Combined 18F-fluoride and 18F-FDG PET/CT scanning for evaluation of malignancy: results of an international multicenter trial

(18)F-FDG PET/CT is used in a variety of cancers, but because of variable rates of glucose metabolism, not all cancers are reliably identified. (18)F(-) PET/CT allows for the acquisition of highly sensitive and specific images of the skeleton. We prospectively evaluated combined (18)F(-)/(18)F-FDG as a single PET/CT examination for evaluation of cancer patients and compared it with separate (18)F(-) PET/CT and (18)F-FDG PET/CT scans. METHODS: One hundred fifteen participants with cancer were prospectively enrolled in an international multicenter trial evaluating (18)F(-) PET/CT, (18)F-FDG PET/CT, and combined (18)F(-)/(18)F-FDG PET/CT. The 3 PET/CT scans were performed sequentially within 4 wk of one another for each patient. RESULTS: (18)F(-)/(18)F-FDG PET/CT allowed for accurate interpretation of radiotracer uptake outside the skeleton, with findings similar to those of (18)F-FDG PET/CT. In 19 participants, skeletal disease was more extensive on (18)F(-) PET/CT and (18)F(-)/(18)F-FDG PET/CT than on (18)F-FDG PET/CT. In another 29 participants, (18)F(-) PET/CT and (18)F(-)/(18)F-FDG PET/CT showed osseous metastases where (18)F-FDG PET/CT was negative. The extent of skeletal lesions was similar in 18 participants on all 3 scans. CONCLUSION: This trial demonstrated that combined (18)F(-)/(18)F-FDG PET/CT shows promising results when compared with separate (18)F(-) PET/CT and (18)F-FDG PET/CT for evaluation of cancer patients. This result opens the possibility for improved patient care and reduction in health-care costs, as will be further evaluated in future trials

Multimodality approach of perioperative 18F-FDG PET/CT imaging, intraoperative 18F-FDG handheld gamma probe detection, and intraoperative ultrasound for tumor localization and verification of resection of all sites of hypermetabolic activity in a case of occult recurrent metastatic melanoma

<p>Abstract</p> <p>Background</p> <p>The use of diagnostic ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) imaging for the staging, restaging, and treatment monitoring of melanoma patients has become a well-recognized standard of care. It plays a key role in detecting sites of occult disease and is widely utilized in the medical and surgical planning of such patients. In the current report, we describe an innovative multimodality approach of perioperative ¹⁸F-FDG PET/CT imaging, intraoperative ¹⁸F-FDG handheld gamma probe detection, and intraoperative ultrasound for tumor localization and verification of resection of all sites of hypermetabolic tumor foci in a case of occult recurrent metastatic melanoma.</p> <p>Case presentation</p> <p>This report discusses a case of occult recurrent metastatic melanoma, isolated to three separate sites within the subcutaneous tissues of the left thigh region, which was not clinically apparent but was found on diagnostic restaging whole body ¹⁸F-FDG PET/CT scan utilizing an intravenous injection of 14.8 mCi ¹⁸F-FDG. Then, on the day of surgery, the patient received an intravenous injection of 12.8 mCi ¹⁸F-FDG. A multimodality approach of intraoperative handheld gamma probe detection, intraoperative ultrasound tumor localization, specimen PET/CT imaging, and postoperative PET/CT imaging was utilized for accomplishing and verifying the excision of all three sites of occult recurrent metastatic melanoma within the left thigh region.</p> <p>Conclusion</p> <p>This innovative multimodality approach of perioperative ¹⁸F-FDG PET/CT imaging, intraoperative ¹⁸F-FDG handheld gamma probe detection, and intraoperative ultrasound is promising combined technology for aiding in tumor localization and verification of excision and may ultimately impact positively upon long-term outcome of selected patients.</p

Guiding principles on the education and practice of theranostics.

The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists. To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice. Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries. The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics

Combined approach of perioperative 18F-FDG PET/CT imaging and intraoperative 18F-FDG handheld gamma probe detection for tumor localization and verification of complete tumor resection in breast cancer

<p>Abstract</p> <p>Background</p> <p>¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) has become an established method for detecting hypermetabolic sites of known and occult disease and is widely used in oncology surgical planning. Intraoperatively, it is often difficult to localize tumors and verify complete resection of tumors that have been previously detected on diagnostic PET/CT at the time of the original evaluation of the cancer patient. Therefore, we propose an innovative approach for intraoperative tumor localization and verification of complete tumor resection utilizing ¹⁸F-FDG for perioperative PET/CT imaging and intraoperative gamma probe detection.</p> <p>Methods</p> <p>Two breast cancer patients were evaluated. ¹⁸F-FDG was administered and PET/CT was acquired immediately prior to surgery. Intraoperatively, tumors were localized and resected with the assistance of a handheld gamma probe. Resected tumors were scanned with specimen PET/CT prior to pathologic processing. Shortly after the surgical procedure, patients were re-imaged with PET/CT utilizing the same preoperatively administered ¹⁸F-FDG dose.</p> <p>Results</p> <p>One patient had primary carcinoma of breast and a metastatic axillary lymph node. The second patient had a solitary metastatic liver lesion. In both cases, preoperative PET/CT verified these findings and demonstrated no additional suspicious hypermetabolic lesions. Furthermore, intraoperative gamma probe detection, specimen PET/CT, and postoperative PET/CT verified complete resection of the hypermetabolic lesions.</p> <p>Conclusion</p> <p>Immediate preoperative and postoperative PET/CT imaging, utilizing the same ¹⁸F-FDG injection dose, is feasible and image quality is acceptable. Such perioperative PET/CT imaging, along with intraoperative gamma probe detection and specimen PET/CT, can be used to verify complete tumor resection. This innovative approach demonstrates promise for assisting the oncologic surgeon in localizing and verifying resection of ¹⁸F-FDG positive tumors and may ultimately positively impact upon long-term patient outcomes.</p

Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects

Up-regulation of the folding machinery of the heat-shock protein 90 (Hsp90) chaperone protein is crucial for cancer progression. The two Hsp90 isoforms (α and β) play different roles in response to chemotherapy. To identify isoform-selective inhibitors of Hsp90(α/β)/cochaperone p23 interactions, we developed a dual-luciferase (Renilla and Firefly) reporter system for high-throughput screening (HTS) and monitoring the efficacy of Hsp90 inhibitors in cell culture and live mice. HTS of a 30,176 small-molecule chemical library in cell culture identified a compound, N-(5-methylisoxazol-3-yl)-2-[4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidin-2-ylthio]acetamide (CP9), that binds to Hsp90(α/β) and displays characteristics of Hsp90 inhibitors, i.e., degradation of Hsp90 client proteins and inhibition of cell proliferation, glucose metabolism, and thymidine kinase activity, in multiple cancer cell lines. The efficacy of CP9 in disrupting Hsp90(α/β)/p23 interactions and cell proliferation in tumor xenografts was evaluated by non-invasive, repetitive Renilla luciferase and Firefly luciferase imaging, respectively. At 38 h posttreatment (80 mg/kg × 3, i.p.), CP9 led to selective disruption of Hsp90α/p23 as compared with Hsp90β/p23 interactions. Small-animal PET/CT in the same cohort of mice showed that CP9 treatment (43 h) led to a 40% decrease in 18F-fluorodeoxyglucose uptake in tumors relative to carrier control-treated mice. However, CP9 did not lead to significant degradation of Hsp90 client proteins in tumors. We performed a structural activity relationship study with 62 analogs of CP9 and identified A17 as the lead compound that outperformed CP9 in inhibiting Hsp90(α/β)/p23 interactions in cell culture. Our efforts demonstrated the power of coupling of HTS with multimodality molecular imaging and led to identification of Hsp90 inhibitors

European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer

BACKGROUND In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications. OBJECTIVE We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa. DESIGN, SETTING, AND PARTICIPANTS The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores. RESULTS AND LIMITATIONS After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [$^{177}$Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [$^{223}$Ra]RaCl$_{2}$ remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [$^{18F}$]FDG and PSMA PET prior to [$^{177}$Lu]Lu-PSMA therapy. CONCLUSIONS There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community. PATIENT SUMMARY There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide

European Association of Nuclear Medicine Focus 5:Consensus on Molecular Imaging and Theranostics in Prostate Cancer

BACKGROUND: In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.OBJECTIVE: We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa.DESIGN, SETTING, AND PARTICIPANTS: The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores.RESULTS AND LIMITATIONS: After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [177Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [223Ra]RaCl2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [18F]FDG and PSMA PET prior to [177Lu]Lu-PSMA therapy.CONCLUSIONS: There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community.PATIENT SUMMARY: There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.</p

European Association of Nuclear Medicine Focus 5 : Consensus on Molecular Imaging and Theranostics in Prostate Cancer

Funding/Support and role of the sponsor: This research was funded by the EANM and supported by unrestricted grants from Advanced Accelerator Applications—a Novartis company, Monrol, Spectrum Dynamics Medical Ltd., Blue Earth Diagnostics, GE HealthCare, ITM Isotope Technologies Munich SE, Siemens Healthineers, and Telix Pharmaceuticals. These sponsors had no direct or indirect influence on the programme and content of the EANM Focus 5 meeting and the writing or content of this consensus statement. Acknowledgements: We would like to thank Evelyn Mansutti, Susanne Koebe, Andrea Csismazia, Jutta Peter, Petra Neubauer, Andreas Felser, and Henrik Silber (all from EANM) for project management. We also acknowledge all who participated in EANM Focus 5 meeting and especially the patients who participated in clinical and research projects, making it possible to inform expert opinion.Peer reviewe

Evaluation of integrin αvβ6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin αvβ6