Mp82-10 Psma-Radioguided Surgery: Introducing Molecular Surgery in Patients With Recurrent Prostate Cancer

Maurer, Tobias; Weineisen, Martina; Wester, Hans‐Jürgen; Schottelius, Margret; Okur, Asli; Weirich, Gregor; Kübler, Hubert; Schwaiger, Markus; Gschwend, Jürgen E.; Frisch, B.; Eiber, Matthias

doi:10.1016/j.juro.2015.02.529

Cited by 3 publications

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“…Here, a high in vivo stability represents a major prerequisite. In the clinical setting, RGS is usually performed on the day after tracer injection for practical reasons (35). Its success primarily relies on high lesionto-background contrast at the time of surgery rather than fast tracer kinetics.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation and First Patient Application of^99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer

et al. 2016

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Initial studies in patients have demonstrated the suitability of 111 In-PSMA-I&T ( 111 In-DOTAGA-(3-iodo-y)-f-k-Sub(KuE)) (PSMA is prostatespecific membrane antigen and I&T is imaging and therapy) for radioguided surgery (RGS) of small metastatic prostate cancer (PCa) soft-tissue lesions. To meet the clinical need for a more cost-effective alternative, the PSMA-I&T-based tracer concept was adapted to 99m Tc-labeling chemistry. Two PSMA-I&T-derived inhibitors with all-L-serine-(MAS 3 ) and all-D-serine-(mas 3 ) chelating moieties were evaluated in parallel, and a kit procedure for routine 99m Tc labeling was developed. Methods: PSMA affinities (IC 50 ) and internalization kinetics of 99m Tc-MAS 3 -y-nal-k (Sub-KuE) and 99m Tc-mas 3 -y-nal-k(Sub-KuE) ( 99m Tc-PSMA-I&S for imaging and surgery) were determined using LNCaP cells and ( 125 I-BA) KuE as a radioligand and reference standard. In vivo metabolite analyses and biodistribution studies were performed using CD-1 nu/nu and LNCaP tumor-bearing CB-17 severe combined immunodeficiency mice. The pharmacokinetics of 99m Tc-PSMA-I&S in humans were investigated in a patient with advanced metastatic PCa via sequential planar whole-body SPECT imaging at 1, 3, 5, and 21 h after injection. Additionally, preoperative SPECT/CT (12 h after injection) and 99m Tc-PSMA-I&S-supported RGS (16 h after injection) were performed in 1 PCa patient with proven iliac and inguinal lymph node metastases. Results: A robust and reliable kit-labeling procedure was established, allowing the preparation of 99m Tc-MAS 3 -y-nal-k(Sub-KuE) and 99m Tc-PSMA-I&S in consistently high radiochemical yield and purity ($98%, n . 50 preparations). Because of its improved internalization efficiency and superior in vivo stability, 99m Tc-PSMA-I&S was selected for further in vivo evaluation. Compared with 111 In-PSMA-I&T, 99m Tc-PSMA-I&S showed delayed clearance kinetics but identical uptake in PSMA-positive tissues in the LNCaP xenograft model (1 h after injection). In exemplary PCa patients, a relatively slow whole-body clearance of 99m Tc-PSMA-I&S was observed due to high plasma protein binding (94%) of the tracer. This, however, promoted efficient tracer uptake in PCa lesions over time and led to steadily increasing lesion-to-background ratios up to 21 h after injection. Preoperative SPECT/CT showed a high 99m Tc-PSMA-I&S uptake in all suspect lesions identified in previous 68 Ga-HBED-CC-Ahx-KuE ( 68 Ga-HBED-CC-PSMA) PET/CT, allowing for their successful intraoperative detection and resection during first-in-human RGS. Conclusion: Because of a straightforward and reliable kit production, 99m Tc-PSMA-I&S represents a cost-effective, readily available alternative to 111 In-PSMA-I&T. Initial patient data indicate its comparable or even superior performance as a probe for PSMA-targeted RGS and also hint toward the unexpected potential of 99m Tc-PSMA-I&S as a SPECT imaging agent.

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Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation and First Patient Application of^99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer

et al. 2016

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“…Intravenous injection of 111 In-labeled PSMA-I&T to PCa patients during surgery has enabled the visualization of metastatic lymph nodes, which are normally unobtrusive and unrecognizable (88). Clinically, in patients undergoing salvage lymphadenectomy, the 111 In-PSMA-RGS allows intraoperative detection of small lymph node metastases with high specificity and sensitivity (89).…”

Section: Novel Methods For Intraoperative Tumor Lesion Tracingmentioning

confidence: 99%

Clinical advancement of precision theranostics in prostate cancer

Tan

Fang²,

Tang³

et al. 2023

Front. Oncol.

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Theranostic approaches with positron emission tomography/computed tomography (PET/CT) or PET/magnetic resonance imaging (PET/MRI) molecular imaging probes are being implemented clinically in prostate cancer (PCa) diagnosis and imaging-guided precision surgery. This review article provides a comprehensive summary of the rapidly expanding list of molecular imaging probes in this field, including their applications in early diagnosis of primary prostate lesions; detection of lymph node, skeletal and visceral metastases in biochemical relapsed patients; and intraoperative guidance for tumor margin detection and nerve preservation. Although each imaging probe shows preferred efficacy in some applications and limitations in others, the exploration and research efforts in this field will eventually lead to improved precision theranostics of PCa.

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“…Owing to the high detection rate for lymph node metastases, PSMA-ligand imaging combined with lymphadenectomy and salvage lymph node resection are increasingly used. PSMA-RGS allows the detection of PSMA-positive PCa cells and metastatic lymph nodes during the operation (75). RGS is a radionuclidebased radiomic model to measure intra-operative g-emission using 99m Tc-or 111 In-labeled PSMA-ligand and provide acoustic feedback with a gamma probe (31).…”

Section: Psma Radioguided Surgerymentioning

confidence: 99%

“…111 In-PSMA-I&T-RGS facilitated intra-operative resection of subcentimeter metastatic lymph nodes. The smallest resected metastatic lesion was 2 mm in size (75). In contrast, the 99m Tc, known as the most widely applied and available radioisotope, was introduced as a PSMA-targeted RGS probe due to its mediumenergy g-radiation, low cost, short half-life, and high stability in vivo in 2016 (78).…”

Section: Psma Radioguided Surgerymentioning

confidence: 99%

Current status of PSMA-targeted imaging and therapy

Wang,

Li,

Zhao

et al. 2024

Front. Oncol.

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Currently, the incidence of prostate cancer is increasing, and it has become a great threat to men’s health. The detection, staging, and follow-up of prostate cancer patients are inseparable from morphology or magnetic resonance imaging (MRI). However, these do not fully meet the needs of diagnosis and patient management. In particular, owing to the late diagnosis, metastatic castration-resistant prostate cancer (mCRPC) patients usually have poor survival and few options for further effective treatment. Prostate-specific membrane antigen (PSMA), because of its overexpression on prostate cancer cells, has gained interest due to its application in the imaging and theranostics field. Several PSMA radioligands have been developed for imaging and treating prostate cancer. Many clinical trials have assessed the efficacy and safety profiles of these radionuclide agents and show promise in patients who have exhausted other standard treatment options. To date, several small compounds for targeting PSMA have been developed, and 68Ga-PSMA-11 and 18F-DCFPyL have been approved by the United States (US) Food and Drug Administration (FDA) for imaging of prostate cancer. 111In- or 99mTc-labeled PSMA-ligand can guide surgeons searching for radioactive metastatic lymph nodes, and 177Lu- or 225Ac-labeled PSMA-ligand can be used for internal radiotherapy. Moreover, some molecules for therapeutic application are undergoing different stages of clinical trials. In this review, we present current perspectives on the use of PSMA-targeted imaging and theranostics in prostate cancer. As PSMA-targeted imaging and therapeutics are becoming the standard of care for prostate cancer patients, we emphasize the importance of integrating nuclear medicine physicians into multidisciplinary oncology teams.

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Mp82-10 Psma-Radioguided Surgery: Introducing Molecular Surgery in Patients With Recurrent Prostate Cancer

Cited by 3 publications

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Preclinical Evaluation and First Patient Application of^99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer

Preclinical Evaluation and First Patient Application of^99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer

Clinical advancement of precision theranostics in prostate cancer

Current status of PSMA-targeted imaging and therapy

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Mp82-10 Psma-Radioguided Surgery: Introducing Molecular Surgery in Patients With Recurrent Prostate Cancer

Cited by 3 publications

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Preclinical Evaluation and First Patient Application of99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer

Preclinical Evaluation and First Patient Application of99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer

Clinical advancement of precision theranostics in prostate cancer

Current status of PSMA-targeted imaging and therapy

Contact Info

Product

Resources

About

Preclinical Evaluation and First Patient Application of^99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer

Preclinical Evaluation and First Patient Application of^99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer