Drug Information
General Information of This Drug
| Drug ID | DRG00048 | |||||
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| Drug Name | Fluorine-18 | |||||
| Synonyms |
Fluorine-18; fluorane; 13981-56-1; 18F radioisotope; fluorine-18 atom; 18 Fluorine; CHEMBL1909275; CHEBI:36939; DTXSID00930616; KRHYYFGTRYWZRS-BJUDXGSMSA-N; F-18; (18)F; (18)9F; Q2031969
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| Target(s) | Human Deoxyribonucleic acid (hDNA) | Target Info | ||||
| Structure |
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| Formula |
FH
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| #Ro5 Violations (Lipinski): 0 | Molecular Weight (mw) | 19.008 | ||||
| Lipid-water partition coefficient (xlogp) | 0.6 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 1 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 1 | |||||
| Rotatable Bond Count (rotbonds) | 0 | |||||
| PubChem CID | ||||||
| Canonical smiles |
F
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| InChI |
InChI=1S/FH/h1H/i1-1
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| InChIKey |
KRHYYFGTRYWZRS-BJUDXGSMSA-N
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| IUPAC Name |
fluorane
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Each Peptide-drug Conjugate Related to This Drug
Full Information of The Activity Data of The PDC(s) Related to This Drug
Piflufolastat F-18 [Investigative]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Specificity | 98% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
252 patients with prostate cancer.
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| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
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| Description |
Within cohort A, the primary end point was the sensitivity and specificity for detection of metastases to the pelvic lymph nodes by 18F-DCFPyL PET/CT. These findings were validated by histopathology after radical proctectomy and lymph node dissection (Figure 6). When all confirmed positive lymph node metastases were considered, the sensitivity of 18F-DCFPyL PET/CT was 40%, with a 98% specificity. It is perhaps unsurprising that histopathology is more sensitivity for the detection of early metastases as a sufficient number of malignant cells must accumulate before any imaging modality will be positive. However, a post-hoc analysis considering only lesions >5 mm found the sensitivity of 18F-DCFPyL PET/CT increased to 60%. Despite this, across all lesions, 18F-DCFPyL PET/CT significantly outperformed conventional CT pelvic imaging with markedly improved specificity (97.7% vs. 65.1%) and positive predictive value (85.1% vs. 28.3%) for pelvic lymph node metastases, as well as sensitivity for disease within the prostate (96.8% vs. 35.9%).
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| Half life period | 8 h | ||||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Sensitivity | 40% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
252 patients with prostate cancer.
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| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
Click to Show/Hide
|
||||
| Description |
Within cohort A, the primary end point was the sensitivity and specificity for detection of metastases to the pelvic lymph nodes by 18F-DCFPyL PET/CT. These findings were validated by histopathology after radical proctectomy and lymph node dissection (Figure 6). When all confirmed positive lymph node metastases were considered, the sensitivity of 18F-DCFPyL PET/CT was 40%, with a 98% specificity. It is perhaps unsurprising that histopathology is more sensitivity for the detection of early metastases as a sufficient number of malignant cells must accumulate before any imaging modality will be positive. However, a post-hoc analysis considering only lesions >5 mm found the sensitivity of 18F-DCFPyL PET/CT increased to 60%. Despite this, across all lesions, 18F-DCFPyL PET/CT significantly outperformed conventional CT pelvic imaging with markedly improved specificity (97.7% vs. 65.1%) and positive predictive value (85.1% vs. 28.3%) for pelvic lymph node metastases, as well as sensitivity for disease within the prostate (96.8% vs. 35.9%).
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| Half life period | 8 h | ||||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Sensitivity | 86% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
208 patients with prostate cancer.
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| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
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|
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| Description |
All patients were dosed with 9 mCi of 18F-DCFPyL and PET/CT images were obtained. 18F-DCFPyL avid lesions were detected in ~60% of the patients. To confirm the metastatic nature of these lesions, biopsies were obtained, if possible. If the lesion was not amendable to biopsy, validation is obtained by focused conventional follow-up imaging or biochemical response to external beam radiotherapy. The differentiation between the number of true metastases validated by other techniques (i.e. true positives, TP) and false positives (FP) allows for the calculation of the correct localization rate (CLR), where the CLR = TP/(TP + FP) * 100 (essentially, PPV with the added requirement of anatomic co-localization). Across all patients, the CLR ranged from 85% to 87% between readers, however the CLR improved as the baseline PSA increased, from 75% to 96% (PSA < 1.0 to PSA ≥ 5.0, respectively). The PPV of the 18F-DCFPyL PET/CT was found to vary by anatomic region and was highest for prostatic lesions (80%) and pelvic lymph nodes (71%), but lower for extrapelvic visceral/soft tissue masses (29%).
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| Half life period | 8 h | ||||
| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Sensitivity | 96% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
93 patients with prostate cancer.
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| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
Click to Show/Hide
|
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| Description |
Within cohort A, the primary end point was the sensitivity and specificity for detection of metastases to the pelvic lymph nodes by 18F-DCFPyL PET/CT. These findings were validated by histopathology after radical proctectomy and lymph node dissection (Figure 6). When all confirmed positive lymph node metastases were considered, the sensitivity of 18F-DCFPyL PET/CT was 40%, with a 98% specificity. It is perhaps unsurprising that histopathology is more sensitivity for the detection of early metastases as a sufficient number of malignant cells must accumulate before any imaging modality will be positive. However, a post-hoc analysis considering only lesions >5 mm found the sensitivity of 18F-DCFPyL PET/CT increased to 60%. Despite this, across all lesions, 18F-DCFPyL PET/CT significantly outperformed conventional CT pelvic imaging with markedly improved specificity (97.7% vs. 65.1%) and positive predictive value (85.1% vs. 28.3%) for pelvic lymph node metastases, as well as sensitivity for disease within the prostate (96.8% vs. 35.9%).
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|
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| Half life period | 8 h | ||||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Negative predictive value | 83.00% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
252 patients with prostate cancer.
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| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
Click to Show/Hide
|
||||
| Description |
Within cohort A, the primary end point was the sensitivity and specificity for detection of metastases to the pelvic lymph nodes by 18F-DCFPyL PET/CT. These findings were validated by histopathology after radical proctectomy and lymph node dissection (Figure 6). When all confirmed positive lymph node metastases were considered, the sensitivity of 18F-DCFPyL PET/CT was 40%, with a 98% specificity. It is perhaps unsurprising that histopathology is more sensitivity for the detection of early metastases as a sufficient number of malignant cells must accumulate before any imaging modality will be positive. However, a post-hoc analysis considering only lesions >5 mm found the sensitivity of 18F-DCFPyL PET/CT increased to 60%. Despite this, across all lesions, 18F-DCFPyL PET/CT significantly outperformed conventional CT pelvic imaging with markedly improved specificity (97.7% vs. 65.1%) and positive predictive value (85.1% vs. 28.3%) for pelvic lymph node metastases, as well as sensitivity for disease within the prostate (96.8% vs. 35.9%).
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| Half life period | 8 h | ||||
| Experiment 6 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Hypertension | 1% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
208 patients with prostate cancer.
|
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| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
Click to Show/Hide
|
||||
| Description |
All patients were dosed with 9 mCi of 18F-DCFPyL and PET/CT images were obtained. 18F-DCFPyL avid lesions were detected in ~60% of the patients. To confirm the metastatic nature of these lesions, biopsies were obtained, if possible. If the lesion was not amendable to biopsy, validation is obtained by focused conventional follow-up imaging or biochemical response to external beam radiotherapy. The differentiation between the number of true metastases validated by other techniques (i.e. true positives, TP) and false positives (FP) allows for the calculation of the correct localization rate (CLR), where the CLR = TP/(TP + FP) * 100 (essentially, PPV with the added requirement of anatomic co-localization). Across all patients, the CLR ranged from 85% to 87% between readers, however the CLR improved as the baseline PSA increased, from 75% to 96% (PSA < 1.0 to PSA ≥ 5.0, respectively). The PPV of the 18F-DCFPyL PET/CT was found to vary by anatomic region and was highest for prostatic lesions (80%) and pelvic lymph nodes (71%), but lower for extrapelvic visceral/soft tissue masses (29%).
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| Half life period | 8 h | ||||
| Experiment 7 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Headache rate | 2% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
345 patients with prostate cancer.
|
||||
| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
Click to Show/Hide
|
||||
| Description |
Within cohort A, the primary end point was the sensitivity and specificity for detection of metastases to the pelvic lymph nodes by 18F-DCFPyL PET/CT. These findings were validated by histopathology after radical proctectomy and lymph node dissection (Figure 6). When all confirmed positive lymph node metastases were considered, the sensitivity of 18F-DCFPyL PET/CT was 40%, with a 98% specificity. It is perhaps unsurprising that histopathology is more sensitivity for the detection of early metastases as a sufficient number of malignant cells must accumulate before any imaging modality will be positive. However, a post-hoc analysis considering only lesions >5 mm found the sensitivity of 18F-DCFPyL PET/CT increased to 60%. Despite this, across all lesions, 18F-DCFPyL PET/CT significantly outperformed conventional CT pelvic imaging with markedly improved specificity (97.7% vs. 65.1%) and positive predictive value (85.1% vs. 28.3%) for pelvic lymph node metastases, as well as sensitivity for disease within the prostate (96.8% vs. 35.9%).
Click to Show/Hide
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| Half life period | 8 h | ||||
| Experiment 8 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Headache rate | 2% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
208 patients with prostate cancer.
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| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
Click to Show/Hide
|
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| Description |
All patients were dosed with 9 mCi of 18F-DCFPyL and PET/CT images were obtained. 18F-DCFPyL avid lesions were detected in ~60% of the patients. To confirm the metastatic nature of these lesions, biopsies were obtained, if possible. If the lesion was not amendable to biopsy, validation is obtained by focused conventional follow-up imaging or biochemical response to external beam radiotherapy. The differentiation between the number of true metastases validated by other techniques (i.e. true positives, TP) and false positives (FP) allows for the calculation of the correct localization rate (CLR), where the CLR = TP/(TP + FP) * 100 (essentially, PPV with the added requirement of anatomic co-localization). Across all patients, the CLR ranged from 85% to 87% between readers, however the CLR improved as the baseline PSA increased, from 75% to 96% (PSA < 1.0 to PSA ≥ 5.0, respectively). The PPV of the 18F-DCFPyL PET/CT was found to vary by anatomic region and was highest for prostatic lesions (80%) and pelvic lymph nodes (71%), but lower for extrapelvic visceral/soft tissue masses (29%).
Click to Show/Hide
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| Half life period | 8 h | ||||
| Experiment 9 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Fatigue | 1% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
345 patients with prostate cancer.
|
||||
| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
Click to Show/Hide
|
||||
| Description |
Within cohort A, the primary end point was the sensitivity and specificity for detection of metastases to the pelvic lymph nodes by 18F-DCFPyL PET/CT. These findings were validated by histopathology after radical proctectomy and lymph node dissection (Figure 6). When all confirmed positive lymph node metastases were considered, the sensitivity of 18F-DCFPyL PET/CT was 40%, with a 98% specificity. It is perhaps unsurprising that histopathology is more sensitivity for the detection of early metastases as a sufficient number of malignant cells must accumulate before any imaging modality will be positive. However, a post-hoc analysis considering only lesions >5 mm found the sensitivity of 18F-DCFPyL PET/CT increased to 60%. Despite this, across all lesions, 18F-DCFPyL PET/CT significantly outperformed conventional CT pelvic imaging with markedly improved specificity (97.7% vs. 65.1%) and positive predictive value (85.1% vs. 28.3%) for pelvic lymph node metastases, as well as sensitivity for disease within the prostate (96.8% vs. 35.9%).
Click to Show/Hide
|
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| Half life period | 8 h | ||||
| Experiment 10 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Fatigue | 1% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
208 patients with prostate cancer.
|
||||
| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
Click to Show/Hide
|
||||
| Description |
All patients were dosed with 9 mCi of 18F-DCFPyL and PET/CT images were obtained. 18F-DCFPyL avid lesions were detected in ~60% of the patients. To confirm the metastatic nature of these lesions, biopsies were obtained, if possible. If the lesion was not amendable to biopsy, validation is obtained by focused conventional follow-up imaging or biochemical response to external beam radiotherapy. The differentiation between the number of true metastases validated by other techniques (i.e. true positives, TP) and false positives (FP) allows for the calculation of the correct localization rate (CLR), where the CLR = TP/(TP + FP) * 100 (essentially, PPV with the added requirement of anatomic co-localization). Across all patients, the CLR ranged from 85% to 87% between readers, however the CLR improved as the baseline PSA increased, from 75% to 96% (PSA < 1.0 to PSA ≥ 5.0, respectively). The PPV of the 18F-DCFPyL PET/CT was found to vary by anatomic region and was highest for prostatic lesions (80%) and pelvic lymph nodes (71%), but lower for extrapelvic visceral/soft tissue masses (29%).
Click to Show/Hide
|
||||
| Half life period | 8 h | ||||
| Experiment 11 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Prostate cancer | ||||
| Efficacy Data | Dysgeusia | 3% | |||
| Evaluation Method | PET/CT | ||||
| Patients Enrolled |
345 patients with prostate cancer.
|
||||
| Administration Dosage | 8-10 mCi | ||||
| MOA of PDC |
PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.
Click to Show/Hide
|
||||
| Description |
Within cohort A, the primary end point was the sensitivity and specificity for detection of metastases to the pelvic lymph nodes by 18F-DCFPyL PET/CT. These findings were validated by histopathology after radical proctectomy and lymph node dissection (Figure 6). When all confirmed positive lymph node metastases were considered, the sensitivity of 18F-DCFPyL PET/CT was 40%, with a 98% specificity. It is perhaps unsurprising that histopathology is more sensitivity for the detection of early metastases as a sufficient number of malignant cells must accumulate before any imaging modality will be positive. However, a post-hoc analysis considering only lesions >5 mm found the sensitivity of 18F-DCFPyL PET/CT increased to 60%. Despite this, across all lesions, 18F-DCFPyL PET/CT significantly outperformed conventional CT pelvic imaging with markedly improved specificity (97.7% vs. 65.1%) and positive predictive value (85.1% vs. 28.3%) for pelvic lymph node metastases, as well as sensitivity for disease within the prostate (96.8% vs. 35.9%).
Click to Show/Hide
|
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| Half life period | 8 h | ||||
[18F]AlF-NOTA-octreotide [Investigative]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Tumor-induced osteomalacia | ||||
| Efficacy Data | Specificity | 100% | |||
| Evaluation Method | 18F-OC PET/CT assay | ||||
| Patients Enrolled |
17 patients with hypophosphatemic osteomalacia suspected to be TIO.
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| Administration Dosage | 3.7 MBq (0.10 mCi) per kilogram of body weight | ||||
| MOA of PDC |
18F-OC PET/CT scan is useful in the detection of tumors causing TIO. Further studies with larger patient populations are needed to validate the result.
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| Description |
The 18F-OC PET/CT scans were positive in 14 patients. Furthermore, 4 of 14 patients were scanned with both 18F-OC and 68Ga-DOTATATE PET/CT. Both studies were able to localize the tumor in all 4 patients. In total, 14 patients had surgery to remove the lesions. Postsurgical pathological examination confirmed causative tumors in these patients, whose symptoms diminished promptly. Serum phosphate levels normalized, confirming the diagnosis of TIO. 18F-OC PET/CT sensitivity, specificity, and accuracy were 87.5%, 100%, and 88.2% respectively. 18F-OC PET/CT findings affected patient management in 88.2% of cases.
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| Experiment 2 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Tumor-induced osteomalacia | ||||
| Efficacy Data | Sensitivity | 87.50% | |||
| Evaluation Method | 18F-OC PET/CT assay | ||||
| Patients Enrolled |
17 patients with hypophosphatemic osteomalacia suspected to be TIO.
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| Administration Dosage | 3.7 MBq (0.10 mCi) per kilogram of body weight | ||||
| MOA of PDC |
18F-OC PET/CT scan is useful in the detection of tumors causing TIO. Further studies with larger patient populations are needed to validate the result.
|
||||
| Description |
The 18F-OC PET/CT scans were positive in 14 patients. Furthermore, 4 of 14 patients were scanned with both 18F-OC and 68Ga-DOTATATE PET/CT. Both studies were able to localize the tumor in all 4 patients. In total, 14 patients had surgery to remove the lesions. Postsurgical pathological examination confirmed causative tumors in these patients, whose symptoms diminished promptly. Serum phosphate levels normalized, confirming the diagnosis of TIO. 18F-OC PET/CT sensitivity, specificity, and accuracy were 87.5%, 100%, and 88.2% respectively. 18F-OC PET/CT findings affected patient management in 88.2% of cases.
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| Experiment 3 Reporting the Activity Data of This PDC | [3] | ||||
| Indication | Neuroendocrine tumour | ||||
| Efficacy Data | Median detection ratio | 91.10% | |||
| Patients Enrolled |
75 patients with histologically confirmed neuroendocrine tumours and routine clinical.
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| MOA of PDC |
18F-AlF-OC is noninferior and even superior to 68Ga-DOTATATE/NOC PET in NET patients. This validates 18F-AlF-OC as an option for clinical practice somatostatin receptor PET.
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| Description |
In total, 4,709 different tumor lesions were detected: 3,454 with 68Ga-DOTATATE/NOC and 4,278 with 18F-AlF-OC. The mean DR with 18F-AlF-OC was significantly higher than with 68Ga-DOTATATE/NOC (91.1% vs. 75.3%; P < 10-5).
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| Experiment 4 Reporting the Activity Data of This PDC | [3] | ||||
| Indication | Neuroendocrine tumour | ||||
| Efficacy Data | Difference in detection ratio | 15.80% | |||
| Patients Enrolled |
75 patients with histologically confirmed neuroendocrine tumours and routine clinical.
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| MOA of PDC |
18F-AlF-OC is noninferior and even superior to 68Ga-DOTATATE/NOC PET in NET patients. This validates 18F-AlF-OC as an option for clinical practice somatostatin receptor PET.
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| Description |
The resulting mean DDR was 15.8%, with a lower margin of the 95% CI (95% CI, 9.6%-22.0%) higher than -15%, which is the prespecified boundary for noninferiority. The mean DDRs for the 68Ga-DOTATATE and 68Ga-DOTANOC subgroups were 11.8% (95% CI, 4.3-19.3) and 27.5% (95% CI, 17.8-37.1), respectively.
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| Experiment 5 Reporting the Activity Data of This PDC | [2] | ||||
| Indication | Tumor-induced osteomalacia | ||||
| Efficacy Data | Accuracy | 88.20% | |||
| Evaluation Method | 18F-OC PET/CT assay | ||||
| Patients Enrolled |
17 patients with hypophosphatemic osteomalacia suspected to be TIO.
|
||||
| Administration Dosage | 3.7 MBq (0.10 mCi) per kilogram of body weight | ||||
| MOA of PDC |
18F-OC PET/CT scan is useful in the detection of tumors causing TIO. Further studies with larger patient populations are needed to validate the result.
|
||||
| Description |
The 18F-OC PET/CT scans were positive in 14 patients. Furthermore, 4 of 14 patients were scanned with both 18F-OC and 68Ga-DOTATATE PET/CT. Both studies were able to localize the tumor in all 4 patients. In total, 14 patients had surgery to remove the lesions. Postsurgical pathological examination confirmed causative tumors in these patients, whose symptoms diminished promptly. Serum phosphate levels normalized, confirming the diagnosis of TIO. 18F-OC PET/CT sensitivity, specificity, and accuracy were 87.5%, 100%, and 88.2% respectively. 18F-OC PET/CT findings affected patient management in 88.2% of cases.
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References