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Persistent primary hyperparathyroidism is defined as the persistence or recurrence of hypercalcemia within 6 months of parathyroid surgery. Recurrent primary hyperparathyroidism is defined as the recurrence of primary hyperparathyroidism more than 6 months after an initially curative parathyroidectomy. In these situations, it is essential to rule out differential diagnoses, and in particular secondary hyperparathyroidism and familial hypocalciuric hypercalcemia. Failure to remove the pathological parathyroid gland or glands during initial surgery for primary hyperparathyroidism is the most common situation in non-expert centers. In other situations, genetically determined multi-glandular primary hyperparathyroidism must be screened for. More rarely, a second sporadic adenoma is identified, or, exceptionally, a parathyroid carcinoma or parathyromatosis. Effective morphological evaluation, combining a morphological and functional imaging, is essential prior to any new parathyroid surgery. The indications for surgery must be discussed in a multidisciplinary team, assessing the risk/benefit ratio, since the risk of surgical complications is higher. Revision surgery should be performed using a suitable approach, after laryngoscopy, in an expert center, ideally with intraoperative PTH measurement and recurrent nerve neuromonitoring., (Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: The recently released EANM/SNMMI guideline, endorsed by several important clinical and imaging societies in the field of breast cancer (BC) care (ACR, ESSO, ESTRO, EUSOBI/ESR, EUSOMA), emphasized the role of [ 18 F]FDG PET/CT in management of patients with no special type (NST) BC. This review identifies and summarizes similarities, discrepancies and novelties of the EANM/SNMMI guideline compared to NCCN, ESMO and ABC recommendations., Methods: The EANM/SNMMI guideline was based on a systematic literature search and the AGREE tool. The level of evidence was determined according to NICE criteria, and 85 % agreement or higher was reached regarding each statement. Comparisons with NCCN, ESMO and ABC guidelines were examined for specific clinical scenarios in patients with early stage through advanced and metastatic BC., Results: Regarding initial staging of patients with NST BC, [ 18 F]FDG PET/CT is the preferred modality in the EANM-SNMMI guideline, showing superiority as a single modality to a combination of contrast-enhanced CT of thorax-abdomen-pelvis plus bone scan in head-to-head comparisons and a randomized study. Its use is recommended in patients with clinical stage IIB or higher and may be useful in certain stage IIA cases of NST BC. In NCCN, ESMO, and ABC guidelines, [ 18 F]FDG PET/CT is instead recommended as complementary to conventional imaging to solve inconclusive findings, although ESMO and ABC also suggest [ 18 F]FDG PET/CT can replace conventional imaging for staging patients with high-risk and metastatic NST BC. During follow up, NCCN and ESMO only recommend diagnostic imaging if there is suspicion of recurrence. Similarly, EANM-SNMMI states that [ 18 F]FDG PET/CT is useful to detect the site and extent of recurrence only when there is clinical or laboratory suspicion of recurrence, or when conventional imaging methods are equivocal. The EANM-SNMMI guideline is the first to emphasize a role of [ 18 F]FDG PET/CT for assessing early metabolic response to primary systemic therapy, particularly for HER2+ BC and TNBC. In the metastatic setting, EANM-SNMMI state that [ 18 F]FDG PET/CT may help evaluate bone metastases and determine early response to treatment, in agreement with guidelines from ESMO., Conclusions: The recently released EANM/SNMMI guideline reinforces the role of [ 18 F]FDG PET/CT in the management of patients with NST BC supported by extensive evidence of its utility in several clinical scenarios., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Targeted radionuclide therapy with 177 Lu-labelled small conjugates is expanding rapidly, and its success is linked to appropriate patient selection. Companion diagnostic conjugates are usually labelled with 68 Ga, offering good imaging up to ≈2 h post-injection. However, the optimal tumor-to-background ratio is often reached later. This study examined promising positron-emitting radiometals with half-lives between 3 h and 24 h and β + intensity (I β+ ) ≥ 15% and compared them to 68 Ga. The radiometals included: 43 Sc, 44 Sc, 45 Ti, 55 Co, 61 Cu, 64 Cu, 66 Ga, 85m Y, 86 Y, 90 Nb, 132 La, 150 Tb and 152 Tb. 133 La (7.2% I β+ ) was also examined because it was recently discussed, in combination with 132 La, as a possible diagnostic match for 225 Ac., Methods: Total electron and photon doses per decay and per positron; possibly interfering γ-ray emissions; typical activities to be injected for same-day imaging; positron range; and available production routes were examined., Results: For each annihilation process useful for PET imaging, the total energy released (MeV) is: 45 Ti (1.5), 43 Sc (1.6), 61 Cu and 64 Cu (1.8), 68 Ga (1.9), 44 Sc and 133 La (2.9), 55 Co (3.2), 85m Y (3.3), 132 La (4.8), 152 Tb (6.5), 150 Tb (7.1), 90 Nb (8.6), and 86 Y (13.6). Significant amounts (≥ 10%) of ≈0.5 MeV photons that may fall into the acceptance window of PET scanners are emitted by 55 Co, 66 Ga, 85m Y, 86 Y, 132 La, and 152 Tb. Compton background from more energetic photons would be expected for 44 Sc, 55 Co, 66 Ga, 86 Y, 90 Nb, 132 La, 150 Tb, and 152 Tb. The mean positron ranges (mm) of 64 Cu (0.6), 85m Y (1.0), 45 Ti (1.5), 133 La (1.6), 43 Sc and 61 Cu (1.7), 55 Co (2.1), 44 Sc and 86 Y (2.5), and 90 Nb (2.6) were lower than that of 68 Ga (3.6). DOTA chelation is applicable for most of the radiometals, though not ideal for 61 Cu/ 64 Cu. Recent data showed that chelation of 45 Ti with DOTA is feasible. 90 Nb requires different complexing agents (e.g., DFO). Finally, they could be economically produced by proton-induced reactions at medical cyclotrons., Conclusion: In particular, 43 Sc, 45 Ti, and 61 Cu have overall excellent β + decay-characteristics for theranostic applications complementing 177 Lu-labelled small conjugates, and they could be sustainably produced. Like Lu, 43 Sc, 45 Ti and to a lesser extent 61 Cu could be labelled with DOTA., Competing Interests: Declarations. Competing interests: The authors have no conflict of interest to disclose, financial or otherwise., (© 2024. The Author(s).)

Targeting the prostate-specific membrane antigen (PSMA) with radiopharmaceuticals for imaging and/or therapy has demonstrated significant advancement in the management of prostate cancer patients. However, PSMA targeting remains unsuccessful in prostate cancers with low expression of PSMA, which account for 15% of cases. The neurotensin receptor-1 (NTS 1 ) has been highlighted as a suitable oncotarget for imaging and therapy of PSMA-negative prostate cancer lesions. Therefore, heterobivalent probes targeting both PSMA and NTS 1 could improve the prostate cancer management. Herein, we report the development of a branched hybrid probe ( JMV 7489 ) designed to target PSMA and/or NTS 1 bearing relevant pharmacophores and DOTA as the chelating agent. The new ligand was synthesized with a hybrid approach, which includes both syntheses in batch and in the solid phase. Saturation binding experiments were next performed on HT-29 and PC3-PIP cells to derive K d and B max values. On the PC3-PIP cells, [ 68 Ga]Ga- JMV 7489 displayed good affinity towards PSMA ( K d = 53 ± 17 nM; B max = 1393 ± 29 fmol/10 6 cells) in the same range as the corresponding reference monomer. A lower affinity value towards NTS 1 was depicted ( K d = 157 ± 71 nM; B max = 241 ± 42 fmol/10 6 cells on PC3-PIP cells; K d = 246 ± 1 nM; B max = 151 ± 44 fmol/10 6 cells on HT-29 cells) and, surprisingly, it was also the case for the corresponding monomer [ 68 Ga]Ga- JMV 7089 . These results indicate that the DOTA macrocycle and the linker are critical elements to design heterobivalent probes targeting PSMA and NTS 1 with high affinity towards NTS 1 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Early use of targeted radionuclide therapy (TRT) to eradicate disseminated tumor cells (DTCs) might offer cure. Selection of appropriate radionuclides is required. This work highlights the potential of 103 Pd (T 1/2 = 16.991 d) which decays to 103m Rh (T 1/2 = 56.12 min) then to stable 103 Rh with emission of Auger and conversion electrons. Methods: The Monte Carlo track structure code CELLDOSE was used to assess absorbed doses in single cells (14-μm diameter; 10-μm nucleus) and clusters of 19 cells. The radionuclide was distributed on the cell surface, within the cytoplasm, or in the nucleus. Absorbed doses from 103 Pd, 177 Lu and 161 Tb were compared after energy normalization. The impact of non-uniform cell targeting, and the potential benefit from dual-targeting was investigated. Additional results related to 103m Rh, if used directly, are provided. Results: In the single cell, and depending on radionuclide distribution, 103 Pd delivered 7- to 10-fold higher nuclear absorbed dose and 9- to 25-fold higher membrane dose than 177 Lu. In the 19-cell clusters, 103 Pd absorbed doses also largely exceeded 177 Lu. In both situations, 161 Tb stood in-between 103 Pd and 177 Lu. Non-uniform targeting, considering four unlabeled cells within the cluster, resulted in moderate-to-severe dose heterogeneity. For example, with intranuclear 103 Pd, unlabeled cells received only 14% of the expected nuclear dose. Targeting with two 103 Pd-labeled radiopharmaceuticals minimized dose heterogeneity. Conclusion: 103 Pd, a next-generation Auger emitter, can deliver substantially higher absorbed doses than 177 Lu to single tumor cells and cell clusters. This may open new horizons for the use of TRT in adjuvant or neoadjuvant settings, or for targeting minimal residual disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Monte Carlo simulations have been considered for a long time the gold standard for dose calculations in conventional radiotherapy and are currently being applied for the same purpose in innovative radiotherapy techniques such as targeted radionuclide therapy (TRT)., Purpose: We present in this work a benchmarking study of the latest version of the Transport d'Ions Lourds Dans l'Aqua & Vivo (TILDA-V ) Monte Carlo track structure code, highlighting its capabilities for describing the full slowing down of α $\alpha$ -particles in water and the energy deposited in cells by α $\alpha$ -emitters in the context of TRT., Methods: We performed radiation transport simulations of α $\alpha$ -particles (10 keV u - 1 ${\rm u}^{-1}$ -100 MeV u - 1 ${\rm u}^{-1}$ ) in water with TILDA-V and the Particle and Heavy Ion Transport code System (PHITS) version 3.33. We compared the predictions of each code in terms of track parameters (stopping power, range and radial dose profiles) and cellular S-values of the promising radionuclide astatine-211 ( 211 At $^{211}{\rm At}$ ). Additional comparisons were made with available data in the literature., Results: The stopping power, range and radial dose profiles of α $\alpha$ -particles computed with TILDA-V were in excellent agreement with other calculations and available data. Overall, minor differences with PHITS were ascribed to phase effects, that is, related to the use of interaction cross sections computed for water vapor or liquid water. However, important discrepancies were observed in the radial dose profiles of monoenergetic α $\alpha$ -particles, for which PHITS results showed a large underestimation of the absorbed dose compared to other codes and experimental data. The cellular S-values of 211 At $^{211}{\rm At}$ computed with TILDA-V  agreed within 4% with the values predicted by PHITS and MIRDcell., Conclusions: The validation of the TILDA-V code presented in this work opens the possibility to use it as an accurate simulation tool for investigating the interaction of α $\alpha$ -particles in biological media down to the nanometer scale in the context of medical research. The code may help nuclear medicine physicians in their choice of α $\alpha$ -emitters for TRT. Further research will focus on the application of TILDA-V for quantifying radioinduced damage on the deoxyribonucleic acid (DNA) molecule., (© 2024 American Association of Physicists in Medicine.)

The neuropeptide-Y (NPY) family acts through four G protein-coupled receptor subtypes in humans, namely, Y 1 , Y 2 , Y 4 , and Y 5 . A growing body of evidence suggest the involvement of the NPY system in several cancers, notably the Y 5 subtype, thus acting as a relevant target for the development of radiopharmaceuticals for imaging or targeted radionuclide therapy (TRT). Here, the [cPP(1-7),NPY(19-23),Ala 31 ,Aib 32 ,Gln 34 ]hPP scaffold, further referred to as sY 5 ago, was modified with a DOTA chelator and radiolabeled with 68 Ga and 111 In and investigated in vitro and in vivo using the MCF-7 model. For in vivo studies, MCF-7 cells were orthotopically implanted in female nude mice and imaging with small animal positron emission tomography/computed tomography (μPET/CT) was performed. At the end of imaging, the mice were sacrificed. A scrambled version of sY 5 ago, which was also modified with a DOTA chelator, served as a negative control (DOTA-[Nle]sY 5 ago&#95;scrambled). sY 5 ago and DOTA-sY 5 ago showed subnanomolar affinity toward the Y 5 (0.9 ± 0.1 and 0.8 ± 0.1 nM, respectively) and a single binding site at the Y 5 was identified. [ 68 Ga]Ga-DOTA-sY 5 ago and [ 111 In]In-DOTA-sY 5 ago were hydrophilic and showed high specific internalization (1.61 ± 0.75%/10 6 cells at 1 h) and moderate efflux (55% of total binding externalized at 45 min). On μPET/CT images, most of the signal was depicted in the kidneys and the liver. MCF-7 tumors were clearly visualized. On biodistribution studies, [ 68 Ga]Ga-DOTA-sY 5 ago was eliminated by the kidneys (∼60 %ID/g). The kidney uptake is Y 5 -mediated. A specific uptake was also noted in the liver (5.09 ± 1.15 %ID/g vs 1.13 ± 0.21 %ID/g for [ 68 Ga]Ga-DOTA-[Nle]sY 5 ago&#95;scrambled, p < 0.05), the lungs (1.03 ± 0.34 %ID/g vs 0.20 %ID/g, p < 0.05), and the spleen (0.85 ± 0.09%ID/g vs 0.16 ± 0.16%ID/g, p < 0.05). In MCF-7 tumors, [ 68 Ga]Ga-DOTA-sY 5 ago showed 12-fold higher uptake than [ 68 Ga]Ga-DOTA-[Nle]sY 5 ago&#95;scrambled (3.43 ± 2.32 vs 0.27 ± 0.15 %ID/g, respectively, p = 0.0008) at 1 h post-injection. Finally, a proof-of-principle tissular micro-imaging study on a human primary cancer sample showed weak binding of [ 111 In]In-DOTA-sY 5 ago in prostatic intra-neoplasia and high binding in the ISUP1 lesion while normal prostate was free of signal.

Early use of targeted radionuclide therapy to eradicate tumor cell clusters and micrometastases might offer cure. However, there is a need to select appropriate radionuclides and assess the potential impact of heterogeneous targeting. Methods: The Monte Carlo code CELLDOSE was used to assess membrane and nuclear absorbed doses from 177 Lu and 161 Tb (β - -emitter with additional conversion and Auger electrons) in a cluster of 19 cells (14-μm diameter, 10-μm nucleus). The radionuclide distributions considered were cell surface, intracytoplasmic, or intranuclear, with 1,436 MeV released per labeled cell. To model heterogeneous targeting, 4 of the 19 cells were unlabeled, their position being stochastically determined. We simulated situations of single targeting, as well as dual targeting, with the 2 radiopharmaceuticals aiming at different targets. Results: 161 Tb delivered 2- to 6-fold higher absorbed doses to cell membranes and 2- to 3-fold higher nuclear doses than 177 Lu. When all 19 cells were targeted, membrane and nuclear absorbed doses were dependent mainly on radionuclide location. With cell surface location, membrane absorbed doses were substantially higher than nuclear absorbed doses, both with 177 Lu (38-41 vs. 4.7-7.2 Gy) and with 161 Tb (237-244 vs. 9.8-15.1 Gy). However, when 4 cells were not targeted by the cell surface radiopharmaceutical, the membranes of these cells received on average only 9.6% of the 177 Lu absorbed dose and 2.9% of the 161 Tb dose, compared with a cluster with uniform cell targeting, whereas the impact on nuclear absorbed doses was moderate. With an intranuclear radionuclide location, the nuclei of unlabeled cells received only 17% of the 177 Lu absorbed dose and 10.8% of the 161 Tb dose, compared with situations with uniform targeting. With an intracytoplasmic location, nuclear and membrane absorbed doses to unlabeled cells were one half to one quarter those obtained with uniform targeting, both for 177 Lu and for 161 Tb. Dual targeting was beneficial in minimizing absorbed dose heterogeneities. Conclusion: To eradicate tumor cell clusters, 161 Tb may be a better candidate than 177 Lu. Heterogeneous cell targeting can lead to substantial heterogeneities in absorbed doses. Dual targeting was helpful in reducing dose heterogeneity and should be explored in preclinical and clinical studies., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Surgery is the only curative treatment for primary hyperparathyroidism (PHPT). Preoperative imaging is always recommended. 99m Tc-sestamibi scintigraphy is often used in combination with neck ultrasonography as first-line imaging. 99m Tc-sestamibi scintigraphy plays a major role in depicting ectopic parathyroid lesions, as well as in guiding a targeted, minimally invasive parathyroidectomy (MIP). Detecting multiple gland disease (MGD) is important to reduce the risks of surgical failure or unplanned conversion to bilateral surgery. However, the ability to recognize MGD varies greatly depending on the 99m Tc-sestamibi imaging protocol that is used. Dual-tracer 99m Tc-sestamibi/ 123 I highly improves MGD detection compared to single-tracer "dual-phase" 99m Tc-sestamibi imaging. It can thus improve patient selection for MIP. The main requirements for successful dual-tracer imaging are: 1) to acquire 99m Tc-sestamibi and 123-iodine images simultaneously, thus avoiding motion artifacts on subtraction images; to use neck pinhole imaging, in addition to planar imaging, to improve resolution and MGD detection; to follow with dual-tracer SPECT/CT imaging to better define anatomic position of detected parathyroid lesions. If dual-tracer 99m Tc-sestamibi/ 123 I and neck ultrasonography are negative or inconclusive, the second-line imaging in our practice is 18 F-fluorocholine PET/CT. The CT component of 18 F-fluorocholine PET/CT is performed as non-enhanced acquisition plus a contrast-enhanced arterial phase acquisition, to minimize the risk from false-positives due to choline uptake in inflammatory lymph nodes. We use the same strategy of first-line dual-tracer 99m Tc-sestamibi/ 123 I plus neck ultrasonography, followed if necessary by second-line contrast-enhanced 18 F-fluorocholine PET/CT, in patients requiring reoperation for persistent or recurrent PHPT. Additional localization techniques are now rarely necessary.

Introduction: The calculation of resin yttrium-90 ( 90 Y-) microspheres activity for selective internal radiotherapy (SIRT) needs to be investigated., Methods and Materials: Analyses using Simplicit 90 Y (Boston Scientific, Natick, Massachusetts, USA) dosimetry software were performed to determine the concordance between the absorbed doses to the tumor (D T1 and D T2 ) and healthy liver (D N1 and D N2 ) during the pre-treatment and the post-treatment phases. An optimized calculation of the activity of 90 Y-microspheres performed using dosimetry software was applied retrospectively to assess the impact of this calculation method on the treatment., Results: D T1 ranged from 38.8 to 372 Gy, with a mean value of 128.9 ± 73.6 Gy and median of 121.2 Gy [interquartile range (IQR): 81.7-158.8 Gy]. The median D N1 and D N2 was 10.5 Gy (IQR: 5.8-17.6). A significant correlation was between D T1 and D T2 ( r  = 0.88, P  < 0.001) and D N1 and D N2 ( r  = 0.96, P  < 0.001). The optimized activities were calculated; the target dose to the tumor compartment was 120 Gy. No activity reduction was applied in accordance with the tolerance of the healthy liver. Optimization of the microspheres dosages would have resulted in a significant increase in activity for nine treatments (0.21-2.54 GBq) and a reduction for seven others (0.25-0.76 GBq)., Conclusions: The development of customized dosimetry software adapted to clinical practice makes it possible to use dosimetry to optimize the dosage for each patient., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The imaging of Prostate-Specific Membrane Antigen (PSMA) is now widely used at the initial staging of prostate cancers in patients with a high metastatic risk. However, its ability to detect low-grade tumor lesions is not optimal., Methods: First, we prospectively performed neurotensin receptor-1 (NTS 1 ) IHC in a series of patients receiving both [ 68 Ga]Ga-PSMA-617 and [ 68 Ga]Ga-RM2 before prostatectomy. In this series, PSMA and GRP-R IHC were also available (n = 16). Next, we aimed at confirming the PSMA/GRP-R/NTS 1 expression profile by retrospective autoradiography (n = 46) using a specific radiopharmaceuticals study and also aimed to decipher the expression of less-investigated targets such as NTS 2 , SST 2 and CXCR4., Results: In the IHC study, all samples with negative PSMA staining (two patients with ISUP 2 and one with ISUP 3) were strongly positive for NTS 1 staining. No samples were negative for all three stains-for PSMA, GRP-R or NTS 1 . In the autoradiography study, binding of [ 111 In]In-PSMA-617 was high in all ISUP groups. However, some samples did not bind or bound weakly to [ 111 In]In-PSMA-617 (9%). In these cases, binding of [ 111 n]In-JMV 6659 and [ 111 In]In-JMV 7488 towards NTS 1 and NTS 2 was high., Conclusions: Targeting PSMA and NTS 1 /NTS 2 could allow for the detection of all intraprostatic lesions.

Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making. National Comprehensive Cancer Network guidelines recognize prostate-specific membrane antigen (PSMA) PET/CT for use in initial staging of high-risk primary prostate cancer. The gastrin-releasing peptide receptor (GRP-R) is a neuropeptide receptor overexpressed by low-risk prostate cancer cells. We aimed to perform the first (to our knowledge) prospective head-to-head comparison of PSMA- and GRP-R-targeted imaging at initial staging to understand how PSMA PET and GRP-R PET can be used or combined in clinical practice. Methods: This was a prospective, single-center, diagnostic cross-sectional imaging study using anonymized, masked, and independent interpretations of paired PET/CT studies in 22 patients with 68 Ga-PSMA-617 (a radiolabeled PSMA inhibitor) and 68 Ga-RM2 ( 68 Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, a radiolabeled GRP-R antagonist). We enrolled patients with newly diagnosed, biopsy-proven prostate cancer. None had received neoadjuvant hormone therapy or chemotherapy, and all underwent extended pelvic lymph node dissection. Histologic findings served as a reference. Results: On a lesion-based analysis (including lesions < 0.1 cm 3 ), 68 Ga-PSMA-617 PET/CT detected 74.3% (26/35) of all tumor lesions and 68 Ga-RM2 PET/CT detected 78.1% (25/32; 1 patient could not be offered 68 Ga-RM2 PET/CT). Paired examinations showed positive uptake of the 2 tracers in 21 of 32 lesions (65.6%), negative uptake in 5 of 32 lesions (15.6%), and discordant uptake in 6 of 32 lesions (18.8%). Uptake of 68 Ga-PSMA-617 was higher when the International Society of Urological Pathology (ISUP) score was at least 4 versus at least 1 ( P < 0.0001) or 2 ( P  = 0.0002). There were no significant differences in uptake between ISUP scores for 68 Ga-RM2. Median 68 Ga-RM2 SUV max was significantly higher than median 68 Ga-PSMA-617 SUV max in the ISUP-2 subgroup ( P  = 0.01). Conclusion: 68 Ga-PSMA-617 PET/CT is useful to depict higher, more clinically significant ISUP score lesions, and 68 Ga-RM2 PET/CT has a higher detection rate for low-ISUP tumors. Combining PSMA PET and GRP-R PET allows for better classification of intraprostatic lesions., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Neurotensin receptor 2 (NTS 2 ) is a well-known mediator of central opioid-independent analgesia. Seminal studies have highlighted NTS 2 overexpression in a variety of tumors including prostate cancer, pancreas adenocarcinoma, and breast cancer. Herein, we describe the first radiometalated neurotensin analogue targeting NTS 2 . JMV 7488 (DOTA-(βAla) 2 -Lys-Lys-Pro-(D)Trp-Ile-TMSAla-OH) was prepared using solid-phase peptide synthesis, then purified, radiolabeled with 68 Ga and 111 In, and investigated in vitro on HT-29 cells and MCF-7 cells, respectively, and in vivo on HT-29 xenografts. [ 68 Ga]Ga-JMV 7488 and [ 111 In]In-JMV 7488 were quite hydrophilic (logD 7.4 = -3.1 ± 0.2 and -2.7 ± 0.2, respectively, p < 0.0001). Saturation binding studies showed good affinity toward NTS 2 ( K D = 38 ± 17 nM for [ 68 Ga]Ga-JMV 7488 on HT-29 and 36 ± 10 nM on MCF-7 cells; K D = 36 ± 4 nM for [ 111 In]In-JMV 7488 on HT-29 and 46 ± 1 nM on MCF-7 cells) and good selectivity (no NTS 1 binding up to 500 nM). On cell-based evaluation, [ 68 Ga]Ga-JMV 7488 and [ 111 In]In-JMV 7488 showed high and fast NTS 2 -mediated internalization of 24 ± 5 and 25 ± 11% at 1 h for [ 111 In]In-JMV 7488, respectively, along with low NTS 2 -membrane binding (<8%). Efflux was as high as 66 ± 9% at 45 min for [ 68 Ga]Ga-JMV 7488 on HT-29 and increased for [ 111 In]In-JMV 7488 up to 73 ± 16% on HT-29 and 78 ± 9% on MCF-7 cells at 2 h. Maximum intracellular calcium mobilization of JMV 7488 was 91 ± 11% to that of levocabastine, a known NTS 2 agonist on HT-29 cells demonstrating the agonist behavior of JMV 7488. In nude mice bearing HT-29 xenograft, [ 68 Ga]Ga-JMV 7488 showed a moderate but promising significant tumor uptake in biodistribution studies that competes well with other nonmetalated radiotracers targeting NTS 2 . Significant uptake was also depicted in lungs. Interestingly, mice prostate also demonstrated [ 68 Ga]Ga-JMV 7488 uptake although the mechanism was not NTS 2 -mediated., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: Auger emitters exhibit interesting features due to their emission of a cascade of short-range Auger electrons. Maximum DNA breakage efficacy is achieved when decays occur near DNA. Studies of double-strand breaks (DSBs) yields in plasmids revealed cutoff distances from DNA axis of 10.5 Å-12 Å, beyond which the mechanism of DSBs moves from direct to indirect effects, and the yield decreases rapidly. Some authors suggested that the average energy deposited in a DNA cylinder could explain such cutoffs. We aimed to study this hypothesis in further detail., Materials and Methods: Using the Monte Carlo code CELLDOSE, we investigated the influence of the 125 I atom position on energy deposits and absorbed doses per decay not only in a DNA cylinder, but also in individual strands, each modeled as 10 spheres encompassing the fragility sites for phosphodiester bond cleavage., Results: The dose per decay decreased much more rapidly for a sphere in the proximal strand than for the DNA cylinder. For example, when moving the 125 I source from 10.5 Å to 11.5 Å, the average dose to the sphere dropped by 43%, compared to only 13% in the case of the cylinder., Conclusions: Explaining variations in DSBs yields with 125 I position should consider the probability of inducing damage in the proximal strand (nearest to the 125 I atom). The energy received by fragility sites in this strand is highly influenced by the isotropic (4π) emission of 125 I low-energy Auger electrons. The positioning of Auger emitters for targeted radionuclide therapy can be envisioned accordingly.

Background: Minimally invasive parathyroidectomy (MIP) has gained acceptance as the preferred surgical procedure for management of primary hyperparathyroidism (pHPT). Appropriate selection of patients for a MIP is a crucial step in its utilization. The aim of the study was to evaluate the role of 18 F-FCH PET/CT as second-line imaging for accurately directing MIP., Methods: This is a retrospective single-center study. Seventy-two patients with biochemical evidence of pHPT and a non-conclusive or negative first-line imaging (ultrasound and dual isotope subtraction scintigraphy) received 18 F-FCH PET/CT between January 2018 and February 2020. All imaging studies were performed at our institution. Assessment of therapeutic changes and outcomes was performed., Results: of the 72 patients imaged with 18 F-FCH PET/CT, 54 subsequently underwent parathyroidectomy. When considering the ability of 18 F-FCH PET/CT alone to predict a uniglandular disease, the sensitivity, specificity, PPV and NPV were 92.7% (95%CI: 80.1-98.5), 46.2% (19.2-74.9), PPV 87.3% (80.5-92) and NPV 61.2% (31.4-84.5), respectively. When we combined the data provided by 18 F-FCH PET/CT with the data already collected from 1 st line imaging we were able to complete a minimally invasive surgery in 38 of the 41 (92%) patients with a uniglandular disease. Thirteen patients (24%) had a multiglandular disease, all of them except one underwent bilateral neck exploration based on the data collected by all imaging modalities combined. Overall, cure was achieved in 53 (98%) patients., Conclusion: 18 F-FCH PET/CT, interpreted along with first-line imaging results in selected patients, can better facilitate utilization of MIS while maintaining exceptional cure rates., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

During the last two decades, the imaging landscape of multiple myeloma (MM) has evolved with whole-body imaging techniques such as fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET/CT) and MRI replacing X-ray skeletal survey. Both imaging modalities have high diagnostic performance at the initial diagnosis of MM and are key players in the identification of patients needing treatment. Diffusion-weighted MRI has a high sensitivity for bone involvement, while 18 F-FDG PET/CT baseline parameters carry a strong prognostic value. The advent of more efficient therapeutics, such as immunomodulatory drugs and proteasome inhibitors, has called for the use of sensitive imaging techniques for monitoring response to treatment. Diffusion-weighted MRI could improve the specificity of MRI for tumor response evaluation, but questions remain regarding its role as a prognostic factor. Performed at key time points of treatment in newly diagnosed MM patients, 18 F-FDG PET/CT showed a strong association with relapse risk and survival. The deployment of minimal residual disease detection at the cellular or the molecular level may raise questions on the role of these imaging techniques, which will be addressed. This review summarizes and outlines the specificities and respective roles of MRI and 18 F-FDG PET/CT in the management of MM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mesguich, Hulin, Latrabe, Lascaux, Bordenave and Hindié.)

Purpose: Neurotensin receptor-1 (NTS 1 ) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS 1 expression have not been fully clarified., Methods: We studied NTS 1 expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS 1 expression and clinical, pathological, and biological parameters, as well as patient outcomes., Results: Out of 1419 primary breast tumors, moderate to strong positivity for NTS 1 (≥ 10% of tumoral cells stained) was seen in 459 samples (32.4%). NTS 1 staining was cytoplasmic in 304 tumors and nuclear in 155 tumors, a distribution which appeared mutually exclusive. Cytoplasmic overexpression of NTS 1 was present in 21.5% of all breast tumors. In multivariate analysis, factors associated with cytoplasmic overexpression of NTS 1 in breast cancer samples were higher tumor grade, Ki67 ≥ 20%, and higher pT stage. Cytoplasmic NTS 1 was more frequent in tumors other than luminal A (30% versus 17.3%; p < 0.0001). Contrastingly, the main "correlates" of a nuclear location of NTS 1 were estrogen receptor (ER) positivity, low E&E (Elston and Ellis) grade, Ki67 < 20%, and lower pT stage. In NTS 1 -positive samples, cytoplasmic expression of NTS 1 was associated with shorter 10-year metastasis-free interval (p = 0.033) compared to NTS 1 nuclear staining. Ancillary analysis showed NTS 1 expression in 73% of invaded lymph nodes from NTS 1 -positive primaries., Conclusion: NTS 1 overexpression was found in about one-third of breast tumors from patients undergoing primary surgery with two distinct patterns of distribution, cytoplasmic distribution being more frequent in aggressive subtypes. These findings encourage the development of NTS 1 -targeting strategy, including radiopharmaceuticals for imaging and therapy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)