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Review of salvage therapy for biochemically recurrent prostate cancer: the role of imaging and rationale for systemic salvage targeted anti-prostate-specific membrane antigen radioimmunotherapy.

Kosuri S, Akhtar NH, Smith M, Osborne JR, Tagawa ST - Adv Urol (2012)

Bottom Line: One significant issue in this setting is the lack of reliable imaging biomarkers to guide the use of local salvage therapy, as the likely reason for a low cure rate is the presence of undetected micrometastatic disease outside of the prostate/prostate bed.Prostate-specific membrane antigen (PSMA) is highly overexpressed by the majority of prostate cancers.While initial methods of exploiting PSMA's high and selective expression were suboptimal, additional work in both imaging and therapeutics is progressing.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.

ABSTRACT
Despite local therapy with curative intent, approximately 30% of men suffer from biochemical relapse. Though some of these PSA relapses are not life threatening, many men eventually progress to metastatic disease and die of prostate cancer. Local therapy is an option for some men, but many have progression of disease following local salvage attempts. One significant issue in this setting is the lack of reliable imaging biomarkers to guide the use of local salvage therapy, as the likely reason for a low cure rate is the presence of undetected micrometastatic disease outside of the prostate/prostate bed. Androgen deprivation therapy is a cornerstone of therapy in the salvage setting. While subsets may benefit in terms of delay in time to metastatic disease and/or death, research is ongoing to improve salvage systemic therapy. Prostate-specific membrane antigen (PSMA) is highly overexpressed by the majority of prostate cancers. While initial methods of exploiting PSMA's high and selective expression were suboptimal, additional work in both imaging and therapeutics is progressing. Salvage therapy and imaging modalities in this setting are briefly reviewed, and the rationale for PSMA-based systemic salvage radioimmunotherapy is described.

No MeSH data available.


Related in: MedlinePlus

Anterior (a) and posterior (b) planar gamma camera images of radiolabeled J591. A greater number of lesions are apparent compared to anterior (c) and posterior (d) 99mTc-MDP bone scan. Hepatic clearance of radiolabeled mAb results in nonspecific uptake in the liver.
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fig1: Anterior (a) and posterior (b) planar gamma camera images of radiolabeled J591. A greater number of lesions are apparent compared to anterior (c) and posterior (d) 99mTc-MDP bone scan. Hepatic clearance of radiolabeled mAb results in nonspecific uptake in the liver.

Mentions: A major reason for the suboptimal results with capromab pendetide lies with its targeting of the internal domain of PSMA, leading to the inability to bind to viable cells [32–35, 46]. Recognition of these features led to the development of mAbs by Bander et al. to the exposed, extracellular domain of PSMA [46–48]. J591, a deimmunized mAb against the extracellular domain of PSMA, has been the lead clinical candidate [48, 49]. While no formal prostate imaging studies of J591 have been conducted, several therapeutic studies examining the clinical utility of radiolabeled J591 have been performed with built-in imaging components [49–51]. Radiolabeled J591 has successfully targeted (imaged) 89–100% osseous targeting and 69–100% soft tissue targeting [49–51], including cases where J591 demonstrated lesions that were not apparent on the bone scan but were identified on subsequent MR or conventional imaging as the lesion progressed (Figure 1) [52]. Current imaging work with anti-PSMA mAbs involves immune-PET imaging [53, 54]. Additional studies utilize small molecule inhibitors, including 123I-MIP-1072, 123I-MIP-1095, 99mTc-MIP-1404, and 99mTc-MIP-1405 [55, 56].


Review of salvage therapy for biochemically recurrent prostate cancer: the role of imaging and rationale for systemic salvage targeted anti-prostate-specific membrane antigen radioimmunotherapy.

Kosuri S, Akhtar NH, Smith M, Osborne JR, Tagawa ST - Adv Urol (2012)

Anterior (a) and posterior (b) planar gamma camera images of radiolabeled J591. A greater number of lesions are apparent compared to anterior (c) and posterior (d) 99mTc-MDP bone scan. Hepatic clearance of radiolabeled mAb results in nonspecific uptake in the liver.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368159&req=5

fig1: Anterior (a) and posterior (b) planar gamma camera images of radiolabeled J591. A greater number of lesions are apparent compared to anterior (c) and posterior (d) 99mTc-MDP bone scan. Hepatic clearance of radiolabeled mAb results in nonspecific uptake in the liver.
Mentions: A major reason for the suboptimal results with capromab pendetide lies with its targeting of the internal domain of PSMA, leading to the inability to bind to viable cells [32–35, 46]. Recognition of these features led to the development of mAbs by Bander et al. to the exposed, extracellular domain of PSMA [46–48]. J591, a deimmunized mAb against the extracellular domain of PSMA, has been the lead clinical candidate [48, 49]. While no formal prostate imaging studies of J591 have been conducted, several therapeutic studies examining the clinical utility of radiolabeled J591 have been performed with built-in imaging components [49–51]. Radiolabeled J591 has successfully targeted (imaged) 89–100% osseous targeting and 69–100% soft tissue targeting [49–51], including cases where J591 demonstrated lesions that were not apparent on the bone scan but were identified on subsequent MR or conventional imaging as the lesion progressed (Figure 1) [52]. Current imaging work with anti-PSMA mAbs involves immune-PET imaging [53, 54]. Additional studies utilize small molecule inhibitors, including 123I-MIP-1072, 123I-MIP-1095, 99mTc-MIP-1404, and 99mTc-MIP-1405 [55, 56].

Bottom Line: One significant issue in this setting is the lack of reliable imaging biomarkers to guide the use of local salvage therapy, as the likely reason for a low cure rate is the presence of undetected micrometastatic disease outside of the prostate/prostate bed.Prostate-specific membrane antigen (PSMA) is highly overexpressed by the majority of prostate cancers.While initial methods of exploiting PSMA's high and selective expression were suboptimal, additional work in both imaging and therapeutics is progressing.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.

ABSTRACT
Despite local therapy with curative intent, approximately 30% of men suffer from biochemical relapse. Though some of these PSA relapses are not life threatening, many men eventually progress to metastatic disease and die of prostate cancer. Local therapy is an option for some men, but many have progression of disease following local salvage attempts. One significant issue in this setting is the lack of reliable imaging biomarkers to guide the use of local salvage therapy, as the likely reason for a low cure rate is the presence of undetected micrometastatic disease outside of the prostate/prostate bed. Androgen deprivation therapy is a cornerstone of therapy in the salvage setting. While subsets may benefit in terms of delay in time to metastatic disease and/or death, research is ongoing to improve salvage systemic therapy. Prostate-specific membrane antigen (PSMA) is highly overexpressed by the majority of prostate cancers. While initial methods of exploiting PSMA's high and selective expression were suboptimal, additional work in both imaging and therapeutics is progressing. Salvage therapy and imaging modalities in this setting are briefly reviewed, and the rationale for PSMA-based systemic salvage radioimmunotherapy is described.

No MeSH data available.


Related in: MedlinePlus