mAb J591 Research Articles

Increased utilization of prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (PSMA-TRT) in African American (AA) patients at an academic medical center.

36 Background: At Weill Cornell Medicine (WCM), we have had a research program utilizing anti-PSMA mAb J591 since the year 2000. With the addition of PSMA ligand-based therapies in 2017, we have enrolled around 300 patients on investigational PSMA-TRT clinical trials. Since the approval of 177Lu-PSMA-617 (Pluvicto; Lu-177 vipivotide tetraxetan), we began standard-of-care (SOC) treatment, co-enrolling willing patients into a research registry. Recognizing the low numbers of AA patients enrolled on therapeutic clinical trials in the U.S., we made a concerted effort to increase the number of AA patients with prostate cancer (PC) enrolled on clinical trials at WCM. We retrospectively assessed the demographic data of patients enrolled on PSMA-TRT clinical trials to determine changing patterns of enrollment, and to determine if our efforts have improved access to these novel treatments for this under-represented, but high-risk population of patients. Methods: We collected demographic data (namely race and ethnicity) on patients with PC from WCM who were included on our PSMA-TRT investigational clinical trial databases or enrolled on our SOC 177Lu-PSMA-617 research registry. We used self-reported race and, when not available (due to patient death or loss of follow-up), demographic information documented in the medical record. Patients were grouped into 5-year cohorts based on either the date of consent for trial enrollment, or the start date of PSMA-TRT treatment (based on available information). Institutional tumor registry data was used as a comparator to assess the total percentage of AA patients with PC seen at WCM. Results: The percentages of patients included on PSMA-TRT clinical trials at WCM who were identified as AA were as follows: 2000-2004: 3.1% (2/65), 2005-2009: 5.1% (3/59), 2010-2014: 6.1% (2/33), and 2015-2019: 5.9% (5/85). The percentage of AA patients on PSMA-TRT studies from 2020 through July 2022 was 18.2% (16/88, inclusive of 8/72 investigational TRT subjects and 8/16 SOC registry participants). The total percentages of AA patients seen at Cornell based upon analysis of our tumor registry data were as follows: 2000-2004: 10.5% (182/1728), 2005-2009: 6.9% (250/3607), 2010-2014: 10% (326/3255), 2015-2019: 11.5% (278/2413), and 2020: 14.1%. Tumor registry data for 2021-present were not yet available. Conclusions: The percentage of AA patients on investigational PSMA-TRT trials at our institution notably increased from 2000-2019 (3.1%-6.1%) to 2020-2022 (11.1%). Moreover, 50% of those treated with 177Lu-PSMA-617 since its FDA approval and co-enrolled on our research registry identified as AA. These data suggest that outreach and increasing access to AA patients for novel PC treatment such as PSMA-TRT can result in increased numbers of underrepresented patients enrolling on clinical trials and receiving the most modern standards of care (i.e., PSMA-TRT).

Randomized, double-blinded phase II study of ketoconazole (keto), hydrocortisone (HC), and anti-PSMA antibody J591 labeled with 177Lu or 111In in patients (pts) with high-risk non-metastatic (met) castration-resistant prostate cancer (M0 CRPC).

LBA21 Background: Up to 1/3 of pts develop biochemical relapse following primary therapy. Many are not cured with salvage local therapy, likely because of undetectable distant disease. PSMA is expressed on most PC and can be targeted by radiolabeled J591. 177Lu is a predominantly β-emitting radionuclide and also has γ emission which allows imaging. 111In is predominantly a γ emitter, also with some auger emission for therapy. Hormonal therapy is effective and may increase PSMA expression and radiosensitize. In this DOD-funded study initiated in the pre-PSMA PET and AR signaling inhibitor era, we hypothesized that 177Lu prolongs 18-month (mo) met-free survival (MFS) more than 111In in pts with high risk, M0 CRPC when targeting PSMA via J591 in combo with keto and HC. Methods: Pts with high-risk M0 CRPC defined by PSA DT < 8 mo and/or absolute PSA > 20 ng/mL and serum testosterone < 50 ng/mL with no evidence of metastatic disease on CT/MRI and bone scan were eligible. Treatment included a minimum 4 week lead-in with keto 400 mg TID and HC 20 mg AM, 10 mg PM (both of which could be continued until unacceptable toxicity or development of mets) and a single infusion of J591 with 2:1 randomization to 177Lu (70 mCi/m2) or 111In (5 mCi) in double-blinded fashion. The final version of the protocol was designed to randomize 55 pts for 80% power to detect a difference in 18-mo MFS with one-sided alpha of 10%. Secondary endpoints include median MFS, PSA response, overall survival, and toxicity. Results: 55 pts with median age 68 (range 52 - 88), 75% prostatectomy, 23% primary radiation, 2% primary ADT; 19% local salvage therapy. Median PSA doubling time 3 mo (range 0.87 – 7.85), median baseline PSA 8.0 (range 1-78). In intent to treat analysis (5 without imaging and 4 lost to follow up by 18 mo), 50% developed mets by 18 mo with 177Lu vs 76% with 111In (p=0.066). Median MFS was 23.8 mo vs 20.8 mo, and biochemical PFS was 18.67 vs 8.87 mo, favoring 177Lu in analyses censoring start of new treatment. Confirmed >50% PSA decline occurred in 82% with 177Lu and 71% with 111In. Grade >3 heme AEs were more common with 177Lu vs 111In, including neutropenia (57% vs 11%, with 1 febrile neutropenia) and thrombocytopenia (77% vs 11%, with 25% vs 6% platelet transfusions), whereas Gr >3 non-heme AEs were less common with 177Lu vs 111In, including abdominal pain (0 vs 11%), ALT increase (3.3% vs 22%), and diarrhea (0 vs 22%). Conclusions: Anti-PSMA mAb J591 with keto/HC when radiolabeled with 177Lu leads to improved 18-month met-free survival vs 111In. Most pts had significant PSA decline with either version of radiolabeled J591 with keto/HC. Hematologic toxicity is more common with 177Lu. This supports the development of anti-PSMA radioimmunotherapy for low volume advanced PC, though the optimal radionuclide and targeting agent is unknown. Clinical trial information: NCT00859781 .

Phase I/II trial of pembrolizumab and AR signaling inhibitor +/- 225Ac-J591 for chemo-naive metastatic castration-resistant prostate cancer (mCRPC).

TPS216 Background: The role of immune checkpoint inhibition (ICI) in prostate cancer remains undefined outside of the subset with mismatch repair. Several studies have suggested that ICI combined with androgen receptor signaling inhibitors (ARSI) or kinase inhibitors may result in improved and/or more durable response in a proportion of men with mCRPC. While not yet proven, addition of external beam radiation to ICI may improve outcomes (for instance Kwon et al Lancet Oncol 2014, Fizazi K et al, Eur Urol 2020). PSMA targeted therapy with 177Lu-PSMA-617 improves survival in men with CRPC, has been combined with ICI in early phase studies, and we have previously demonstrated the benefit of PSMA targeted therapy using radiolabeled mAb J591. PSMA-targeted alpha-emitters have a very high potency and the potential to generate immune response. Based upon i) ARSI may increase PSMA expression, ii) ARSI may radiosensitize tumors, iii) ARSI resistance may lead to increased PD-L1 expression, and iv) alpha emitters may generate an immune response, we hypothesize that the addition of an alpha-emitting radionuclide (225Ac) targeting prostate cancer (i.e PSMA+ tumors targeted with J591) will lead to double-stranded DNA breaks, cell death, and subsequent release of neoantigens, and thus will increase the response proportion to pembrolizumab plus ARSI resulting in more durable response. Methods: Key eligibility criteria include progressive mCRPC by PCWG3 on at least 1 prior AR pathway inhibitor and no prior chemotherapy for mCRPC. A phase I dose-finding study will first test safety of the triplet combination of pembrolizumab, an ARSI of physician choice, and 2 different doses of 225Ac-J591 (one with minimal and one with moderate single-agent toxicity). Following determination of the optimal dose, a randomized phase II trial will treat subjects with a fixed dose of pembrolizumab 400 mg every 6 weeks (for up to 2 years) plus a standard ARSI (until progression or intolerance) with or without 225Ac-J591. The primary endpoint of the study will test the hypothesis that the addition of a PSMA-targeted alpha emitter increases the composite of RECIST measurable disease, PSA, and CTC count response to immuno-hormonal therapy with 90% power. Key secondary clinical endpoints include 1-year progression-free survival, duration of response, and overall survival. Exploratory objectives include assessment of immunogenic cell death, immune serologic and host microbiome changes, plasma ctDNA, serial PSMA PET, and patient reported outcomes (FACT-P, BPI, EQ-5D-5L). The phase I portion of this DOD-funded study was activated in summer 2021 with the randomized phase II portion expected to open at PCCTC sites in 2022. Clinical trial information: NCT04946370.

Phase I dose-escalation study of 225Ac-J591 for progressive metastatic castration resistant prostate cancer (mCRPC).

TPS399 Background: PC is a radiosensitive disease. PSMA is overexpressed in advanced PC with upregulation by androgen receptor (AR) pathway dysregulation; limited expression exists in other organs. A series of sequential studies of beta-emitting radiolabeled anti-PSMA monoclonal antibody (mAb) J591 have demonstrated accurate targeting, efficacy with dose-response effect, and safety with predictable, reversible dose-limiting myelosuppression. Alpha emitters are significantly more potent with a shorter range than beta emitters. Though there is no direct tumor-targeting, the bone-targeting alpha emitter Ra223 is approved. Anecdotal reports of PSMA small molecule targeted alpha emitters have hinted at efficacy but are limited by xerostomia and in mouse models may lead to long-term renal damage. Intact mAb J591 has comparatively no to minimal distribution in salivary glands and kidneys. Preclinical studies demonstrated purity, immunoreactivity, and stability with efficacy in a xenograft model [AACR 2017]. Methods: Men with progressive mCRPC following at least 1 potent AR-targeted agent (e.g. abi/enza) and docetaxel (or unfit/refuse chemo) without limit of # prior therapies (excluding beta-emitting bone-targeted radioisotopes) provided adequate organ function will undergo imaging with 68Ga-PSMA-11 PET/CT followed by a single dose of 225Ac-J591. Single-subject cohorts will be enrolled until grade > 1 attributable toxicity, then transition to 3+3 design. Cohort 1 = 13.3 KBq/kg with planned escalation up to 93.3 KBq/kg of 225Ac with fixed 20 mg J591. Dose-limiting toxicity (DLT) is defined as attributable grade 4 heme toxicity or grade 3/4 non-heme toxicity. Planned cohort expansion will occur at recommended phase 2 dose (RP2D) in a 2-stage design. The primary endpoint is determination of DLT and RP2D. Secondary endpoints include toxicity, PSA decline rate, RECIST response, PFS, rPFS, OS, and patient reported outcomes (FACT-P and BPI-SF). Correlatives include baseline/follow up PSMA imaging, CTC count (CellSearch) changes, tissue and circulating genomic assessment, and immune studies. Enrollment began in October, 2017. Clinical trial information: NCT03276572.

Novel Monoclonal Antibodies Recognizing Human Prostate-Specific Membrane Antigen (PSMA) as Research and Theranostic Tools.

Prostate-specific membrane antigen (PSMA) is a validated target for the imaging and therapy of prostate cancer. Here, we report the detailed characterization of four novel murine monoclonal antibodies (mAbs) recognizing human PSMA as well as PSMA orthologs from different species. Performance of purified mAbs was assayed using a comprehensive panel of in vitro experimental setups including Western blotting, immunofluorescence, immunohistochemistry, ELISA, flow cytometry, and surface-plasmon resonance. Furthermore, a mouse xenograft model of prostate cancer was used to compare the suitability of the mAbs for in vivo applications. All mAbs demonstrate high specificity for PSMA as documented by the lack of cross-reactivity to unrelated human proteins. The 3F11 and 1A11 mAbs bind linear epitopes spanning residues 226-243 and 271-288 of human PSMA, respectively. 3F11 is also suitable for the detection of PSMA orthologs from mouse, pig, dog, and rat in experimental setups where the denatured form of PSMA is used. 5D3 and 5B1 mAbs recognize distinct surface-exposed conformational epitopes and are useful for targeting PSMA in its native conformation. Most importantly, using a mouse xenograft model of prostate cancer we show that both the intact 5D3 and its Fab fragment are suitable for in vivo imaging. With apparent affinities of 0.14 and 1.2 nM as determined by ELISA and flow cytometry, respectively, 5D3 has approximately 10-fold higher affinity for PSMA than the clinically validated mAb J591 and, therefore, is a prime candidate for the development of next-generation theranostics to target PSMA. Prostate 77:749-764, 2017. © 2017 Wiley Periodicals, Inc.

Design and preclinical evaluation of a 99mTc-labelled diabody of mAb J591 for SPECT imaging of prostate-specific membrane antigen (PSMA)

BackgroundSensitive and specific detection of nodal status, sites of metastases and low-volume recurrent disease could greatly improve management of patients with advanced prostate cancer. Prostate-specific membrane antigen (PSMA) is a well-established marker for prostate carcinoma with increased levels of expression in high-grade, hormone-refractory and metastatic disease. The monoclonal antibody (mAb) J591 is directed against an extracellular epitope of PSMA and has been shown to efficiently target disseminated disease including metastases in lymph nodes and bone. Its use as a diagnostic imaging agent however is limited due to its slow pharmacokinetics. In this study a diabody derived from mAb J591 was developed as a single photon emission computed tomography (SPECT) tracer with improved pharmacokinetics for the detection of PSMA expression in prostate cancer.MethodsA diabody in VH-VL orientation and with a C-terminal cysteine was expressed in HEK293T cells and purified by a combination of metal ion affinity and size exclusion chromatography. Specificity and affinity were determined in cell binding studies. For SPECT imaging, the diabody was site-specifically labelled with [99mTc(CO)3]+ via the C-terminal His tag and evaluated in a subcutaneous DU145/DU145-PSMA prostate carcinoma xenograft model.ResultsJ591C diabody binds to PSMA-expressing cells with low nanomolar affinity (3.3 ± 0.2 nM). SPECT studies allowed imaging of tumour xenografts with high contrast from 4 h post injection (p.i.). Ex vivo biodistribution studies showed peak tumour uptake of the tracer of 12.1% ± 1.7% injected dose (ID)/g at 8 h p.i. with a tumour to blood ratio of 8.0. Uptake in PSMA-negative tumours was significantly lower with 6.3% ± 0.5% at 8 h p.i. (p < 0.001).ConclusionThe presented diabody has favourable properties required to warrant its further development for antibody-based imaging of PSMA expression in prostate cancer, including PSMA-specific uptake, favourable pharmacokinetics compared to the parental antibody and efficient site-specific radiolabelling with 99mTc.

Synthesis and in vitro evaluation of MR molecular imaging probes using J591 mAb‐conjugated SPIONs for specific detection of prostate cancer

Carcinoma of the prostate is the most frequent diagnosed malignant tumor in men and is the second leading cause of cancer-related death in this group. The cure rate of prostate cancer is highly dependent on the stage of disease at the diagnosis and early detection is key to designing effective treatment strategies. The objective of the present study is to make a specific MR imaging probe for targeted imaging of cancer cells. We take advantage of the fact that many types of prostate cancer cells express high levels of prostate-specific membrane antigen (PSMA) on their cell surface. The imaging strategy is to use superparamagnetic iron oxide nanoparticles (SPIONs), attached to an antibody (J591) that binds to the extracellular domain of PSMA, to specifically enhance the contrast of PSMA-expressing prostate cancer cells. Conjugation of mAb J591 to commercial SPIONs was achieved using a heterobifunctional linker, sulfo-SMCC. Two types of prostate cancer cell lines were chosen for experiments: LNCaP (PSMA+) and DU145 (PSMA-). MRI and cell uptake experiments demonstrated the high potential of the synthesized nanoprobe as a specific MRI contrast agent for detection of PSMA-expressing prostate cancer cells.

Abstract 296: Characterization of prostate cancer circulating tumor cells using E-selectin coated-microtubes

Abstract Background: Metastasis and invasion is facilitated by adhesion of circulating tumor cells (CTCs) to endothelial cells in the blood vessel. Initial recruitment of CTCs to the blood vessel endothelium is mediated through selectin proteins. We used microtube coated with selectin proteins to simulate CTC adhesion under flow, to elucidate the complex physicochemical dynamics that control CTC adhesion in the bloodstream. Methods: Sterilized microrenathane microtubes were functionalized by E-selectin +/- anti-PSMA (mAb J591) and anti-EpCAM antibodies. Functionalized microtubes were used to observe the rolling behavior of prostate cancer cell lines MDAPCa2b, LNCaP C4-2, and PC-3. MDAPCa2b cells alone or mixed with normal peripheral blood mononuclear cells (PBMCs) were incubated with fluorescently conjugated mAbJ591, and the mixture flowed through the microtube for identification and capture efficiency. PBMCs isolated from prostate cancer patient's blood were similarly processed. Results: MDAPCa2b cells showed robust rolling at 1 dyne/cm2 shear stress while LNCaP, C4-2, and PC-3 cells did not exhibit rolling behavior on E-selectin coated microtubes. 7.5 cells were observed rolling at 1 dyne/cm2 compared to 1.5 cells at 8 dyne/cm2 per 100 mm2 area. To determine if prostate cancer cells could be identified in a mixture of PBMCs, MDAPCa2b cells were spiked in PBMCs and labeled with fluorescently conjugated mAb J591. MDAPCa2b cells demonstrated selective fluorescence which did not alter their rolling behavior. A 50% capture efficiency of MDAPCa2b cells spiked in PBMCs was achieved when flowed through E-selectin and anti-PSMA coated microtube. After establishing rolling and selective fluorescence in prostate cancer cell line, we used prostate cancer patient's blood. CTCs in prostate cancer patient's blood showed rolling behavior on E-selectin coated microtube. Further, these CTCs were PSMA-positive after incubation with fluorescently conjugated mAbJ591 and easily identified during the flow through the microtube. Conclusion: Our data shows that CTCs in prostate cancer patients exhibit rolling behavior, which may facilitate invasion and metastasis. Further, selective ex vivo labeling of CTCs enables rapid identification for subsequent characterization of their adhesion and invasive phenotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 296. doi:10.1158/1538-7445.AM2011-296

Phase II trial of the anti-prostate specific membrane antigen (PSMA) monoclonal antibody (mAb) J591 plus low-dose interleukin-2 (IL-2) in patients (pts) with recurrent prostate cancer (PC)

15558 Background: The de-immunized mAb J591 recognizes the extracellular domain of PSMA and was engineered to induce antibody-dependent cellular cytotoxicity (ADCC). Low-dose IL-2 results in the clonal expansion of NK cells and may enhance ADCC. We conducted a phase 2 trial to determine the efficacy and toxicity of mAb J591 plus low-dose subcutaneous (SC) IL-2 in pts with recurrent PC. Methods: 17 pts with recurrent PC (2 groups: 11 with PSA relapse only; and 6 with progressive castrate metastatic disease) received continuous low-dose SC IL-2 (1.2 x 106 IU/m2/day) daily for 8 weeks with mAb J591 (25 mg/m2 IV) weekly on weeks 4, 5 and 6 (1 cycle). Pts could receive a maximum of 3 cycles. Results: 16 evaluable pts received up to 3 cycles of therapy (16 pts, one cycle, 9 two cycles and 2 three cycles). Toxicity was mild and limited to fatigue and injection site reactions. At the end of cycle 1, PSA was stable (-50%&lt;change in PSA&lt;25%) in 9 of 16 patients, with PSA declines up to 34%. No PSA decline &gt;50% was observed. A post-hoc analysis of PSA kinetics showed 5 patients had a reduction in their PSA slope of =25%; 8 of the remaining 11 patients demonstrated PSA stabilization (- 25%&lt;change in PSA slope&lt;25%). PSA response was most commonly observed during weeks 4–6 of the cycle correlating with mAb administration. Flow cytometric analysis of peripheral blood mononuclear cells revealed an average increase in absolute NK cell count of 107% at week 4 and 117% at the end of cycle 1. Conclusions: The combination of mAb J591 with low-dose IL-2 was well tolerated and inhibited PSA kinetics in some patients, however no responses were seen. Repetitive dosed mAb J591 is a viable strategy for use in combination with immune modulatory or other therapies in recurrent prostate cancer. No significant financial relationships to disclose.

Apical Transport and Folding of Prostate-specific Membrane Antigen Occurs Independent of Glycan Processing

Prostate-specific membrane antigen (PSMA) is an integral cell-surface membrane glycoprotein that is overexpressed in prostate carcinomas rendering it an appropriate target for antibody-based therapeutic strategies. The biosynthesis of PSMA in transfected COS-1 cells reveals a slow conversion of mannose-rich to complex glycosylated PSMA compatible with slow transport kinetics from the endoplasmic reticulum to the Golgi. Importantly, mannose-rich PSMA persists as a trypsin-sensitive protein throughout its entire life cycle, and only Golgi-located PSMA glycoforms acquire trypsin resistance. This resistance, used here as a tool to examine correct folding, does not depend on the type of glycosylation, because different PSMA glycoforms generated in the presence of inhibitors of carbohydrate processing in the Golgi are also trypsin resistant. The conformational transition of PSMA to a correctly folded molecule is likely to occur in the Golgi and does not implicate ER molecular chaperones, such as BiP. We show here that PSMA is not only heavily N-but also O-glycosylated. The question arising is whether glycans, which do not play a role in folding of PSMA, are implicated in its transport to the cell surface. Neither the cell-surface expression of PSMA nor its efficient apical sorting in polarized Madin-Darby canine kidney cells are influenced by modulators of N- and O-glycosylation. The acquisition of folding determinants in the Golgi, therefore, is an essential prerequisite for protein trafficking and sorting of PSMA and suggests that altered or aberrant glycosylation often occurring during tumorigenesis has no regulatory effect on the cell-surface expression of PSMA.

Clinical Use of Monoclonal Antibody HuJ591 Therapy: Targeting Prostate Specific Membrane Antigen

Prostate specific membrane antigen (PSMA) is a cell surface peptidase highly expressed by malignant prostate epithelial cells and vascular endothelial cells of numerous solid tumor malignancies but not normal vascular endothelium in benign tissues or neoplastic epithelial cells of nonprostate malignancies. Monoclonal antibody (mAb) J591 recognizes the extracellular domain of PSMA. The current status of clinical trials using mAb J591 is reviewed. The mouse antibody was deimmunized by replacing murine immunoglobulin sequences with human immunoglobulin sequences, resulting in a nonimmunogenic antibody HuJ591. Results of completed and ongoing phase 1 and 2 clinical trials using mAb J591 are presented. A phase I clinical trial with murine J591 indicated that it possesses high affinity for prostate cancer metastases in bone and soft tissue. A phase I clinical trial showed that HuJ591 was well tolerated, demonstrated excellent targeting to disseminated prostate cancer sites and did not result in a host immune response to the antibody. A phase II clinical trial was initiated to study the efficacy of combining HuJ591 with low dose interleukin-2. Two phase I studies in patients with prostate cancer are in progress using the beta-emitting radiometals 90yttrium and 177lutetium linked via a DOTA chelate to HuJ591. Preliminary results from an ongoing phase I trial of 111indium labeled mAb HuJ591 in patients with advanced solid tumors showed that HuJ591 specifically targets nonprostate cancers. Early results of clinical studies indicate that mAb HuJ591 represents targeted therapy to PSMA and has therapeutic potential in prostate cancer and other urological and solid tumor malignancies.

Targeting Metastatic Prostate Cancer With Radiolabeled Monoclonal Antibody J591 to the Extracellular Domain of Prostate Specific Membrane Antigen

We performed an interim analysis of imaging data collected in 2 phase I radioimmunotherapy trials to determine the ability of monoclonal antibody (mAb) J591 directed to the extracellular domain of prostate specific membrane antigen (PSMA) to target sites of known metastatic prostate cancer accurately. Patients with progressing hormone independent prostate cancer were entered in 2 phase I dose finding trials with radiolabeled mAb J591. J591 is the first mAb targeting the extracellular domain of PSMA as well as the first de-immunized (humanized) mAb to PSMA to be tested in humans. These trials were primarily designed to assess dose limiting toxicity, maximum tolerated dose, pharmacokinetics and organ dosimetry. Planar gamma camera imaging studies obtained on the first 53 patients were reviewed and compared to sites of metastatic prostate cancer visualized on conventional imaging studies including bone scan, computerized tomography and/or magnetic resonance imaging. In 1 trial 29 patients received 111indium-J591 for imaging followed by 90yttrium-J591 for therapy. In the parallel trial 24 patients were treated with 177lutetium-J591, an isotope that can be imaged directly. Of 53 patients reviewed 46 (87%) had evidence of metastatic disease on conventional scans. Overall, of the 43 evaluable patients J591 accurately targeted bone and/or soft tissue lesions in 42 (98%). J591 accurately targeted bone lesions in 32 of 34 (94%) and soft tissue lesions in 13 of 18 (72%) evaluable patients. Radiolabeled J591 accurately targets bone and soft tissue metastatic prostate cancer sites, and may be useful for targeting therapeutic and/or diagnostic imaging agents.