A Bivalent Inhibitor of Prostate Specific Membrane Antigen Radiolabeled with Copper‐64 with High Tumor Uptake and Retention

Zia, Nicholas; Cullinane, Carleen; Zuylekom, Jessica Van; Waldeck, Kelly; McInnes, Lachlan E.; Buncic, Gojko; Haskali, Mohammad B.; Roselt, Peter; Hicks, Rodney J.; Donnelly, Paul S.

doi:10.1002/anie.201908964

Cited by 36 publications

(61 citation statements)

References 37 publications

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“…In addition, the in uence of renal clearance might also be overcome by using b-emitting isotopes that have a longer half-life, allowing the tumor resection to take place after all renal clearance of non-bound tracer is realized, e.g. using alternative PET isotopes such as 64 Cu (t 1/2 = 12.7 hours), or even theranostic isotopes such as 67 Cu (t 1/2 = 2.5 days), 90 Y (t 1/2 = 2.66 days) or 177 Lu (t 1/2 = 6.6 days) (36,37).…”

Section: Discussionmentioning

confidence: 99%

A DROP-IN beta probe for robot-assisted 68Ga-PSMA radioguided surgery: first ex vivo technology evaluation using prostate cancer specimens

Collamati

OOsterom

Simoni

et al. 2020

Preprint

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Background: Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET-isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET-tracers during robot-assisted tumor-receptor-targeted. In this study, we’ve engineered and validated the performance of a novel DROP-IN beta-particle (DROP-INb) detector.Methods: Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~70 MBq 68Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-INb probe prototype, which merged a scintillating detector with a housing optimized for a 12 mm trocar and prograsp instruments. Results: After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-INb probe prototype was tested in a robotic setting. In the ex vivo setting, the probe – positioned by the robot- was able to identify 68Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located <1 mm below the specimen surface. 68Ga-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-INb probe (S/B>3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta tracing. Conclusions: This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-INb detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.

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Section: Discussionmentioning

confidence: 99%

A DROP-IN beta probe for robot-assisted 68Ga-PSMA radioguided surgery: first ex vivo technology evaluation using prostate cancer specimens

Collamati

OOsterom

Simoni

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, the influence of renal clearance might also be overcome by using β-emitting isotopes that have a longer half-life, allowing the tumor resection to take place after all renal clearance of non-bound tracer is realized, e.g. using alternative PET isotopes such as 64 Cu (t 1/2 = 12.7 hours), or even theranostic isotopes such as 67 Cu (t 1/2 = 2.5 days), 90 Y (t 1/2 = 2.66 days), or 177 Lu (t 1/2 = 6.6 days) [36,37].…”

Section: Discussionmentioning

confidence: 99%

A DROP-IN Beta Probe for Robot-Assisted 68Ga-PSMA Radioguided Surgery: First Ex Vivo Technology Evaluation Using Prostate Cancer Specimens

Collamati

OOsterom

Simoni

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET-isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET-tracers during robot-assisted tumor-receptor-targeted. In this study, we’ve engineered and validated the performance of a novel DROP-IN beta-particle (DROP-INb) detector.Methods: Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~70 MBq 68Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-INb probe prototype, with merged a scintillating detector with a housing optimized for a 12 mm trocar and prograsp instruments. Results: After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-INb probe prototype was tested in a robotic setting. In the ex vivo setting, the probe – positioned by the robot- was able to identify 68Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located <1 mm below the specimen surface. 68Ga-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-INb probe (S/B>3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta tracing. Conclusions: This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-INb detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.

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“…The Donnelly group investigated the bivalent PSMA inhibitor Sar-bisPSMA with the matched pair 64 Cu/ 67 Cu against [ 68 Ga]Ga-PSMA-11 and [ 177 Lu]Lu-PSMA I&T respectively in a LNCaP xenograft model [ 233 , 234 ]. Sar-bisPSMA consists of a sarcophagine based chelator covalently linked to two lysine-ureido-glutamate functional groups, which can be radiolabeled with copper isotopes at room temperature.…”

Section: Potential Radionuclides For the Future Use Of Psma Inhibitorsmentioning

confidence: 99%

Radiolabeled PSMA Inhibitors

Neels

Kopka

Liolios

et al. 2021

Cancers

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PSMA has shown to be a promising target for diagnosis and therapy (theranostics) of prostate cancer. We have reviewed developments in the field of radio- and fluorescence-guided surgery and targeted photodynamic therapy as well as multitargeting PSMA inhibitors also addressing albumin, GRPr and integrin αvβ3. An overview of the regulatory status of PSMA-targeting radiopharmaceuticals in the USA and Europe is also provided. Technical and quality aspects of PSMA-targeting radiopharmaceuticals are described and new emerging radiolabeling strategies are discussed. Furthermore, insights are given into the production, application and potential of alternatives beyond the commonly used radionuclides for radiolabeling PSMA inhibitors. An additional refinement of radiopharmaceuticals is required in order to further improve dose-limiting factors, such as nephrotoxicity and salivary gland uptake during endoradiotherapy. The improvement of patient treatment achieved by the advantageous combination of radionuclide therapy with alternative therapies is also a special focus of this review.

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A Bivalent Inhibitor of Prostate Specific Membrane Antigen Radiolabeled with Copper‐64 with High Tumor Uptake and Retention

Cited by 36 publications

References 37 publications

A DROP-IN beta probe for robot-assisted 68Ga-PSMA radioguided surgery: first ex vivo technology evaluation using prostate cancer specimens

A DROP-IN beta probe for robot-assisted 68Ga-PSMA radioguided surgery: first ex vivo technology evaluation using prostate cancer specimens

A DROP-IN Beta Probe for Robot-Assisted 68Ga-PSMA Radioguided Surgery: First Ex Vivo Technology Evaluation Using Prostate Cancer Specimens

Radiolabeled PSMA Inhibitors

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