"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

Neuropsychiatric Symptoms after Liver Transplantation in a 65-Year-Old Male Patient.

The development of immunosuppressants has been key for the advancement of solid organ transplant surgery. Specifically, cyclosporine, tacrolimus, or everolimus have significantly increased the survival rate of patients by reducing the risk of a rejection of the transplanted organ and limiting graft-versus-host disease. We report the case of a 65-year-old man who, after undergoing a liver transplantation and receiving an immunosuppressive treatment with cyclosporine and everolimus, presented severe obsessive, psychotic, and behavioral symptoms over the past three years, and describe the pharmacological and non-pharmacological interventions implemented against these symptoms. In this case, the immunosuppressants used have been cyclosporine and, preferably, everolimus. On the other hand, potential adverse reactions to the treatment have been observed, including neuropsychiatric symptoms such as tremor, anxiety, dysthymia, psychosis, and behavioral disorders, which make it necessary to use corrective psychoactive drugs such as benzodiazepines, antidepressants, and antipsychotics, combined with non-pharmacological interventions. A transversal approach, from the medical and psychosocial disciplines, facilitates success in managing neuropsychiatric symptoms after soft organ transplants.

Characteristics and management of Susac syndrome in an emergent country: a multi-center case series from Brazil.

BACKGROUND: Susac syndrome (SS) is a rare endotheliopathy with an estimated prevalence of 0.14-0.024 per 100,000. It is an important differential diagnosis in demyelinating disorders. There are few case series and no large randomized controlled trials, and most reports come from developed countries. We report six cases of SS in three centers in Brazil and discuss management challenges in emergent countries. METHODS: This is a retrospective case series of patients diagnosed with SS in three medical centers in Brazil between April 2018 and July 2021. The European Susac consortium (EuSaC) criteria were used for diagnosis of SS. Demographic data and clinical interventions were described and outcomes were assessed subjectively and by applying the modified Rankin Scale (mRS) on last follow-up. RESULTS: Six patients were diagnosed with SS (3 males, 3 females). Mean age at presentation was 36 years (range 17 to 54). The most common initial symptom was confusion, followed by visual impairment and hearing loss. Characteristic snowball lesions on magnetic resonance imaging (MRI) were present in four patients (66%). Retinal artery abnormalities were present in half (3/6) of patients, and sensorineural hearing loss was present in four patients (66%). Outcome was favorable (mRS ≤ 2) in five patients (86%). Patients treated early had a more favorable outcome. CONCLUSION: Emergent countries face challenges in the diagnosis and management of patients with SS, such as access to advanced tests (fluorescein angiography, serial MRI) and treatment drugs (rituximab, mycophenolate). Further research should consider particularities of patients with SS in emergent countries.

Asparagopsis Genus: What We Really Know About Its Biological Activities and Chemical Composition.

Although the genus Asparagopsis includes only two taxonomically accepted species, the published literature is unanimous about the invasive nature of this genus in different regions of the globe, and about the availability of large amounts of biomass for which it is important to find a commercial application. This review shows that extracts from Asparagospsis species have already been evaluated for antioxidant, antibacterial, antifungal, antiviral, antifouling, cytotoxic, antimethanogenic and enzyme-inhibitory activity. However, the tables presented herein show, with few exceptions, that the activity level displayed is generally low when compared with positive controls. Studies involving pure compounds being identified in Asparagopsis species are rare. The chemical compositions of most of the evaluated extracts are unknown. At best, the families of the compounds present are suggested. This review also shows that the volatile halogenated compounds, fatty acids and sterols that are biosynthesized by the Asparagopsis species are relatively well known. Many other non-volatile metabolites (halogen compounds, flavonoids, other phenolic compounds) seem to be produced by these species, but their chemical structures and properties haven'been investigated. This shows how much remains to be investigated regarding the secondary-metabolite composition of these species, suggesting further studies following more targeted methodologies.

Factors Related to Greater Functional Recovery after Suffering a Stroke.

BACKGROUND: In a stroke, the importance of initial functional status is fundamental for prognosis. The aim of the current study was to investigate functional status, assessed by the Functional Independence Measure (FIM) scale, and possible predictors of functional outcome at discharge from inpatient rehabilitation. METHODS: This is a retrospective study that was carried out at the Physical Medicine and Rehabilitation Service in A Coruña (Spain). A total of 365 consecutive patients with primary diagnosis of stroke were enrolled. The functional assessments of all patients were performed through the FIM. A descriptive and a bivariate analysis of the variables included in the study was made and a succession of linear regression models was used to determine which variables were associated with the total FIM at discharge. RESULTS: Prior to having the stroke, 76.7% were totally independent in activities of daily living. The FIM scale score was 52.5 ± 25.5 points at admission and 83.4 ± 26.3 at hospital discharge. The multivariate analysis showed that FIM scores on admission were the most important predictors of FIM outcomes. CONCLUSIONS: Our study indicates that the degree of independence prior to admission after suffering a stroke is the factor that will determine the functionality of patients at hospital discharge.

Apathy and agitation in institutionalized older adults: an empirically derived classification.

BACKGROUND: Apathy and agitation are often recognized as the most problematic behavioural and psychological symptoms in care settings. In this study, we analyze the relationship between apathy and agitation symptoms other and their relationship with demographic, cognitive, and neuropsychiatric variables and psychotropic medication use. METHODS: A retrospective study was conducted at a gerontological care centre in Láncara, Spain. Participants were 196 residents of the gerontological care centre, including 143 with a diagnosis of dementia. Apathy and agitation were assessed with the Apathy Scale for Institutionalized Patients with Dementia, Nursing Home version, and the Spanish version of the Cohen-Mansfield Agitation Inventory, respectively. Two-stage hierarchical cluster analysis (hierarchical cluster analysis in a first exploratory stage and K-means clustering to obtain the final solution in the second stage) was conducted to assign residents to different groups based on apathy and agitation scores. RESULTS: In cluster 1, a certain level of apathy, the highest levels of agitation, and the most frequent intake of atypical antipsychotics and clomethiazole were observed. The highest levels of apathy and the most frequent intake of memantine were seen in cluster 2. The lowest levels of agitation and apathy and the highest levels of cognitive performance were found in cluster 3. CONCLUSIONS: In this study, subjects with dementia were in a state of high agitation and eventual apathy, had low cognitive status, and were very old. Patients with this profile require well-designed non-pharmacological interventions.

Antibody Co-Administration Can Improve Systemic and Local Distribution of Antibody-Drug Conjugates to Increase In Vivo Efficacy.

Several antibody-drug conjugates (ADC) showing strong clinical responses in solid tumors target high expression antigens (HER2, TROP2, Nectin-4, and folate receptor alpha/FRα). Highly expressed tumor antigens often have significant low-level expression in normal tissues, resulting in the potential for target-mediated drug disposition (TMDD) and increased clearance. However, ADCs often do not cross-react with normal tissue in animal models used to test efficacy (typically mice), and the impact of ADC binding to normal tissue antigens on tumor response remains unclear. An antibody that cross-reacts with human and murine FRα was generated and tested in an animal model where the antibody/ADC bind both human tumor FRα and mouse FRα in normal tissue. Previous work has demonstrated that a "carrier" dose of unconjugated antibody can improve the tumor penetration of ADCs with high expression target-antigens. A carrier dose was employed to study the impact on cross-reactive ADC clearance, distribution, and efficacy. Co-administration of unconjugated anti-FRα antibody with the ADC-improved efficacy, even in low expression models where co-administration normally lowers efficacy. By reducing target-antigen-mediated clearance in normal tissue, the co-administered antibody increased systemic exposure, improved tumor tissue penetration, reduced target-antigen-mediated uptake in normal tissue, and increased ADC efficacy. However, payload potency and tumor antigen saturation are also critical to efficacy, as shown with reduced efficacy using too high of a carrier dose. The judicious use of higher antibody doses, either through lower DAR or carrier doses, can improve the therapeutic window by increasing efficacy while lowering target-mediated toxicity in normal tissue.

A Case Study on Polypharmacy and Depression in a 75-Year-Old Woman with Visual Deficits and Charles Bonnet Syndrome.

Depression is one of the most prevalent pathologies in older adults. Its diagnosis and treatment are complex due to different factors that intervene in its development and progression, including intercurrent organic diseases, perceptual deficits, use of drugs, and psycho-social conditions associated with the aging process. We present the case of a 75-year-old woman (who lives in the community) with a diagnosis of major depression with more than 10 years of history, analyzing her evolution and therapeutic approach.

Histomorphometric evaluation of human extraction sockets treated with autologous fibrin, sticky bone or biphasic calcium phosphate.

It is essential to maintain the alveolar bone ridge to ensure the success of implant therapy. Platelet-rich fibrin (PRF) may benefit bone repair, but its quantitative microscopic results are still inconclusive. The aim of this study was to histomorphometrically analyze human dental alveoli after extraction treated with autologous fibrin, biphasic calcium phosphate or sticky bone. The sample consisted of healthy adult volunteer patients, with clinical and tomographic indication for single post-extraction graft of upper premolars for maintenance of the alveolar ridge and subsequent implantation. The 10 remaining patients in the study were divided into three groups according to the type of filling used in the dental socket: autologous PRF plug covered by a PRF membrane (G1), PRF associated with an alloplastic graft based on hydroxyapatite with beta tricalcium phosphate covered by a collagen membrane (G2) or alloplastic graft based on beta tricalcium phosphate covered by collagen membrane (control). After 8 months, bone biopsies were performed at the grafted sites and the patients underwent implant-prosthetic rehabilitation. Paraffin-embedded tissue blocks were routinely processed and sectionsfrom different depths were mounted in 3 slides and stained with HE. The histomorphometric evaluation analyzed 30 photomicrographs per block, quantifying the percentage presence of newly formed bone, connective tissue and remaining biomaterial using the ImageJ software. Parametric data enabled intergroup comparisons using ANOVA and Tukey's post-hoc test for multiple comparison with statistical significance of 5% (p<0.05), with normality of the 3 groups by the Jarque-Bera test (p>0.05). There was a higher mean of newly formed bone in G1 (68.83%) compared to G2 (35.69%) and control (16.28%). There was greater presence of connective tissue in the control (61.56%). Remaining biomaterial was higher in G2 (15.75%), but did not differ statistically from the control. Bone regeneration obtained with PRF alone or sticky bone suggests the efficacy of these therapies, encouraging the clinical use of this blood concentrate in dental procedures.

A manutenção do rebordo ósseo alveolar é prerrogativa para o sucesso da terapia com implantes. A fibrina rica em plaquetas (PRF) poderia beneficiar o reparo ósseo, mas seus resultados microscópicos quantitativos são ainda inconclusivos. O objetivo deste trabalho foi analisar histomorfometricamente alvéolos dentários humanos pós-extração tratados com fibrina autóloga, fosfato de cálcio bifásico ou sua associação. A amostra consistiu de pacientes adultos voluntários saudáveis, com indicação clínica e tomográfica de enxerto unitário pós-exodontia de pré-molares superiores para manutenção de rebordo alveolar e posterior implante. Os 10 pacientes remanescentes no estudo foram divididos em 3 grupos de acordo com o tipo de preenchimento usado no alvéolo dentário: plug de PRF autóloga recoberto por membrana de PRF (G1), PRF associada a enxerto aloplástico de hidroxiapatita com beta fosfato tricálcio recoberto por membrana de colágeno (G2) ou enxerto aloplástico de beta fosfato tricálcio recoberto por membrana de colágeno (controle). Após 8 meses, foram realizadas biópsias ósseas nos locais enxertados e os pacientes seguiram a reabilitação implanto-protético. Blocos histológicos incluídos em parafina foram microtomizados para gerar 3 lâminas de secções em diferentes profundidades, que foram coradas em HE. A avaliação histomorfométrica analisou 30 fotomicrografias por bloco, quantificando a presença percentual de osso neoformado, tecido conjuntivo e biomaterial remanescente pelo programa ImageJ. Os dados paramétricos permitiram comparações intergrupos usando ANOVA e pós-teste de comparações múltiplas de Tukey com significância estatística de 5% (p<0,05), havendo normalidade dos 3 grupos pelo teste Jarque-Bera (p>0,05). Houve maior média de osso neoformado em G1 (68,83%) em comparação a G2 (35,69%) e controle (16,28%). Houve maior presença de tecido conjuntivo no controle (61,56 %). Biomaterial remanescente foi maior em G2 (15,75%), mas não diferiu estatisticamente para o controle. A regeneração óssea obtida com PRF isolada ou em associação sugere a eficácia destas terapias, encorajando o uso clínico deste concentrado sanguíneo em procedimentos odontológicos.

Histomorphometric evaluation of human extraction sockets treated with autologous fibrin, sticky bone or biphasic calcium phosphate / Avaliação histomorfométrica de alvéolos dentários humanos pós-extração tratados com fibrina autóloga, aglutinado ósseo ou fosfato de cálcio bifásico

ABSTRACT It is essential to maintain the alveolar bone ridge to ensure the success of implant therapy. Platelet-rich fibrin (PRF) may benefit bone repair, but its quantitative microscopic results are still inconclusive. The aim of this study was to histomorphometrically analyze human dental alveoli after extraction treated with autologous fibrin, biphasic calcium phosphate or sticky bone. The sample consisted of healthy adult volunteer patients, with clinical and tomographic indication for single post-extraction graft of upper premolars for maintenance of the alveolar ridge and subsequent implantation. The 10 remaining patients in the study were divided into three groups according to the type of filling used in the dental socket: autologous PRF plug covered by a PRF membrane (G1), PRF associated with an alloplastic graft based on hydroxyapatite with beta tricalcium phosphate covered by a collagen membrane (G2) or alloplastic graft based on beta tricalcium phosphate covered by collagen membrane (control). After 8 months, bone biopsies were performed at the grafted sites and the patients underwent implant-prosthetic rehabilitation. Paraffin-embedded tissue blocks were routinely processed and sectionsfrom different depths were mounted in 3 slides and stained with HE. The histomorphometric evaluation analyzed 30 photomicrographs per block, quantifying the percentage presence of newly formed bone, connective tissue and remaining biomaterial using the ImageJ software. Parametric data enabled intergroup comparisons using ANOVA and Tukey's post-hoc test for multiple comparison with statistical significance of 5% (p<0.05), with normality of the 3 groups by the Jarque-Bera test (p>0.05). There was a higher mean of newly formed bone in G1 (68.83%) compared to G2 (35.69%) and control (16.28%). There was greater presence of connective tissue in the control (61.56%). Remaining biomaterial was higher in G2 (15.75%), but did not differ statistically from the control. Bone regeneration obtained with PRF alone or sticky bone suggests the efficacy of these therapies, encouraging the clinical use of this blood concentrate in dental procedures.

RESUMO A manutenção do rebordo ósseo alveolar é prerrogativa para o sucesso da terapia com implantes. A fibrina rica em plaquetas (PRF) poderia beneficiar o reparo ósseo, mas seus resultados microscópicos quantitativos são ainda inconclusivos. O objetivo deste trabalho foi analisar histomorfometricamente alvéolos dentários humanos pós-extração tratados com fibrina autóloga, fosfato de cálcio bifásico ou sua associação. A amostra consistiu de pacientes adultos voluntários saudáveis, com indicação clínica e tomográfica de enxerto unitário pós-exodontia de pré-molares superiores para manutenção de rebordo alveolar e posterior implante. Os 10 pacientes remanescentes no estudo foram divididos em 3 grupos de acordo com o tipo de preenchimento usado no alvéolo dentário: plug de PRF autóloga recoberto por membrana de PRF (G1), PRF associada a enxerto aloplástico de hidroxiapatita com beta fosfato tricálcio recoberto por membrana de colágeno (G2) ou enxerto aloplástico de beta fosfato tricálcio recoberto por membrana de colágeno (controle). Após 8 meses, foram realizadas biópsias ósseas nos locais enxertados e os pacientes seguiram a reabilitação implanto-protético. Blocos histológicos incluídos em parafina foram microtomizados para gerar 3 lâminas de secções em diferentes profundidades, que foram coradas em HE. A avaliação histomorfométrica analisou 30 fotomicrografias por bloco, quantificando a presença percentual de osso neoformado, tecido conjuntivo e biomaterial remanescente pelo programa ImageJ. Os dados paramétricos permitiram comparações intergrupos usando ANOVA e pós-teste de comparações múltiplas de Tukey com significância estatística de 5% (p<0,05), havendo normalidade dos 3 grupos pelo teste Jarque-Bera (p>0,05). Houve maior média de osso neoformado em G1 (68,83%) em comparação a G2 (35,69%) e controle (16,28%). Houve maior presença de tecido conjuntivo no controle (61,56 %). Biomaterial remanescente foi maior em G2 (15,75%), mas não diferiu estatisticamente para o controle. A regeneração óssea obtida com PRF isolada ou em associação sugere a eficácia destas terapias, encorajando o uso clínico deste concentrado sanguíneo em procedimentos odontológicos.

Peptide-Cleavable Self-immolative Maytansinoid Antibody-Drug Conjugates Designed To Provide Improved Bystander Killing.

A new type of antibody-drug conjugate (ADC) has been prepared that contains a sulfur-bearing maytansinoid attached to an antibody via a highly stable tripeptide linker. Once internalized by cells, proteases in catabolic vesicles cleave the peptide of the ADC's linker causing self-immolation that releases a thiol-bearing metabolite, which is then S-methylated. Conjugates were prepared with peptide linkers containing only alanyl residues, which were all l isomers or had a single d residue in one of the three positions. A d-alanyl residue in the linker did not significantly impair a conjugate's cytotoxicity or bystander killing unless it was directly attached to the immolative moiety. Increasing the number of methylene units in the maytansinoid side chain of a conjugate did not typically affect an ADC's cytotoxicity to targeted cells but did increase bystander killing activity. ADCs with the highest in vitro bystander killing were then evaluated in vivo in mice, where they displayed improved efficacy compared to previously described types of maytansinoid conjugates.

Synthesis of Highly Potent N-10 Amino-Linked DNA-Alkylating Indolinobenzodiazepine Antibody-Drug Conjugates (ADCs).

Indolinobenzodiazepine DNA alkylators (IGNs) are the cytotoxic payloads in antibody-drug conjugates (ADCs) currently undergoing Phase I clinical evaluation (IMGN779, IMGN632, and TAK164). These ADCs possess linkers that have been incorporated into a central substituted phenyl spacer. Here, we present an alternative strategy for the IGNs, linking through a carbamate at the readily available N-10 amine present in the monoimine containing dimer. As a result, we have designed a series of N-10 linked IGN ADCs with a wide range of in vitro potency and tolerability, which may allow us to better match an IGN with a particular target based on the potential dosing needs.

Design, synthesis and evaluation of novel, potent DNA alkylating agents and their antibody-drug conjugates (ADCs).

Antibody-drug conjugates (ADCs) incorporating potent indolinobenzodiazepine (IGN) DNA alkylators as the cytotoxic payload are currently undergoing clinical evaluation. The optimized design of these payloads consists of an unsymmetrical dimer possessing both an imine and an amine effectively eliminating DNA crosslinking and demonstrating improved tolerability in mice. Here we present an alternate approach to generating DNA alkylating ADCs by linking the IGN monomer with a biaryl system which has a high DNA binding affinity to potentially enhance tolerability. These BIA ADCs were found to be highly cytotoxic in vitro and demonstrated potent antitumor activity in vivo.

Second brazilian consensus on the treatment of advanced prostate cancer: a SBOC-SBU-SBRT panel review

ABSTRACT Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The first Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.

Second brazilian consensus on the treatment of advanced prostate cancer - a SBOC-SBU-SBRT panel review.

Prostate cancer is the second most common cancer and the fi fth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The fi rst Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.

Dementia and Challenging Behaviors in Gerontological Centers. A Case Report.

Among the main challenges in geriatric and gerontological centers, we consider, central, the individualized attention to those elderly persons with challenging behaviors, to the extent that it is possible to design preventive strategies that delay cognitive deterioration and minimize consequences of behavior disorders. The first step will be to develop the correct interpretation of symptoms and deficits as a guarantee of a correct diagnosis which, in addition to not always being easy, has to be adapted to the progression of the disease. We present the case of a 68-year-old institutionalized individual, with an initial diagnosis of diffuse Lewy bodies dementia, analyzing his cognitive and behavioral evolution, and the pharmacological and non-pharmacological approach to the case.

Leveraging PET to image folate receptor α therapy of an antibody-drug conjugate.

BACKGROUND: The folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), IMGN853, shows great antitumor activity against FRα-expressing tumors in vivo, but patient selection and consequently therapy outcome are based on immunohistochemistry. The aim of this study is to develop an antibody-derived immuno-PET imaging agent strategy for targeting FRα in ovarian cancer as a predictor of treatment success. METHODS: We developed [89Zr]Zr-DFO-M9346A, a humanized antibody-based radiotracer targeting tumor-associated FRα in the preclinical setting. [89Zr]Zr-DFO-M9346A's binding ability was tested in an in vitro uptake assay using cell lines with varying FRα expression levels. The diagnostic potential of [89Zr]Zr-M9346A was evaluated in KB and OV90 subcutaneous xenografts. Following intravenous injection of [89Zr]Zr-DFO-M9346A (~90 µCi, 50 µg), PET imaging and biodistribution studies were performed. We determined the blood half-life of [89Zr]Zr-DFO-M9346A and compared it to the therapeutic, radioiodinated ADC [131I]-IMGN853. Finally, in vivo studies using IMG853 as a therapeutic, paired with [89Zr]Zr-DFO-M9346A as a companion diagnostic were performed using OV90 xenografts. RESULTS: DFO-M9346A was labeled with Zr-89 at 37 °C within 60 min and isolated in labeling yields of 85.7 ± 5.7%, radiochemical purities of 98.0 ± 0.7%, and specific activities of 3.08 ± 0.43 mCi/mg. We observed high specificity for binding FRα positive cells in vitro. For PET and biodistribution studies, [89Zr]Zr-M9346A displayed remarkable in vivo performance in terms of excellent tumor uptake for KB and OV xenografts (45.8 ± 29.0 %IA/g and 26.1 ± 7.2 %IA/g), with low non-target tissue uptake in other organs such as kidneys (4.5 ± 1.2 %IA/g and 4.3 ± 0.7 %IA/g). A direct comparison of the blood half life of [89Zr]Zr-M9346A and [131I]-IMGN853 corroborated the equivalency of the radiopharmaceutical and the ADC, paving the way for a companion PET imaging study. CONCLUSIONS: We developed a new folate receptor-targeted 89Zr-labeled PET imaging agent with excellent pharmacokinetics in vivo. Good tumor uptake in subcutaneous KB and OV90 xenografts were obtained, and ADC therapy studies were performed with the precision predictor.