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

The field of theranostics dates back over 80 y, when Hertz and Roberts first used radioactive iodine to treat thyroid disease. Recent theranostic approvals for neuroendocrine tumors and prostate cancer have expanded the use of radiopharmaceutical therapy (RPT), and there is significant near-term potential for further expansion across multiple tumor types. This Society of Nuclear Medicine and Molecular Imaging (SNMMI) position paper emphasizes the leadership role of nuclear medicine and nuclear medicine professionals in the high-quality and safe delivery of RPT through specific training, education, regulatory guidance, and collaborations. The rapidly increasing demand for access to and delivery of radiopharmaceuticals has the potential to spur hundreds of thousands of cycles of RPT, with the resultant need for hundreds of new centers and more experts to deliver these therapies. Such an expansion would involve the entire SNMMI membership, including physicians, technologists, radiochemists, physicists, radiopharmacists, scientists, and allied health professionals. All nuclear medicine team members are accredited by specific training programs covering the selection and use of radiopharmaceuticals for theranostics to minimize risks and tailor procedures to the needs of individual patients. The administration of RPT without appropriate training and experience poses significant risks in terms of patient outcomes, impacting safety, efficacy, and overall quality of care. For over 70 y, SNMMI has set comprehensive standards and clinical guidelines for the entire field of nuclear medicine, including RPT, which undergo continual review and updating. Recently, SNMMI established RPT Centers of Excellence and, in collaboration with the International Accreditation Commission (IAC), an accreditation program for facilities administering RPT. Through the Clinical Trials Network (CTN) and Therapy Clinical Trials Network (TCTN), the SNMMI also supports research and quality assurance for imaging cameras used to evaluate patients receiving RPT in clinical trials. Furthermore, collaborations with other international nuclear medicine societies ensure the continual promotion of best practices and knowledge sharing to advance the field of nuclear medicine globally.

Prostate-specific membrane antigen (PSMA) PET/CT has become a common staging modality for newly diagnosed high-risk and unfavorable intermediate-risk prostate cancer after showing improved sensitivity and specificity compared with conventional imaging in clinical trials. We aimed to assess the causal impact of PSMA PET staging on initial treatment selection in real-world practice. Methods: We used observational data from the U.S. Veterans Health Administration to emulate a randomized controlled trial in which patients with newly diagnosed, unfavorable intermediate-, high-, and very-high-risk prostate cancer from January 2022 to December 2023 would have been randomized to undergo either upfront ¹⁸F- or ⁶⁸Ga-PSMA PET staging or conventional imaging (^99mTc bone scan and pelvic CT or MRI). Outcomes of interest included use of frontline androgen deprivation therapy (ADT), second-generation androgen receptor pathway inhibitors (ARPIs), radiotherapy, and radical prostatectomy. Weighted univariable Cox regression was performed to assess the effect of treatment group on each outcome, and 95% CIs were generated from 1,000 bootstrap replicates. Results: In total, 9,049 patients met the criteria for inclusion. PSMA PET staging was associated with higher rates of any ADT use relative to conventional staging (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.19-1.44), higher rates of ARPI use (aHR, 1.52; 95% CI, 1.33-1.78), lower rates of prostatectomy (aHR, 0.69; 95% CI, 0.56-0.83), and no significant effect on the use of radiotherapy (aHR, 1.10; 95% CI, 0.99-1.25). Compared with patients with PSMA stage N0M0, ARPI use was more common in patients with PSMA stage N1M0 (aHR, 6.87; 95% CI, 5.41-8.73) and PSMA stage M1 (aHR, 10.13; 95% CI, 8.16-1.2.58). Patients with PSMA N1M0 disease were much less likely to undergo prostatectomy compared with PSMA N0M0. Conclusion: PSMA PET staging may be leading to fewer prostatectomies and higher use rates of ADT and ARPIs in the Veterans Health Administration.

Cytokines are small proteins that directly regulate immune cell proliferation and signaling. An improved understanding of cytokine expression in specific microenvironments provides critical insights into essential physiologic and pathophysiologic responses to disease and infection. Standard methods used to detect and quantify cytokines are not fully suitable for this purpose, given their limited sensitivity and capacity to address cytokine heterogeneity and short biologic half-lives. In contrast, nuclear imaging modalities (e.g., PET, SPECT) can be used to detect cytokine binding in situ in real time. In this review, we discuss some of the most promising preclinical nuclear imaging agents that have been developed to target specific cytokines. These agents may ultimately be used in the clinical setting to monitor disease progression and responses to treatments for cancer and autoimmune and inflammatory diseases.

Standardized prostate-specific membrane antigen (PSMA) PET/CT evaluation and reporting was introduced to aid interpretation, reproducibility, and communication. Artificial intelligence may enhance these efforts. This study aimed to evaluate the performance of aPROMISE, a deep learning segmentation and reporting software for PSMA PET/CT, compared with a standard image viewer (IntelliSpace Portal [ISP]) in patients undergoing PSMA-radioguided surgery. This allowed the correlation of target lesions with histopathology as a standard of truth. Methods: [⁶⁸Ga]Ga-PSMA-I&T PET/CT of 96 patients with biochemical persistence or recurrence after prostatectomy (median prostate-specific antigen, 0.56 ng/mL; interquartile range, 0.31-1.24 ng/mL), who underwent PSMA-radioguided surgery, were retrospectively analyzed (twice with ISP and twice with aPROMISE) by 2 readers. Cohen κ with 95% CI was calculated to assess intra- and interrater agreement for miTNM stages. Differences between miTNM codelines were classified as no difference, minor difference (change of lymph node region without N/M change), and major difference (miTNM change). Results: Intrarater agreement rates were high for all categories, both readers, and systems (≥91.7%) with moderate to almost perfect κ values (reader 1, ISP, ≥0.51; range, 0.21-0.9; aPROMISE, ≥0.64; range, 0.41-0.99; reader 2, ISP, ≥0.83; range, 0.69-1; aPROMISE, ≥0.78; range, 0.63-1). Major differences occurred more frequently for reader 1 than for reader 2 (ISP, 26% vs. 13.5%; aPROMISE, 22.9% vs. 12.5%). Interrater agreement rates were high with both systems (≥92.2%), demonstrating substantial κ values (ISP, ≥0.73; range, 0.47-0.99; aPROMISE, ≥0.74; range, 0.54-1) with major miTNM staging differences in 21 (21.9%) cases. Readers identified 140 lesions by consensus, of which aPROMISE automatically segmented 129 (92.1%) lesions. Unsegmented lesions either were adjacent to high urine activity or demonstrated low PSMA expression. Agreement rates between imaging and histopathology were substantial (≥86.5%), corresponding to moderate to substantial κ values (≥0.6; range, 0.45-1) with major staging differences in 33 (34.4%) patients. This included 13 (13.5%) cases with metastases distant from targets identified on imaging. One of these lesions was automatically segmented by aPROMISE. Conclusion: Intra- and interreader agreement for PSMA PET/CT evaluation were similarly high with ISP and aPROMISE. The algorithm segmented 92.1% of all identified lesions. Software applications with artificial intelligence could be applied as support tools in PSMA PET/CT evaluation of early prostate cancer.

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.