonadvanced disease.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"115 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-in-Human Study of [11C]NCGG401 for Imaging Colony-Stimulating Factor 1 Receptors in the Brain","authors":"Aya Ogata, Hiroshi Ikenuma, Fumihiko Yasuno, Takashi Nihashi, Saori Hattori, Yayoi Sato, Masanori Ichise, Kengo Ito, Takashi Kato, Yasuyuki Kimura","doi":"10.2967/jnumed.124.268699","DOIUrl":"https://doi.org/10.2967/jnumed.124.268699","url":null,"abstract":"<p>Microglia, the immune cells in the brain, play a significant role in the pathophysiology of neurodegenerative diseases. To visualize these cells in the living brain, we developed a PET ligand, [¹¹C]NCGG401 (4-{2-[((1<em>R</em>,2<em>R</em>)-2-hydroxycyclohexyl)(methyl)amino]benzothiazol-6-yloxy}-<em>N</em>-methylpicolinamide, NCGG401), that targets colony-stimulating factor 1 receptor (CSF1R). In this study, we present the first-in-human evaluation of [¹¹C]NCGG401 to assess its safety profile and then to evaluate its kinetics to quantify CSF1R in the human brain. <strong>Methods:</strong> Head to upper thigh PET scans were conducted in 3 healthy men to estimate the effective dose of [¹¹C]NCGG401. Brain PET scans were performed on 6 healthy men, combined with arterial blood sampling and metabolite analyses. Compartmental and graphical models were used to quantify CSF1R in the human brain. [¹¹C]NCGG401 PET data were indirectly compared with regional CSF1R protein levels after death that were reported in a proteomics study. In addition, the results of this study were directly compared with the PET imaging of 18-kDa translocator protein using [¹¹C]DPA-713 (<em>N</em>,<em>N</em>-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide, DPA-713). <strong>Results:</strong> The administration of [¹¹C]NCGG401 did not result in severe adverse events. The effective doses per injected activity were 5.1 ± 0.2 µSv/MBq for men and 6.1 ± 0.3 µSv/MBq for women. [¹¹C]NCGG401 demonstrated good brain permeability, with peak uptake reaching an SUV of 3. Regional total distribution volumes were reliably quantified using the 2-tissue compartment model and a Logan plot with 60 min of scan data. The resulting parametric images reflected the known distribution of CSF1R in the brain. Furthermore, regional total distribution volume values of [¹¹C]NCGG401 showed good correlation with regional CSF1R protein levels. The [¹¹C]NCGG401 images showed regional distributions different from those of [¹¹C]DPA-713. <strong>Conclusion:</strong> [¹¹C]NCGG401 images appear to reflect regional microglia-specific distributions of CSF1R in the brain, consistent with the findings of a CSF1R proteomics study by others. However, ultimate confirmation of specific CSF1R binding should be validated by evaluating, in suitable preclinical or human experiments, pharmacologic blockade of its binding in the brain in vivo.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Trajectory of Dopamine and Serotonin Transporters in Parkinson Disease","authors":"Yujin Song, Jae-Hyeok Lee, Han-Kyeol Kim, Jae Hoon Lee, Young Hoon Ryu, Han Soo Yoo, Chul Hyoung Lyoo","doi":"10.2967/jnumed.124.268365","DOIUrl":"https://doi.org/10.2967/jnumed.124.268365","url":null,"abstract":"<p>Parkinson disease (PD) is a multisystem disorder marked by progressive dopaminergic neuronal degeneration in the substantia nigra, as well as nondopaminergic systems. Our aim was to investigate longitudinal changes in <em>N</em>-(3-[¹⁸F]fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (¹⁸F-FP-CIT) binding at the putamen, substantia nigra, and raphe nuclei in PD. <strong>Methods:</strong> This retrospective cohort study enrolled 127 patients with PD, who underwent ¹⁸F-FP-CIT PET scans twice or more, and 71 age- and sex-matched healthy controls. A temporal trajectory model was created to estimate the longitudinal trajectories of ¹⁸F-FP-CIT PET specific binding ratios (SBRs) of the putamen, substantia nigra, and raphe nuclei from the prodromal to advanced stages. Associations between SBRs and age and motor severity were evaluated. <strong>Results:</strong> At baseline, the PD group showed significantly lower ¹⁸F-FP-CIT SBR of the putamen and substantia nigra and higher ¹⁸F-FP-CIT SBR of the median raphe than did the control group. Longitudinally, ¹⁸F-FP-CIT decline of the putamen and substantia nigra began 11.3 and 3.4 y, respectively, before clinical onset on the more affected side. ¹⁸F-FP-CIT decline of the raphe nuclei remained constant for up to 20 y of disease duration. Topographically, ¹⁸F-FP-CIT SBR of the substantia nigra progressed from the caudal and anterolateral to the rostral and posteromedial regions. <strong>Conclusion:</strong> These results provide in vivo evidence of decreased striatal synaptic dopamine transporter availability approximately 8 y before decreased nigral neuronal dopamine transporter availability, which is strongly correlated with motor deficit. Serotonin transporter availability in the raphe nuclei was elevated in and remained largely unchanged during the disease span.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac Presynaptic Sympathetic Nervous Function Evaluated by Cardiac PET in Patients with Chronotropic Incompetence Without Heart Failure","authors":"Toshihiko Goto, Shohei Kikuchi, Yomei Sakurai, Yoshiro Tsuruta, Kento Mori, Tatsuya Mizoguchi, Yu Kawada, Yasuhiro Shintani, Masashi Yokoi, Sayuri Yamabe, Tsuyoshi Ito, Shuichi Kitada, Hidekatsu Fukuta, Kyoko Matsui, Hitomi Narita, Sumire Nankou, Yoshihiro Seo","doi":"10.2967/jnumed.124.268638","DOIUrl":"https://doi.org/10.2967/jnumed.124.268638","url":null,"abstract":"<p>Chronotropic incompetence (CTI), the inability of the heart to increase its rate with increased activity, leads to exercise intolerance and predicts overall mortality. We previously reported that cardiac β-adrenergic receptor downregulation occurs in patients with CTI without heart failure (HF), indicating postsynaptic sympathetic nervous dysfunction. However, cardiac presynaptic sympathetic nervous system function in CTI is not fully understood. Notably, ¹¹C-hydroxyephedrine PET assesses cardiac presynaptic sympathetic nervous system function. Therefore, we investigated cardiac presynaptic sympathetic nervous system function using cardiac ¹¹C-hydroxyephedrine PET in patients with CTI without HF. <strong>Methods:</strong> We performed cardiac PET in 13 patients with CTI without HF and 9 age-matched healthy controls using ¹¹C-hydroxyephedrine (mean age, 75.1 ± 6.3 y; 59.1% male). The global hydroxyephedrine retention index was determined as myocardial tracer (¹¹C-hydroxyephedrine) activity between 30 and 40 min divided by the activity input integral. CTI was defined as failing to achieve 80% of the heart rate reserve during bicycle ergometer exercise testing. <strong>Results:</strong> The clinical characteristics, including echocardiographic parameters, did not significantly differ between patients with CTI and controls. Peak heart rate was significantly lower in patients with CTI than in controls (107.0 ± 8.2 vs. 138.4 ± 13.6 beats/min, <em>P</em> &lt; 0.001). The global hydroxyephedrine retention index was significantly higher in patients with CTI than in controls (0.14 ± 0.04 vs. 0.10 ± 0.05 min⁻¹, <em>P</em> = 0.046). <strong>Conclusion:</strong> Hydroxyephedrine retention index was significantly higher in patients with CTI without HF than in controls. Our data suggested that impaired norepinephrine release in presynaptic sympathetic nerves contributes to the mechanism of CTI without HF.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vivo Head-to-Head Comparison of [18F]GTP1 with [18F]MK-6240 and [18F]PI-2620 in Alzheimer Disease","authors":"Emily Olafson, Matteo Tonietto, Gregory Klein, Edmond Teng, Andrew W. Stephens, David S. Russell, Karen Pickthorn, Sandra Sanabria Bohorquez","doi":"10.2967/jnumed.124.268623","DOIUrl":"https://doi.org/10.2967/jnumed.124.268623","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.124.268623absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"382 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localized In Vivo Prodrug Activation Using Radionuclides","authors":"Jeremy M. Quintana, Fangchao Jiang, Mikyung Kang, Victor Valladolid Onecha, Arda Könik, Lei Qin, Victoria E. Rodriguez, Huiyu Hu, Nicholas Borges, Ishaan Khurana, Leou I. Banla, Mariane Le Fur, Peter Caravan, Jan Schuemann, Alejandro Bertolet, Ralph Weissleder, Miles A. Miller, Thomas S.C. Ng","doi":"10.2967/jnumed.124.268559","DOIUrl":"https://doi.org/10.2967/jnumed.124.268559","url":null,"abstract":"<p>Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof of principle, we tested whether this strategy of radionuclide-induced drug engagement for release (RAiDER) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing off-target exposure to activated chemotherapy. <b>Methods:</b> We screened the ability of radionuclides to chemically activate a model radiation-activated prodrug consisting of the microtubule-destabilizing monomethyl auristatin E (MMAE) caged by a radiation-responsive phenyl azide, and we interpreted experimental results using the radiobiology computational simulation suite TOPAS-nBio. RAiDER was evaluated in syngeneic mouse models of cancer using the fibroblast activation protein inhibitor (FAPI) agents [^99mTc]Tc-FAPI-34 and [¹⁷⁷Lu]Lu-FAPI-04 and the prostate-specific membrane antigen (PSMA) agent [¹⁷⁷Lu]Lu-PSMA-617, combined with caged MMAE or caged exatecan. Biodistribution in mice, combined with clinical dosimetry, estimated the relationship between radiopharmaceutical uptake in patients and anticipated concentrations of activated prodrug using RAiDER. <b>Results:</b> RAiDER efficiency varied by 70-fold across radionuclides (^99mTc &gt; ¹¹¹In &gt; ¹⁷⁷Lu &gt; ⁶⁴Cu &gt; ³²P &gt; ⁶⁸Ga &gt; ²²³Ra &gt; ¹⁸F), yielding up to 320 nM prodrug activation/Gy of exposure from ^99mTc. Computational simulations implicated low-energy electron&ndash;mediated free radical formation as driving prodrug activation. Radionuclide-activated caged MMAE restored the prodrug&rsquo;s ability to destabilize microtubules and increased its cytotoxicity by up to 2,600-fold that of the nonactivated prodrug. Mice treated with [^99mTc]Tc-FAPI-34 and caged MMAE accumulated concentrations of activated MMAE that were up to 3,000 times greater in tumors than in other tissues. RAiDER with [^99mTc]Tc-FAPI-34 or [¹⁷⁷Lu]Lu-FAPI-04 delayed tumor growth, whereas monotherapies did not (<I>P</I> &lt; 0.003). Clinically guided dosimetry suggests sufficient radiation doses can be delivered to activate therapeutically meaningful levels of prodrug. <b>Conclusion:</b> This proof-of-concept study shows that RAiDER is compatible with multiple radionuclides commonly used in nuclear medicine and can potentially improve the efficacy of radiopharmaceutical therapies to treat cancer safely. RAiDER thus shows promise as an effective strategy to treat disseminated malignancies and broadens the capability of radiopharmaceuticals to trigger diverse biologic and therapeutic responses.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mathematic Modeling of Tumor Growth During [177Lu]Lu-PSMA Therapy: Insights into Treatment Optimization","authors":"Nouran R.R. Zaid, Remco Bastiaannet, Rob Hobbs, George Sgouros","doi":"10.2967/jnumed.124.268457","DOIUrl":"https://doi.org/10.2967/jnumed.124.268457","url":null,"abstract":"<p>The treatment regimen for [¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA) 617 therapy follows that of chemotherapy: 6 administrations of a fixed activity, each separated by 6 wk. Mathematic modeling can be used to test the hypothesis that the current treatment regimen for a radiopharmaceutical modality is suboptimal. <strong>Methods:</strong> A mathematic model was developed to describe tumor growth during [¹⁷⁷Lu]Lu-PSMA therapy. The model examined alternative treatment schedules to maximize tumor mass reduction while still maintaining an acceptable biologically effective dose to kidneys. Median patients’ pharmacokinetics from literature reports were used to obtain the dose rate over time. The model incorporates the Gompertz tumor growth and linear quadratic models to describe the effect of radiation-induced cell kill on tumor growth. For a fixed total activity of 44.4 GBq of [¹⁷⁷Lu]Lu-PSMA-617 and a 6-wk interval between cycles, the efficacy of the standard fractionation (6-cycle) treatment schedule was compared with different treatment regimens for a distribution of published tumor masses. A treatment schedule whereby 7.4 GBq are administered in the first cycle, and the remaining activity (37 GBq) in the second cycle (1-2-cycle treatment), was examined. <strong>Results:</strong> When tumor mass nadir was used as the optimization metric, a lower tumor burden (e.g., &lt;4 g) was insensitive to the number of cycles; the 6-cycle treatment was equivalent to the 1-2-cycle treatment. For larger masses, fewer cycles yielded better results. For a 7-g tumor, the 5-cycle, 4-cycle, 3-cycle and 1-2-cycle schedules were 24%, 50%, 76%, and 84% more efficacious, respectively, than the 6-cycle schedule. The absorbed doses to kidneys, parotid glands, lacrimal glands, and red marrow were 23, 16, 70, and 1 Gy, respectively. In all fractionated schedules, the biologically effective dose to kidneys was within tolerance (&lt;40 Gy). <strong>Conclusion:</strong> On the basis of model-derived simulations, treatment delivered in a 1-2-cycle schedule is recommended to achieve better outcomes for patients undergoing [¹⁷⁷Lu]Lu-PSMA therapy.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Fibroblast Activation Protein for Molecular Imaging of Fibrotic Remodeling in Pulmonary Arterial Hypertension","authors":"Peng Hou, Haiming Chen, Sihao Liang, Wenliang Guo, Ruiyue Zhao, Huailu Pan, Haimin Liu, Youcai Li, Jie Lv, Kaixiang Zhong, Miao Ke, Yimin Fu, Huizhen Zhong, Xinlu Wang, Cheng Hong","doi":"10.2967/jnumed.124.268376","DOIUrl":"https://doi.org/10.2967/jnumed.124.268376","url":null,"abstract":"<p>The purpose of this study was to investigate the feasibility of using ¹⁸F-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in assessing the fibrotic remodeling of the pulmonary artery (PA) and the right ventricle (RV) in pulmonary arterial hypertension (PAH). <strong>Methods:</strong> In a rat model of monocrotaline-induced PAH, rats were euthanized at different time points for tissue analysis (fibroblast activation protein immunofluorescence and Masson’s trichrome staining) after completing ¹⁸F-FAPI PET/CT and hemodynamic measurements. Thirty-eight PAH patients were enrolled to participate in ¹⁸F-FAPI PET/CT imaging, with right heart catheterization and echocardiography performed within 1 wk to assess pulmonary hemodynamics and cardiac function. <strong>Results:</strong> In the animal experiments, RV systolic pressure in monocrotaline rats increased from day 14 to day 21 after injection. ¹⁸F-FAPI uptake and fibroblast activation protein expression in the myocardium and lungs peaked on day 14 after injection. Collagen deposition in the RVs and peripheral PAs of monocrotaline rats progressively deteriorated from day 14 to day 21. In the human PAH study, ¹⁸F-FAPI PET/CT imaging identified varying degrees of ¹⁸F-FAPI uptake in the myocardium and proximal and distal PAs, correlating with clinical, RV function, and pulmonary hemodynamic parameters. Among the 5 follow-up patients who underwent a second ¹⁸F-FAPI PET/CT scan after 6 mo (range, 4–9 mo) of PAH-targeted therapy, 3 demonstrated reduced ¹⁸F-FAPI uptake, corresponding with clinical improvement. <strong>Conclusion:</strong> ¹⁸F-FAPI PET/CT imaging is feasible for visualizing the remodeling of the PA and the RV in PAH. Although it offers promise for assessing disease-related changes, its role in evaluating disease severity and monitoring therapeutic efficacy requires further investigation.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low- and High-Volume Disease in Metastatic Hormone-Sensitive Prostate Cancer: From CHAARTED to PSMA PET—An International Multicenter Retrospective Study","authors":"Lena M. Unterrainer, Thomas A. Hope, Wolfgang P. Fendler, Tristan Grogan, Honest Ndlovu, Wesley Armstrong, Francesco Barbato, Matthias R. Benz, Matthew B. Rettig, Amar U. Kishan, Mike Sathekge, Ken Herrmann, Johannes Czernin, Jeremie Calais","doi":"10.2967/jnumed.124.268441","DOIUrl":"https://doi.org/10.2967/jnumed.124.268441","url":null,"abstract":"<p>High-volume disease (HVD) and low-volume disease (LVD) definitions in metastatic hormone-sensitive prostate cancer (mHSPC) patients are based on conventional imaging (CI) (CT/MRI with bone scan [BS]) according to CHAARTED criteria. HVD and LVD definitions are associated with overall survival and are used for treatment decisions. It remains unknown how these definitions transfer to prostate-specific membrane antigen (PSMA) PET imaging. The aim of this retrospective multicenter study was to compare the CI-based disease volume criteria to PSMA PET–based volume definitions in a CHAARTED-like cohort. <strong>Methods:</strong> mHSPC patients from 5 international sites who underwent PSMA PET/CT or PSMA PET/MRI and BS within a time interval of 100 d and without initiation of a new therapy between the 2 scans were retrospectively included in the analysis. CHAARTED HVD and LVD criteria were applied to BS, CT, MRI, and PSMA PET. HVD was defined by the presence of visceral metastases or at least 4 bone metastases (with ≥1 beyond the spine or pelvis). Whole-body (WB) tumor burden was estimated with the automated bone scan index (aBSI, EXINI v2.0) on BS and with the WB PSMA PET–positive tumor volume (PSMA-TV) on PSMA PET, respectively. <strong>Results:</strong> Sixty-seven patients with paired PSMA PET and BS were included. The median prostate-specific antigen level was 54.9 ng/mL (interquartile range [IQR], 10.4–191.0 ng/mL). On the basis of CI, it was determined that 17 of 67 patients had HVD-CI (25.4%) and 50 of 67 patients had LVD-CI (74.6%). On the basis of PSMA PET, it was determined that 27 of 67 patients had HVD-PET (40.3%) and 24 of 67 patients had LVD-PET (35.8%). In total, 16 of 67 patients (22.4%) had no visible lesion or only locoregional pelvic disease (M0) with PSMA PET (M0-PET). Stage migration between CI and PSMA PET occurred in 27 of 67 patients (40.3%) by both upstaging and downstaging: 11 of 50 (22%) LVD-CI patients were HVD-PET, whereas 1 of 17 (5.9%) HVD-CI and 15 of 50 (30%) of LVD-CI patients were M0-PET. The median WB PSMA-TV and automated BS index were 248.0 mL (IQR, 54.6–1,427.0 mL) and 3.4% (IQR, 1,0–7.2%) for HVD-CI, 25.1 mL (IQR, 6.6–74.6 mL) and 0.1% (IQR, 0.0–0.2%) for LVD-CI, 141.0 mL (IQR, 47.5–458.0 mL) and 0.9% (IQR, 0.04–4.1%) for HVD-PET, and 31.5 mL (IQR, 10.1–67.9 mL) and 0% (IQR, 0–0.1%) for LVD-PET, respectively. The optimal WB PSMA-TV to stratify CI-based CHAARTED LVD-CI versus HVD-CI was 107 mL with a misclassification of 21.9%. <strong>Conclusion:</strong> Compared with CI, addition of PSMA PET leads to M0 downstaging in every third and LVD to HVD upstaging in every fifth mHSPC patient. Future HVD and LVD definitions based on PSMA PET/CT should be adjusted based on patient outcome.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Cardiology Surrogate Biomarkers in Clinical Trials","authors":"Robert J.H. Miller, Krishna K. Patel, Jacek Kwiecinski, Leandro Slipczuk, Marc Dweck, David E. Newby, Panithaya Chareonthaitawee, Piotr Slomka","doi":"10.2967/jnumed.124.267869","DOIUrl":"https://doi.org/10.2967/jnumed.124.267869","url":null,"abstract":"<p>Nuclear cardiology offers a diverse range of imaging tools that provide valuable insights into myocardial perfusion, inflammation, metabolism, neuroregulation, thrombosis, and microcalcification. These techniques are crucial not only for diagnosing and managing cardiovascular conditions but also for gaining pathophysiologic insights. Surrogate biomarkers in nuclear cardiology, represented by detectable imaging changes, correlate with disease processes or therapeutic responses and can serve as endpoints in clinical trials when they demonstrate a clear link with these processes. By providing early indicators of therapeutic efficacy—often before clinical outcomes manifest—surrogate biomarkers can accelerate treatment development. This disease-focused review will highlight key nuclear cardiology surrogate biomarkers, emphasizing the importance of standardized imaging protocols and robust quantitative techniques to ensure accuracy and reproducibility. We will also explore the challenges to the broader adoption of imaging biomarkers, including the need for well-defined pathophysiologic correlations, greater data diversity in clinical research, and overcoming regulatory barriers. Addressing these challenges will improve the utility of imaging biomarkers in clinical trials, enabling more precise cardiovascular care through early diagnosis and therapeutic monitoring, ultimately accelerating the development of novel cardiovascular therapies.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}