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Pilot study of 68Ga-DOTA-F(ab')2-trastuzumab in patients with breast cancer.

Beylergil V, Morris PG, Smith-Jones PM, Modi S, Solit D, Hudis CA, Lu Y, O'Donoghue J, Lyashchenko SK, Carrasquillo JA, Larson SM, Akhurst TJ - Nucl Med Commun (2013)

Bottom Line: The one patient who did not receive 68Ga-DOTA-F(ab')2-trastuzumab was excluded from analysis.It was determined that 68Ga-DOTA-F(ab')2-trastuzumab was well tolerated, with a T½ of ≈ 3.6 ± 0.9 h; the critical organ was the kidney, with a mean dose of 0.383 cGy/37 MBq; and tumor targeting was seen in 4/8 patients with HER2-positive disease.The reagent is safe, and assessments through additional studies in a better-defined group of patients, using larger administered masses of antibodies, with a better immunoreactive fraction are needed.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Radiology, Molecular Imaging and Therapy Service bDepartment of Medicine, Breast Cancer Medicine Service cHuman Oncology and Pathogenesis Program dDepartment of Medical Physics eRadiochemistry and Molecular Imaging Probes Core Facility, Memorial Sloan-Kettering Cancer Center Departments of fRadiology gMedicine, Weill Cornell Medical College, New York, New York, USA.

ABSTRACT

Objective: 68Ga-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-F(ab')2-trastuzumab [68Ga-DOTA-F(ab')2-trastuzumab] has been developed at our institution as a positron imaging reagent for assessing human epidermal growth factor receptor 2 (HER2) expression status by in-vivo imaging. Initial studies on animals demonstrated promising results in the monitoring of treatment response to heat shock protein 90-targeted drugs that inhibit the client protein HER2. We report here our initial clinical experience in the assessment of the toxicity, pharmacokinetics, biodistribution, and dosimetry profile of 68Ga-DOTA-F(ab')2-trastuzumab with PET/computed tomography using a mean of 236 MBq/5 mg administered intravenously.

Materials and methods: A group of 16 women with breast cancer were enrolled in this study. The one patient who did not receive 68Ga-DOTA-F(ab')2-trastuzumab was excluded from analysis. Both HER2-negative (n=7) and HER2-positive (n=8) cases were studied. Among the latter, seven had undergone trastuzumab treatment previously and one had not.

Results: It was determined that 68Ga-DOTA-F(ab')2-trastuzumab was well tolerated, with a T½ of ≈ 3.6 ± 0.9 h; the critical organ was the kidney, with a mean dose of 0.383 cGy/37 MBq; and tumor targeting was seen in 4/8 patients with HER2-positive disease.

Conclusion: The reagent is safe, and assessments through additional studies in a better-defined group of patients, using larger administered masses of antibodies, with a better immunoreactive fraction are needed.

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Related in: MedlinePlus

Lytic lesion in the left calvarium with 68Ga-DOTA-F(ab′)2-trastuzumab uptake (patient 1). 68Ga-DOTA-F(ab′)2-trastuzumab, 68Ga-1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-F(ab′)2-trastuzumab.
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Figure 4: Lytic lesion in the left calvarium with 68Ga-DOTA-F(ab′)2-trastuzumab uptake (patient 1). 68Ga-DOTA-F(ab′)2-trastuzumab, 68Ga-1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-F(ab′)2-trastuzumab.

Mentions: The visual analysis of the lesions is given in Table 1. In all, seven of 15 (47%) patients had HER2-negative breast cancer on histological analysis and did not show any tumor localization of 68Ga (Table 1). Eight (53%) patients were HER2 positive and three among them had ongoing therapy with trastuzumab at the time of scanning. One of the patients with HER2-positive breast cancer was trastuzumab naive, whereas all others had received prior treatment. All patients with HER2-positive disease had undergone recent 18F-FDG scans and all had 18F-FDG-avid disease. All seven patients with HER2-negative breast cancer also had 18F-FDG-positive disease. Only seven 18F-FDG-avid lesions showed appreciable 68Ga-DOTA-F(ab′)2-trastuzumab uptake in a total of four patients. As an example, in patient 1, a lytic skull lesion showed 68Ga-DOTA-F(ab′)2-trastuzumab uptake (SUV=3.42) (Fig. 4). In patient 2, who had multiple bilateral parenchymal lung nodules consistent with metastases, only minimal 68Ga-DOTA-F(ab′)2-trastuzumab uptake was noted (SUV range 2.40–3.79) (Fig. 5).


Pilot study of 68Ga-DOTA-F(ab')2-trastuzumab in patients with breast cancer.

Beylergil V, Morris PG, Smith-Jones PM, Modi S, Solit D, Hudis CA, Lu Y, O'Donoghue J, Lyashchenko SK, Carrasquillo JA, Larson SM, Akhurst TJ - Nucl Med Commun (2013)

Lytic lesion in the left calvarium with 68Ga-DOTA-F(ab′)2-trastuzumab uptake (patient 1). 68Ga-DOTA-F(ab′)2-trastuzumab, 68Ga-1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-F(ab′)2-trastuzumab.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3815146&req=5

Figure 4: Lytic lesion in the left calvarium with 68Ga-DOTA-F(ab′)2-trastuzumab uptake (patient 1). 68Ga-DOTA-F(ab′)2-trastuzumab, 68Ga-1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-F(ab′)2-trastuzumab.
Mentions: The visual analysis of the lesions is given in Table 1. In all, seven of 15 (47%) patients had HER2-negative breast cancer on histological analysis and did not show any tumor localization of 68Ga (Table 1). Eight (53%) patients were HER2 positive and three among them had ongoing therapy with trastuzumab at the time of scanning. One of the patients with HER2-positive breast cancer was trastuzumab naive, whereas all others had received prior treatment. All patients with HER2-positive disease had undergone recent 18F-FDG scans and all had 18F-FDG-avid disease. All seven patients with HER2-negative breast cancer also had 18F-FDG-positive disease. Only seven 18F-FDG-avid lesions showed appreciable 68Ga-DOTA-F(ab′)2-trastuzumab uptake in a total of four patients. As an example, in patient 1, a lytic skull lesion showed 68Ga-DOTA-F(ab′)2-trastuzumab uptake (SUV=3.42) (Fig. 4). In patient 2, who had multiple bilateral parenchymal lung nodules consistent with metastases, only minimal 68Ga-DOTA-F(ab′)2-trastuzumab uptake was noted (SUV range 2.40–3.79) (Fig. 5).

Bottom Line: The one patient who did not receive 68Ga-DOTA-F(ab')2-trastuzumab was excluded from analysis.It was determined that 68Ga-DOTA-F(ab')2-trastuzumab was well tolerated, with a T½ of ≈ 3.6 ± 0.9 h; the critical organ was the kidney, with a mean dose of 0.383 cGy/37 MBq; and tumor targeting was seen in 4/8 patients with HER2-positive disease.The reagent is safe, and assessments through additional studies in a better-defined group of patients, using larger administered masses of antibodies, with a better immunoreactive fraction are needed.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Radiology, Molecular Imaging and Therapy Service bDepartment of Medicine, Breast Cancer Medicine Service cHuman Oncology and Pathogenesis Program dDepartment of Medical Physics eRadiochemistry and Molecular Imaging Probes Core Facility, Memorial Sloan-Kettering Cancer Center Departments of fRadiology gMedicine, Weill Cornell Medical College, New York, New York, USA.

ABSTRACT

Objective: 68Ga-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-F(ab')2-trastuzumab [68Ga-DOTA-F(ab')2-trastuzumab] has been developed at our institution as a positron imaging reagent for assessing human epidermal growth factor receptor 2 (HER2) expression status by in-vivo imaging. Initial studies on animals demonstrated promising results in the monitoring of treatment response to heat shock protein 90-targeted drugs that inhibit the client protein HER2. We report here our initial clinical experience in the assessment of the toxicity, pharmacokinetics, biodistribution, and dosimetry profile of 68Ga-DOTA-F(ab')2-trastuzumab with PET/computed tomography using a mean of 236 MBq/5 mg administered intravenously.

Materials and methods: A group of 16 women with breast cancer were enrolled in this study. The one patient who did not receive 68Ga-DOTA-F(ab')2-trastuzumab was excluded from analysis. Both HER2-negative (n=7) and HER2-positive (n=8) cases were studied. Among the latter, seven had undergone trastuzumab treatment previously and one had not.

Results: It was determined that 68Ga-DOTA-F(ab')2-trastuzumab was well tolerated, with a T½ of ≈ 3.6 ± 0.9 h; the critical organ was the kidney, with a mean dose of 0.383 cGy/37 MBq; and tumor targeting was seen in 4/8 patients with HER2-positive disease.

Conclusion: The reagent is safe, and assessments through additional studies in a better-defined group of patients, using larger administered masses of antibodies, with a better immunoreactive fraction are needed.

Show MeSH
Related in: MedlinePlus