University of Wisconsin–Madison
Dr. Ravi Patel headshot

Ravi Patel, MD, PhD

Bentson Laboratory Research Fellow

Department of Human Oncology

I am a Bentson Radiation Oncology Research Fellow in the Department of Human Oncology. I have an MD and PhD in biomedical engineering from Case Western University. I am pursuing a career as physician-scientist and one day hope to have my own lab. I currently work in the Morris Lab, where I apply my expertise in mathematical modeling, drug delivery and in situ vaccination to a variety of research projects. One project looks at targeting metastatic disease through a combination of killing suppressive immune cells and using systemic immunotherapy agents. An exciting aspect about immunotherapy is that it could potentially work on a variety of cancers. Cancer has the ability to evade the immune system, so if we can figure out how to activate the immune system to recognize someone’s cancer, I think we can use those concepts on a wide variety of tumors.

Education

Resident, University Hospitals of Cleveland, Radiation Oncology (2016)

Intern, Akron General Medical Center, (2013)

MD, Case Western Reserve University, Medicine (2012)

PhD, Case Western Reserve University, Biomedical Engineering (2011)

MS, Case Western Reserve University, Biomedical Engineering (2008)

BSE, Case Western University, Tissue Engineering (2003)

Academic Appointments

Bentson Fellow, Human Oncology (2017)

Selected Honors and Awards

NEOMED Oral Presentation Award (2013)

CTSC Training Grant (2010–2012)

NIH MSTP Training Grant (2004–2010)

IMECE Student Paper Competition Finalist (2004)

Biomedical Engineering Research Award (2003)

REU NSF Fellowship (2002)

CWRU President's Scholarship (1999–2003)

Boards, Advisory Committees and Professional Organizations

ASTRO Corporate Relations Committee (2016–pres.)

American Brachytherapy Society (2015–pres.)

Radiological Society of North America (2012–pres.)

American Society of Radiation Oncology (2012–pres.)

American Association for Cancer Research (2012–pres.)

American College of Radiology (2012–pres.)

Low dose radiation to all sites of disease enhances abscopal responses in immunogically “cold” tumors that don’t normally respond to traditional cancer immunotherapy approaches.

The broad goal of my research focus is to utilize radiation therapy to immunomodulate a tumor microenvironment to enhance the efficacy of immunotherapy treatments in solid tumors. My focus is on translational research first in preclinical models to optimize dosing, timing and efficacy of combination treatments with the goal of translating these findings in the lab to early phase clinical trials in patients. I hope to use data that we gather in the laboratory setting to gain mechanistic insights into how radiation interacts with tumor cells as well as a patient’s immune system. My ultimate goal is to design treatments that will result in improved patient survival and eventual cures in cancer patients with metastatic disease.

Combining Immunotherapy with Molecular Targeted Radionuclide Agents for Therapeutic Benefit

Radiation has been shown to synergize with systemic checkpoint blockade and improve its efficacy in multiple preclinical cancer studies. However, as clinicians when we have tried to translate these results to the clinic to improve outcomes in patients, we have had much more mixed results. There are several explanations for these lackluster results, including increased heterogeneity in spontaneously occurring tumors as well as more difficult to treat bulky and widespread disease in real-life patients compared to small single site disease studied in preclinical models. One strategy to overcome these challenges is to deliver immunomodulatory radiation to all sites of disease in a patient with metastatic cancer. Therefore, we developed a collaborative project with Dr. Jamey Weichert’s laboratory in the Department of Radiology to develop a molecularly targeted radionuclide (MTRT) that can deliver low dose immunomodulatory radiation to all sites of disease in patients with metastatic cancer. This MTRT agent, NM600, can be chelated to several different radionuclides to tailor radiation dose rate and delivery to different types of tumors. Moreover this MTRT agent has selective uptake into almost all tumor types, including more than 70 human and mouse tumors that have been tested. Preclinical work that I have led has shown that 90Y-NM600 MTRT has selective uptake into tumors and can improve the efficacy of immune checkpoint blockade in models that do not normally respond to this therapy. We are looking forward to translating this therapy into the clinic to help improve outcomes in patients.

 

Identification and Characterization of a Novel Synergistic Interaction Between Radiation and the Immune Response to Immune Stimulatory Nanoparticles in Murine Tumor Models

Combination of radiation and innateimmunity stimulating nanoparticles is an area of significant research interest for in situ vaccination strategies. However, the potential interaction between radiation and the immune response to such nanoparticle therapies has not been thoroughly investigated. I am leading a collaborative project between the Morris Lab and Gong Lab in Biomedical Engineering to investigate a novel smart polymer particle that stimulates the innate immune system. This particle is composed of a bacterial membrane, toll-like receptor 9 agonist, and STING agonist that are combined to enhance uptake of cancer antigens into antigen presenting cells (APCs), activate APCs, and then prime adaptive immunity T-cells to create an anti-tumor effector immune response. Using intratumoral injection ofthese smart nanoparticles following local radiation we demonstrated an in situ tumor vaccination effect capable of augmenting tumor response rates in multiple preclinical tumor models.

 

  • Commentary: Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery
    Okoye CC, Patel RB, Sahgal A, Chang EL, Lo SS
    2018 Oct 08; :
  • Combining brachytherapy and immunotherapy to achieve in situ tumor vaccination: A review of cooperative mechanisms and clinical opportunities. Brachytherapy
    Patel RB, Baniel CC, Sriramaneni RN, Bradley K, Markovina S, Morris ZS
    2018 Aug 02; :
    • More

      As immunotherapies continue to emerge as a standard component of treatment for a variety of cancers, the imperative for testing these in combination with other standard cancer therapies grows. Radiation therapy may be a particularly well-suited partner for many immunotherapies. By modulating immune tolerance and functional immunogenicity at a targeted tumor site, radiation therapy may serve as a method of in situ tumor vaccination. In situ tumor vaccination is a therapeutic strategy that seeks to convert a patient's own tumor into a nidus for enhanced presentation of tumor-specific antigens in a way that will stimulate and diversify an antitumor T cell response. The mechanisms whereby radiation may impact immunotherapy are diverse and include its capacity to simultaneously elicit local inflammation, temporary local depletion of suppressive lymphocyte lineages, enhanced tumor cell susceptibility to immune response, and immunogenic tumor cell death. Emerging data suggest that each of these mechanisms may display a distinct dose-response profile, making it challenging to maximize each of these effects using external beam radiation. Conversely, the highly heterogenous and conformal dose distribution achieved with brachytherapy may be optimal for enhancing the immunogenic capacity of radiation at a tumor site while minimizing off-target antagonistic effects on peripheral immune cells. Here, we review the immunogenic effects of radiation, summarize the clinical rationale and data supporting the use of radiation together with immunotherapies, and discuss the rationale and urgent need for further preclinical and clinical investigation specifically of brachytherapy in combination with immunotherapies. Harnessing these immunomodulatory effects of brachytherapy may offer solutions to overcome obstacles to the efficacy of immunotherapies in immunologically "cold" tumors while potentiating greater response in the context of immunologically "hot" tumors.

      View details for PubMedID 30078541
  • Tobacco Mosaic Virus-Delivered Cisplatin Restores Efficacy in Platinum-Resistant Ovarian Cancer Cells. Mol Pharm
    Franke CE, Czapar AE, Patel RB, Steinmetz NF
    2017 Sep 19; :
    • More

      Platinum resistance in ovarian cancer is the major determinant of disease prognosis. Resistance can first appear at the onset of disease or develop in response to platinum-based chemotherapy. Due to poor response to alternate chemotherapies and lack of targeted therapies, there is an urgent clinical need for a new avenue toward treatment of platinum-resistant (PR) ovarian cancer. Nanoscale delivery systems hold potential to overcome resistance mechanisms. In this work, we present tobacco mosaic virus (TMV) as a nanocarrier for cisplatin for treatment of PR ovarian cancer cells. The TMV-cisplatin conjugate (TMV-cisPt) was synthesized using a charge-driven reaction that, like a classic click reaction, is simple and reliable for large-scale production. Up to ∼1900 cisPt were loaded per TMV-cisPt with biphasic release profiles characterized by a fast half-life (t1) of ∼1 h and slow half-life (t2) of ∼12 h independent of pH. Efficient cell uptake of TMV was observed when incubated with ovarian cancer cells, and TMV-cisPt demonstrated superior cytotoxicity and DNA double strand breakage (DSB) in platinum-sensitive (PS) and PR cancer cells when compared to free cisplatin. The cytotoxicity in PR ovarian cancer cells and overall lower effective dosage requirement makes TMV-cisPt a powerful candidate for improved ovarian cancer treatment strategies.

      View details for PubMedID 28926265
  • Transcriptional-mediated effects of radiation on the expression of immune susceptibility markers in melanoma. Radiother Oncol
    Werner LR, Kler JS, Gressett MM, Riegert M, Werner LK, Heinze CM, Kern JG, Abbariki M, Erbe AK, Patel RB, Sriramaneni RN, Harari PM, Morris ZS
    2017 09; 124 (3): 418-426
    • More

      BACKGROUND AND PURPOSE: We recently reported a time-sensitive, cooperative, anti-tumor effect elicited by radiation (RT) and intra-tumoral-immunocytokine injection in vivo. We hypothesized that RT triggers transcriptional-mediated changes in tumor expression of immune susceptibility markers at delayed time points, which may explain these previously observed time-dependent effects.

      MATERIALS AND METHODS: We examined the time course of changes in expression of immune susceptibility markers following in vitro or in vivo RT in B78 murine melanoma and A375 human melanoma using flow cytometry, immunoblotting, and qPCR.

      RESULTS: Flow cytometry and immunoblot revealed time-dependent increases in expression of death receptors and T cell co-stimulatory/co-inhibitory ligands following RT in murine and human melanoma. Using high-throughput qPCR, we observed comparable time courses of RT-induced transcriptional upregulation for multiple immune susceptibility markers. We confirmed analogous changes in B78 tumors irradiated in vivo. We observed upregulated expression of DNA damage response markers days prior to changes in immune markers, whereas phosphorylation of the STAT1 transcription factor occurred concurrently with changes following RT.

      CONCLUSION: This study highlights time-dependent, transcription-mediated changes in tumor immune susceptibility marker expression following RT. These findings may help in the design of strategies to optimize sequencing of RT and immunotherapy in translational and clinical studies.

      View details for PubMedID 28893414
  • Complications from Stereotactic Body Radiotherapy for Lung Cancer. Cancers (Basel)
    Kang KH, Okoye CC, Patel RB, Siva S, Biswas T, Ellis RJ, Yao M, Machtay M, Lo SS
    2015 Jun 15; 7 (2): 981-1004
    • More

      Stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage, node negative non-small cell lung cancer (NSCLC) in patients who are either medically inoperable or refuse surgical resection. SBRT has high local control rates and a favorable toxicity profile relative to other surgical and non-surgical approaches. Given the excellent tumor control rates and increasing utilization of SBRT, recent efforts have focused on limiting toxicity while expanding treatment to increasingly complex patients. We review toxicities from SBRT for lung cancer, including central airway, esophageal, vascular (e.g., aorta), lung parenchyma (e.g., radiation pneumonitis), and chest wall toxicities, as well as radiation-induced neuropathies (e.g., brachial plexus, vagus nerve and recurrent laryngeal nerve). We summarize patient-related, tumor-related, dosimetric characteristics of these toxicities, review published dose constraints, and propose strategies to reduce such complications.

      View details for PubMedID 26083933
  • Comparison of Ray Tracing and Monte Carlo Calculation Algorithms for Thoracic Spine Lesions Treated With CyberKnife-Based Stereotactic Body Radiation Therapy. Technol Cancer Res Treat
    Okoye CC, Patel RB, Hasan S, Podder T, Khouri A, Fabien J, Zhang Y, Dobbins D, Sohn JW, Yuan J, Yao M, Machtay M, Sloan AE, Miller J, Lo SS
    2016 Feb; 15 (1): 196-202
    • More

      Stereotactic body radiation therapy (SBRT) is an emerging technology for the treatment of spinal metastases, although the dosimetric impact of the calculation method on spinal dose distribution is unknown. This study attempts to determine whether CyberKnife (CK)-based SBRT using a Ray Tracing (RyTc) algorithm is comparable dosimetrically to that of Monte Carlo (MC) for thoracic spinal lesions. Our institutional CK-based SBRT database for thoracic spinal lesions was queried and a cohort was generated. Patients were planned using RyTc and MC algorithms using the same beam angles and monitor units. Dose-volume histograms of the planning target volume (PTV), spinal cord, esophagus, and skin were generated, and dosimetric parameters were compared. There were 37 patients in the cohort. The average percentage volume of PTV covered by the prescribed dose with RyTc and MC algorithms was 91.1% and 80.4%, respectively (P < .001). The difference in average maximum spinal cord dose between RyTc and MC plans was significant (1126 vs 1084 cGy, P = .004), with the MC dose ranging from 18.7% below to 13.8% above the corresponding RyTc dose. A small reduction in maximum skin dose was also noted (P = .017), although no difference was seen in maximum esophageal dose (P = .15). Only PTVs smaller than 27 cm(3) were found to correlate with large (>10%) changes in dose to 90% of the volume (P = .014), while no correlates with the average percentage volume of PTV covered by the prescribed dose were demonstrated. For thoracic spinal CK-based SBRT, RyTc computation may overestimate the MC calculated average percentage volume of PTV covered by the prescribed dose and have unpredictable effects on doses to organs at risk, particularly the spinal cord. In this setting, use of RyTc optimization should be limited and always verified with MC.

      View details for PubMedID 25633137
  • Noninvasive characterization of the effect of varying PLGA molecular weight blends on in situ forming implant behavior using ultrasound imaging. Theranostics
    Solorio L, Olear AM, Hamilton JI, Patel RB, Beiswenger AC, Wallace JE, Zhou H, Exner AA
    2012; 2 (11): 1064-77
    • More

      In situ forming implants (ISFIs) have shown promise in drug delivery applications due to their simple manufacturing and minimally invasive administration. Precise, reproducible control of drug release from ISFIs is essential to their successful clinical application. This study investigated the effect of varying the molar ratio of different molecular weight (Mw) poly(D,L-lactic-co-glycolic acid) (PLGA) polymers within a single implant on the release of a small Mw mock drug (sodium fluorescein) both in vitro and in vivo. Implants were formulated by dissolving three different PLGA Mw (15, 29, and 53 kDa), as well as three 1:1 molar ratio combinations of each PLGA Mw in 1-methyl-2-pyrrolidinone (NMP) with the mock drug fluorescein. Since implant morphology and microstructure during ISFI formation and degradation is a crucial determinant of implant performance, and the rate of phase inversion has been shown to have an effect on the implant microstructure, diagnostic ultrasound was used to noninvasively quantify the extent of phase inversion and swelling behavior in both environments. Implant erosion, degradation, as well as the in vitro and in vivo release profiles were also measured using standard techniques. A non-linear mathematical model was used to correlate the drug release behavior with polymer phase inversion, with all formulations yielding an R(2) value greater than 0.95. Ultrasound was also used to create a 3D image reconstruction of an implant over a 12 day span. In this study, swelling and phase inversion were shown to be inversely related to the polymer Mw with 53 kDa polymer implants increasing at an average rate of 9.4%/day compared with 18.6%/day in the case of the 15 kDa PLGA. Additionally the onset of erosion, complete phase inversion, and degradation facilitated release required 9 d for 53 kDa implants, while these same processes began 3 d after injection into PBS with the 15 kDa implants. It was also observed that PLGA blends generally had intermediate properties when compared to pure polymer formulations. However, release profiles from the blend formulations were governed by a more complex set of processes and were not simply averages of release profiles from the pure polymers preparations. This study demonstrated that implant properties such as phase inversion, swelling and drug release could be tailored to by altering the molar ratio of the polymers used in the depot formulation.

      View details for PubMedID 23227123
  • Advances in image-guided intratumoral drug delivery techniques. Ther Deliv
    Solorio L, Patel RB, Wu H, Krupka T, Exner AA
    2010 Aug; 1 (2): 307-22
    • More

      Image-guided drug delivery provides a means for treating a variety of diseases with minimal systemic involvement while concurrently monitoring treatment efficacy. These therapies are particularly useful to the field of interventional oncology, where elevation of tumor drug levels, reduction of systemic side effects and post-therapy assessment are essential. This review highlights three such image-guided procedures: transarterial chemoembolization, drug-eluting implants and convection-enhanced delivery. Advancements in medical imaging technology have resulted in a growing number of new applications, including image-guided drug delivery. This minimally invasive approach provides a comprehensive answer to many challenges with local drug delivery. Future evolution of imaging devices, image-acquisition techniques and multifunctional delivery agents will lead to a paradigm shift in patient care.

      View details for PubMedID 22816134
  • Differentiation of benign periablational enhancement from residual tumor following radio-frequency ablation using contrast-enhanced ultrasonography in a rat subcutaneous colon cancer model. Ultrasound Med Biol
    Wu H, Patel RB, Zheng Y, Solorio L, Krupka TM, Ziats NP, Haaga JR, Exner AA
    2012 Mar; 38 (3): 443-53
    • More

      Benign periablational enhancement (BPE) response to thermal injury is a barrier to early detection of residual tumor in contrast enhanced imaging after radio-frequency (RF) ablation. The objective of this study was to evaluate the role of quantitative of contrast-enhanced ultrasound (CEUS) in early differentiation of BPE from residual tumor in a BD-IX rat subcutaneous colon cancer model. A phantom study was first performed to test the validity of the perfusion parameters in predicting blood flow of two US contrast imaging modes-contrast harmonic imaging (CHI) and microflow imaging (MFI). To create a simple model of BPE, a peripheral portion of the tumor was ablated along with surrounding normal tissue, leaving part of the tumor untreated. First-pass dynamic enhancement (FPDE) and MFI scans of CEUS were performed before ablation and immediately, 1, 4 and 7 days after ablation. Time-intensity-curves in regions of BPE and residual tumor were fitted to the function y = A(1-exp[-β{t-t0}])+C, in which A, β, t0 and C represent blood volume, flow speed, time to start and baseline intensity, respectively. In the phantom study, positive linear correlations were noted between A, β, Aβ and contrast concentration, speed and flow rate, respectively, in both CHI and MFI. On CEUS images of the in vivo study, the unenhanced ablated zone was surrounded by BPE and irregular peripheral enhancement consistent with residual tumor. On days 0, 4 and 7, blood volume (A) in BPE was significantly higher than that in residual tumor in both FPDE imaging and MFI. Significantly greater blood flow (Aβ) was seen in BPE compared with residual tumor tissue in FPDE on day 7 and in MFI on day 4. The results of this study demonstrate that qualitative CEUS can be potentially used for early detection of viable tumor in post-ablation assessment.

      View details for PubMedID 22266229
  • Effect of injection site on in situ implant formation and drug release in vivo. J Control Release
    Patel RB, Solorio L, Wu H, Krupka T, Exner AA
    2010 Nov 01; 147 (3): 350-8
    • More

      In situ forming drug delivery implants offer an attractive alternative to pre-formed implant devices for local drug delivery due to their ability to deliver fragile drugs, simple manufacturing process, and less invasive placement. However, the clinical translation of these systems has been hampered, in part, by poor correlation between in vitro and in vivo drug release profiles. To better understand this effect, the behavior of poly(D,l-lactide-co-glycolide) (PLGA) in situ forming implants was examined in vitro and in vivo after subcutaneous injection as well as injection into necrotic, non-necrotic, and ablated tumor. Implant formation was quantified noninvasively using an ultrasound imaging technique. Drug release of a model drug agent, fluorescein, was correlated with phase inversion in different environments. Results demonstrated that burst drug release in vivo was greater than in vitro for all implant formulations. Drug release from implants in varying in vivo environments was fastest in ablated tumor followed by implants in non-necrotic tumor, in subcutaneous tissue, and finally in necrotic tumor tissue with 50% of the loading drug mass released in 0.7, 0.9, 9.7, and 12.7h respectively. Implants in stiffer ablated and non-necrotic tumor tissue showed much faster drug release than implants in more compliant subcutaneous and necrotic tumor environments. Finally, implant formation examined using ultrasound confirmed that in vivo the process of precipitation (phase inversion) was directly proportional to drug release. These findings suggest that not only is drug release dependent on implant formation but that external environmental effects, such as tissue mechanical properties, may explain the differences seen between in vivo and in vitro drug release from in situ forming implants.

      View details for PubMedID 20728486
  • Characterization of formulation parameters affecting low molecular weight drug release from in situ forming drug delivery systems. J Biomed Mater Res A
    Patel RB, Carlson AN, Solorio L, Exner AA
    2010 Aug; 94 (2): 476-84
    • More

      In situ forming implants (ISFI) have shown promise in delivering adjuvant chemotherapy following minimally invasive cancer therapies such as thermal ablation of tumors. Although ISFI systems have been thoroughly investigated for delivery of high molecular weight (Mw) therapeutics, little research has been conducted to optimize their design for delivery of low Mw drugs. This study examined the effect of varying the formulation components on the low Mw drug release profile from a ISFI consisting of poly(D,L-lactide-co-glycolide) (PLGA), fluorescein (model drug), and excipient dissolved in 1-methyl-2-pyrrolidinone (NMP). Effects of varying PLGA Mw, excipient concentration, and drug loading were studied. Additionally, solubility studies were conducted to determine the critical water concentration required for phase inversion. Results demonstrated that PLGA Mw was the most significant factor in modulating low Mw drug release from the ISFI systems. ISFI formulations comprised of a low Mw (16 kDa) PLGA showed a significantly (p < 0.05) lower burst release (after 24 h), 28.2 +/- 0.5%, compared with higher Mw PLGA (60 kDa), 55.1 +/- 3.1%. Critical water concentration studies also demonstrated that formulations with lower Mw PLGA had increased solubility in water and may thus require more time to phase invert and release the drug.

      View details for PubMedID 20186771
  • Noninvasive characterization of in situ forming implants using diagnostic ultrasound. J Control Release
    Solorio L, Babin BM, Patel RB, Mach J, Azar N, Exner AA
    2010 Apr 19; 143 (2): 183-90
    • More

      In situ forming drug delivery systems provide a means by which a controlled release depot can be physically inserted into a target site without the use of surgery. The release rate of drugs from these systems is often related to the rate of implant formation. Currently, only a limited number of techniques are available to monitor phase inversion, and none of these methods can be used to visualize the process directly and noninvasively. In this study, diagnostic ultrasound was used to visualize and quantify the process of implant formation in a phase inversion based system both in vitro and in vivo. Concurrently, sodium fluorescein was used as a mock drug to evaluate the drug release profiles and correlate drug release and implant formation processes. Implants comprised of three different molecular weight poly(lactic-co-glycolic acid) (PLGA) polymers dissolved in 1-methyl-2-pyrrolidinone (NMP) were studied in vitro and a 29 kDa PLGA solution was evaluated in vivo. The implants were encapsulated in a 1% agarose tissue phantom for five days, or injected into a rat subcutaneously and evaluated for 48 h. Quantitative measurements of the gray-scale value (corresponding to the rate of implant formation), swelling, and precipitation were evaluated using image analysis techniques, showing that polymer molecular weight has a considerable effect on the swelling and formation of the in situ drug delivery depots. A linear correlation was also seen between the in vivo release and depot formation (R(2)=0.93). This study demonstrates, for the first time, that ultrasound can be used to noninvasively and nondestructively monitor and evaluate the phase inversion process of in situ forming drug delivery implants, and that the formation process can be directly related to the initial phase of drug release dependent on this formation.

      View details for PubMedID 20060859
  • Model simulation and experimental validation of intratumoral chemotherapy using multiple polymer implants. Med Biol Eng Comput
    Weinberg BD, Patel RB, Wu H, Blanco E, Barnett CC, Exner AA, Saidel GM, Gao J
    2008 Oct; 46 (10): 1039-49
    • More

      Radiofrequency ablation has emerged as a minimally invasive option for liver cancer treatment, but local tumor recurrence is common. To eliminate residual tumor cells in the ablated tumor, biodegradable polymer millirods have been designed for local drug (e.g., doxorubicin) delivery. A limitation of this method has been the extent of drug penetration into the tumor (<5 mm), especially in the peripheral tumor rim where thermal ablation is less effective. To provide drug concentration above the therapeutic level as needed throughout a large tumor, implant strategies with multiple millirods were devised using a computational model. This dynamic, 3-D mass balance model of drug distribution in tissue was used to simulate the consequences of various numbers of implants in different locations. Experimental testing of model predictions was performed in a rabbit VX2 carcinoma model. This study demonstrates the value of multiple implants to provide therapeutic drug levels in large ablated tumors.

      View details for PubMedID 18523817
  • Modeling doxorubicin transport to improve intratumoral drug delivery to RF ablated tumors. J Control Release
    Weinberg BD, Patel RB, Exner AA, Saidel GM, Gao J
    2007 Dec 04; 124 (1-2): 11-9
    • More

      A mathematical model of drug transport provides an ideal strategy to optimize intratumoral drug delivery implants to supplement radiofrequency (RF) ablation for tumor treatment. To simulate doxorubicin transport in non-ablated and ablated liver tumors, a one-dimensional, cylindrically symmetric transport model was generated using a finite element method (FEM). Parameters of this model, the diffusion (D) and elimination (gamma) coefficients for doxorubicin, were estimated using drug distributions measured 4 and 8 days after placing biodegradable implants in non-ablated and ablated rabbit VX2 liver carcinomas. In non-ablated tumor, values of diffusion and elimination parameters were 25% and 94% lower than normal liver tissue, respectively. In ablated tumor, diffusion near the ablation center was 75% higher than non-ablated tumor but decreased to the non-ablated tumor value at the ablation periphery. Drug elimination in ablated tumor was zero for the first four days, but by day 8 returned to 98% of the value for non-ablated tumor. Three-dimensional (3-D) simulations of drug delivery from implants with and without RF thermal ablation underscore the benefit of using RF ablation to facilitate local drug distribution. This study demonstrates the use of computational modeling and optimal parameter estimation to predict local drug pharmacokinetics from intratumoral implants after ablation.

      View details for PubMedID 17900740

Contact Information

Ravi Patel, MD, PhD

600 Highland Avenue Madison,
K4/B100
Madison, WI 53792