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

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Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer. / Robu, Stephanie; Schottelius, Margret; Eiber, Matthias; Maurer, Tobias; Gschwend, Jürgen; Schwaiger, Markus; Wester, Hans-Jürgen.

In: J NUCL MED, Vol. 58, No. 2, 02.2017, p. 235-242.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research

Harvard

Robu, S, Schottelius, M, Eiber, M, Maurer, T, Gschwend, J, Schwaiger, M & Wester, H-J 2017, 'Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer', J NUCL MED, vol. 58, no. 2, pp. 235-242. https://doi.org/10.2967/jnumed.116.178939

APA

Robu, S., Schottelius, M., Eiber, M., Maurer, T., Gschwend, J., Schwaiger, M., & Wester, H-J. (2017). Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer. J NUCL MED, 58(2), 235-242. https://doi.org/10.2967/jnumed.116.178939

Vancouver

Robu S, Schottelius M, Eiber M, Maurer T, Gschwend J, Schwaiger M et al. Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer. J NUCL MED. 2017 Feb;58(2):235-242. https://doi.org/10.2967/jnumed.116.178939

Bibtex

@article{68e71e2902ba4d8ebf11b42335e335ce,
title = "Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer",
abstract = "Initial studies in patients have demonstrated the suitability of 111In-PSMA-I&T (111In-DOTAGA-(3-iodo-y)-f-k-Sub(KuE)) (PSMA is prostate-specific 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 99mTc-labeling chemistry. Two PSMA-I&T-derived inhibitors with all-L-serine- (MAS3) and all-D-serine- (mas3) chelating moieties were evaluated in parallel, and a kit procedure for routine 99mTc labeling was developed.METHODS: PSMA affinities (IC50) and internalization kinetics of 99mTc-MAS3-y-nal-k(Sub-KuE) and 99mTc-mas3-y-nal-k(Sub-KuE) (99mTc-PSMA-I&S for imaging and surgery) were determined using LNCaP cells and (125I-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 99mTc-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 99mTc-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 99mTc-MAS3-y-nal-k(Sub-KuE) and 99mTc-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, 99mTc-PSMA-I&S was selected for further in vivo evaluation. Compared with 111In-PSMA-I&T, 99mTc-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 99mTc-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 99mTc-PSMA-I&S uptake in all suspect lesions identified in previous 68Ga-HBED-CC-Ahx-KuE (68Ga-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, 99mTc-PSMA-I&S represents a cost-effective, readily available alternative to 111In-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 99mTc-PSMA-I&S as a SPECT imaging agent.",
keywords = "Aged, Animals, Antigens, Surface, Glutamate Carboxypeptidase II, Humans, Male, Mice, Mice, SCID, Pilot Projects, Prostatectomy, Prostatic Neoplasms, Radiopharmaceuticals, Surgery, Computer-Assisted, Technetium, Tomography, Emission-Computed, Single-Photon, Treatment Outcome, Case Reports, Journal Article",
author = "Stephanie Robu and Margret Schottelius and Matthias Eiber and Tobias Maurer and J{\"u}rgen Gschwend and Markus Schwaiger and Hans-J{\"u}rgen Wester",
note = "{\textcopyright} 2017 by the Society of Nuclear Medicine and Molecular Imaging.",
year = "2017",
month = feb,
doi = "10.2967/jnumed.116.178939",
language = "English",
volume = "58",
pages = "235--242",
journal = "J NUCL MED",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer

AU - Robu, Stephanie

AU - Schottelius, Margret

AU - Eiber, Matthias

AU - Maurer, Tobias

AU - Gschwend, Jürgen

AU - Schwaiger, Markus

AU - Wester, Hans-Jürgen

N1 - © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

PY - 2017/2

Y1 - 2017/2

N2 - Initial studies in patients have demonstrated the suitability of 111In-PSMA-I&T (111In-DOTAGA-(3-iodo-y)-f-k-Sub(KuE)) (PSMA is prostate-specific 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 99mTc-labeling chemistry. Two PSMA-I&T-derived inhibitors with all-L-serine- (MAS3) and all-D-serine- (mas3) chelating moieties were evaluated in parallel, and a kit procedure for routine 99mTc labeling was developed.METHODS: PSMA affinities (IC50) and internalization kinetics of 99mTc-MAS3-y-nal-k(Sub-KuE) and 99mTc-mas3-y-nal-k(Sub-KuE) (99mTc-PSMA-I&S for imaging and surgery) were determined using LNCaP cells and (125I-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 99mTc-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 99mTc-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 99mTc-MAS3-y-nal-k(Sub-KuE) and 99mTc-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, 99mTc-PSMA-I&S was selected for further in vivo evaluation. Compared with 111In-PSMA-I&T, 99mTc-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 99mTc-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 99mTc-PSMA-I&S uptake in all suspect lesions identified in previous 68Ga-HBED-CC-Ahx-KuE (68Ga-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, 99mTc-PSMA-I&S represents a cost-effective, readily available alternative to 111In-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 99mTc-PSMA-I&S as a SPECT imaging agent.

AB - Initial studies in patients have demonstrated the suitability of 111In-PSMA-I&T (111In-DOTAGA-(3-iodo-y)-f-k-Sub(KuE)) (PSMA is prostate-specific 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 99mTc-labeling chemistry. Two PSMA-I&T-derived inhibitors with all-L-serine- (MAS3) and all-D-serine- (mas3) chelating moieties were evaluated in parallel, and a kit procedure for routine 99mTc labeling was developed.METHODS: PSMA affinities (IC50) and internalization kinetics of 99mTc-MAS3-y-nal-k(Sub-KuE) and 99mTc-mas3-y-nal-k(Sub-KuE) (99mTc-PSMA-I&S for imaging and surgery) were determined using LNCaP cells and (125I-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 99mTc-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 99mTc-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 99mTc-MAS3-y-nal-k(Sub-KuE) and 99mTc-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, 99mTc-PSMA-I&S was selected for further in vivo evaluation. Compared with 111In-PSMA-I&T, 99mTc-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 99mTc-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 99mTc-PSMA-I&S uptake in all suspect lesions identified in previous 68Ga-HBED-CC-Ahx-KuE (68Ga-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, 99mTc-PSMA-I&S represents a cost-effective, readily available alternative to 111In-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 99mTc-PSMA-I&S as a SPECT imaging agent.

KW - Aged

KW - Animals

KW - Antigens, Surface

KW - Glutamate Carboxypeptidase II

KW - Humans

KW - Male

KW - Mice

KW - Mice, SCID

KW - Pilot Projects

KW - Prostatectomy

KW - Prostatic Neoplasms

KW - Radiopharmaceuticals

KW - Surgery, Computer-Assisted

KW - Technetium

KW - Tomography, Emission-Computed, Single-Photon

KW - Treatment Outcome

KW - Case Reports

KW - Journal Article

U2 - 10.2967/jnumed.116.178939

DO - 10.2967/jnumed.116.178939

M3 - SCORING: Journal article

C2 - 27635024

VL - 58

SP - 235

EP - 242

JO - J NUCL MED

JF - J NUCL MED

SN - 0161-5505

IS - 2

ER -