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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

The average biological serum clearance curve for 68Ga-DOTA-F(ab′)2-trastuzumab from all 15 patients is plotted with SDs in both the time and %ID/l serum axis. 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 1: The average biological serum clearance curve for 68Ga-DOTA-F(ab′)2-trastuzumab from all 15 patients is plotted with SDs in both the time and %ID/l serum axis. 68Ga-DOTA-F(ab′)2-trastuzumab, 68Ga-1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-F(ab′)2-trastuzumab.

Mentions: Biological plasma clearance curves of the antibody are summarized as the mean±SD (Fig. 1). Compared with the radioactivity in the plasma at the initial 0.6±0.1 h time sampled, at 3.1±0.3 h after injection there was an average of 58.6±17% of the original activity left in the plasma volume, indicating that a mean of 41.4% of the radioactivity in the plasma at the end of the infusion had left the intravascular compartment. Summary pharmacokinetic parameters of 14 of the 15 patients are shown in Table 2; one patient was excluded because of outlying data that did not fit a single or biexponential clearance. The volume of distribution of the central compartment was 4.09±1.51 l, which was significantly greater than the plasma volume (2.34±0.12 l) (P<0.001, paired t-test).


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)

The average biological serum clearance curve for 68Ga-DOTA-F(ab′)2-trastuzumab from all 15 patients is plotted with SDs in both the time and %ID/l serum axis. 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 1: The average biological serum clearance curve for 68Ga-DOTA-F(ab′)2-trastuzumab from all 15 patients is plotted with SDs in both the time and %ID/l serum axis. 68Ga-DOTA-F(ab′)2-trastuzumab, 68Ga-1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-F(ab′)2-trastuzumab.
Mentions: Biological plasma clearance curves of the antibody are summarized as the mean±SD (Fig. 1). Compared with the radioactivity in the plasma at the initial 0.6±0.1 h time sampled, at 3.1±0.3 h after injection there was an average of 58.6±17% of the original activity left in the plasma volume, indicating that a mean of 41.4% of the radioactivity in the plasma at the end of the infusion had left the intravascular compartment. Summary pharmacokinetic parameters of 14 of the 15 patients are shown in Table 2; one patient was excluded because of outlying data that did not fit a single or biexponential clearance. The volume of distribution of the central compartment was 4.09±1.51 l, which was significantly greater than the plasma volume (2.34±0.12 l) (P<0.001, paired t-test).

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